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WO2025172692A1 - Sebetralstat à administrer par voie orale pour le traitement d'une attaque d'angioedème héréditaire - Google Patents

Sebetralstat à administrer par voie orale pour le traitement d'une attaque d'angioedème héréditaire

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Publication number
WO2025172692A1
WO2025172692A1 PCT/GB2025/050237 GB2025050237W WO2025172692A1 WO 2025172692 A1 WO2025172692 A1 WO 2025172692A1 GB 2025050237 W GB2025050237 W GB 2025050237W WO 2025172692 A1 WO2025172692 A1 WO 2025172692A1
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WO
WIPO (PCT)
Prior art keywords
attack
hae
dose
patient
sebetralstat
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/GB2025/050237
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English (en)
Inventor
Utpaul Kumar AUDHYA
Matthew Scott IVERSON
Michael David Smith
Christopher Martyn Yea
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Kalvista Pharmaceuticals Ltd
Original Assignee
Kalvista Pharmaceuticals Ltd
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Filing date
Publication date
Application filed by Kalvista Pharmaceuticals Ltd filed Critical Kalvista Pharmaceuticals Ltd
Publication of WO2025172692A1 publication Critical patent/WO2025172692A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/10—Antioedematous agents; Diuretics

Definitions

  • the present invention relates to treatments of hereditary angioedema (HAE).
  • HAE hereditary angioedema
  • the present invention provides on-demand treatments of hereditary angioedema (HAE) by orally administering a plasma kallikrein inhibitor to a patient in need thereof on-demand.
  • Inhibitors of plasma kallikrein have a number of therapeutic applications, particularly in the treatment of hereditary angioedema.
  • Plasma kallikrein (PKa) is a trypsin-like serine protease that can liberate kinins from kininogens (see K. D.
  • bradykinin 2 receptors B2R
  • B2R bradykinin 2 receptors
  • PKa is thought to play a role in a number of inflammatory disorders.
  • the major inhibitor of PKa is the serpin C1 esterase inhibitor (C1INH).
  • HAE-C1INH hereditary angioedema
  • Plasma from HAE patients have increased levels of cleaved HK, which indicates the generation of bradykinin (PLoS ONE 8(8): e74043. 2013).
  • Treatment with PKa inhibitors, (such as the approved medicinal products ecallantide, lanadelumab, and berotralstat) has been shown to effectively treat HAE- C1INH.
  • Hereditary angioedema is a rare inherited disorder characterised by recurrent acute attacks where fluids accumulate outside of the blood vessels, blocking the normal flow of blood or lymphatic fluid and causing rapid swelling of tissues such as in the hands, feet, limbs, face, intestinal tract, or airway. “Hereditary angioedema” can thus be defined as any disorder characterised by recurrent episodes of bradykinin-mediated angioedema (e.g. severe swelling) caused by an inherited dysfunction/fault/mutation.
  • HAE type 1 HAE type 2
  • HAE type 2 HAE with normal C1INH levels and function
  • HAE type 1 is caused by mutations in the SERPING1 gene that lead to reduced levels of C1INH in in the blood.
  • HAE type 2 is caused by mutations in the SERPING1 gene that lead to dysfunction of the C1INH in the blood.
  • HAE types 1 and 2 also called HAE-C1INH
  • the pathophysiology of HAE-nC1INH is heterogeneous and not fully understood.
  • HAE-nC1INH is less well-defined and the underlying genetic dysfunction/fault/mutation can sometimes remain unknown. What is known is that the cause of HAE-nC1INH is not related to reduced levels or dysfunction of the C1INH (in contrast to HAE types 1 and 2).
  • HAE-nC1INH can be diagnosed by reviewing the family history and noting that angioedema has been inherited from a previous generation (and thus it is hereditary angioedema).
  • HAE-nC1INH can also be diagnosed by determining that there is a dysfunction/fault/mutation in a gene other than those related to C1INH. For example, it has been reported that dysfunction/fault/mutation with plasminogen can cause HAE-nC1INH (see e.g. Veronez et al., Front Med (Lausanne).2019 Feb 21;6:28; or Recke et al., Clin Transl Allergy.2019 Feb 14;9:9.). It has also been reported that dysfunction/fault/mutation with F12 gene and Factor XII can cause HAE-nC1INH (see e.g.
  • HAE-UNK Hereditary angioedema with normal C1-INH with versus without specific F12 gene mutations. Allergy.2015 Aug;70(8):1004-12, Bork K et al.
  • HAE-nC1INH Acute HAE attacks (shortened to “HAE attacks”) normally progress through three key clinically distinct stages: an initial prodromal stage (that can typically last for up to 12 hours), followed by a swelling stage, and then an absorption stage. A majority of HAE attacks announce themselves with prodromal symptoms.
  • prodromes Two thirds of prodromes appeared less than 6 hours before a HAE attack and no prodromes occur more than 24 hours before a HAE attack (Magerl et al., Clinical and Experimental Dermatology 2014, 39, 298-303).
  • prodromal symptoms may start to be observed: a slight swelling (particularly affecting the face and neck), a typical type of abdominal pain, a typical reddening of the skin called "erythema marginatum".
  • An attack is fully developed when it has reached maximum swelling and maximum expression of pain (e.g. abdominal attack), discomfort (e.g. peripheral attack) or threat to life (e.g. laryngeal attack).
  • the subsequent time period to normalization is determined by the time it takes for the swelling to disappear and the liquid that has penetrated the tissues to be reabsorbed.
  • Synthetic and small molecule plasma kallikrein inhibitors have been described previously, for example by Garrett et al. ("Peptide aldehyde." J. Peptide Res.52, 62-71 (1998)), T. Griesbacher et al.
  • HAE can manifest in patients who present with a genetic deficiency or dysfunction in C1 esterase inhibitor.
  • C1 esterase inhibitor can be administered to normalise the deficiency or dysfunction in C1 esterase inhibitor.
  • Such treatments can be prophylactic (i.e.
  • Cinryze® and Haegarda® contain a C1 esterase inhibitor and are authorised to prevent acute HAE attacks (i.e. prophylactic treatment). Treatment with Cinryze® requires the preparation of a solution from a powder, which is then injected every 3 or 4 days. Similarly, treatment with Haegarda® requires the preparation of a solution from a powder, which is then injected twice a week.
  • Lanadelumab is a recombinant fully human IgG1 kappa light chain monoclonal antibody. Reported adverse reactions of treatment with lanadelumab include hypersensitivity, injection site pain, injection site erythema, and injection site bruising.
  • the authorised EMA label for Takhzyro® active substance lanadelumab states that it “is not intended for treatment of acute HAE attacks” and that “in case of a breakthrough HAE attack, individualized treatment should be initiated with an approved rescue medication”. Also, as injections, both of these treatments involve a high patient burden.
  • Berotralstat (BCX7353) has been approved in some countries for preventative treatment of HAE (not as an on-demand treatment), e.g.
  • ASP-634 An Oral Drug Candidate for Diabetic MacularEdema”, ARVO 2012 May 6th – May 9th, 2012, Fort Lauderdale, Florida, Presentation 2240
  • ASP-440 a benzamidine
  • absorption may be improved by creating a prodrug such as ASP-634.
  • prodrugs can suffer from several drawbacks, for example, poor chemical stability and potential toxicity from the inert carrier or from unexpected metabolites.
  • indole amides are claimed as compounds that might overcome problems associated with drugs possessing poor or inadequate ADME-tox and physicochemical properties although no inhibition against plasma kallikrein is presented or claimed (Griffioen et al., “Indole amide derivatives and related compounds for use in the treatment of neurodegenerative diseases”, WO2010142801).
  • Other plasma kallikrein inhibitors known in the art are generally small molecules, some of which include highly polar and ionisable functional groups, such as guanidines or amidines. Recently, plasma kallikrein inhibitors that do not feature guanidine or amidine functionalities have been reported. For example Brandl et al.
  • HAE attacks resolve faster and are shorter after early treatment (Maurer M et al. PLoS ONE 2013;8(2): e53773. doi:10.1371/journal.pone.0053773) and thus early intervention when an attack is expected, or ongoing, is essential to desirably manage the disease.
  • injectable therapies for on-demand treatment of HAE patients, and further patient confidence that oral on-demand therapies can replace injectable therapies would be desirable.
  • Patients must have confidence in any alternative (non-injectable) therapy if they are to move away from their current therapy to such alternative therapies.
  • HAE hereditary angioedema
  • HAE bradykinin-mediated angioedema caused by an inherited genetic dysfunction, fault, or mutation.
  • HAE includes at least HAE type 1, HAE type 2, and HAE with normal C1INH levels and function (HAE-nC1INH).
  • the patient is preferably a human.
  • HAE can affect patients of all ages. Accordingly, the human patient can be a child (ages 0 to less than 18 years) or an adult (18 years old or older).
  • the patient can have a predisposition to angioedema. Specifically, the patient can be aged 12 years and above. The patient can also be aged 2 years and above. The human patient can be aged between 2 and less than 18.
  • the human patient can be aged between 2 and less than 12.
  • the human patient can be aged between 12 and less than 18.
  • the patient can be at least 70 years old.
  • the “second treatment of the HAE attack” or “second treatment” is the administration of any dose of active pharmaceutical ingredient for treating an HAE attack on-demand that is not sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • the second treatment can be an existing HAE treatment.
  • the “second treatment” can be pdC1INH, rhC1INH, icatibant, conestat alfa (Ruconest®), or ecallantide.
  • “second treatment of an HAE attack” does not include prophylactic treatments of HAE.
  • the terms “second dose”, “third dose”, “fourth dose” and “further dose” refer to the administration of a dose of sebetralstat subsequent to the initial dose. “To resolve the attack” or “attack resolution”, unless specified otherwise, means that the HAE attack clears without the need for a further dose of sebetralstat or a second treatment.
  • the term “consecutive time points” when used in the context of “symptom relief” can mean an assessment separated by 30 mins (particularly within 0-4 hours after administration of the compound). “Consecutive time points” can also mean an assessment separated by 1 hour (particularly within 4- 12 hours after administration of the compound). “Consecutive time points” can also mean an assessment separated by 3 hours (particularly within 12-24 hours after administration of the compound).
  • ODT orodispersible tablet
  • An ODT is not a swallowable tablet, for instance a conventional swallowable tablet or capsule.
  • Description of the invention The efficacy data from the phase 3 study described in Example 4 confirm that treatment with sebetralstat reduces the time to beginning of symptom relief, reduces the time to a reduction in attack severity and achieves complete attack resolution. These results are statistically significant.
  • the efficacy data from the phase 3 study described in Example 4 report that sebetralstat treatment can be used across a wide range of attack locations and severities, including severe and very severe attacks, and including attacks of the neck and above, which can be life-threating types of attack. Further, the data described herein report that sebetralstat (a plasma kallikrein inhibitor) is effective in patients who are also being treated with a prophylactic HAE treatment (even when the prophylactic treatment is also a plasma kallikrein inhibitor).
  • sebetralstat a plasma kallikrein inhibitor
  • sebetralstat a plasma kallikrein inhibitor
  • a prophylactic HAE treatment even when the prophylactic treatment is also a plasma kallikrein inhibitor
  • the attack of the neck and above can be a facial attack (i.e., an attack of the face) and/or an attack of the tongue and/or an attack of the throat.
  • phase 3 results report that sebetralstat provided rapid symptom relief in a broad HAE population that reflects clinical practice, and was safe and well-tolerated with a safety profile comparable with placebo. These results can provide patients with further confidence that they are able to treat a wide range of HAE attacks, including the most extreme attacks.
  • Treatment of severe or worse HAE attacks As noted above, HAE is a rare and potentially life-threatening genetic condition that involves recurrent attacks of unpredictable and often debilitating swelling in various parts of the body, including the hands, feet, genitals, stomach, face and/or throat. Severe attacks can be life-threatening and therefore it is of paramount importance that any on-demand treatment is fast-acting and effective.
  • the invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale.
  • HAE attack is characterised as “severe” according to the PGI-S scale.
  • the HAE attack is characterised as “very severe” according to the PGI-S scale.
  • PGI-S is a known scale in the art (see e.g. Allergy Asthma Proc. 2018 Jan 1;39(1):74-80.
  • any of the treatments described herein can be for treating an HAE attack that is characterised as “severe” or above according to the PGI-S scale. Specific embodiments are as follows.
  • the invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale.
  • the HAE attack is characterised as “severe” according to the PGI-S scale.
  • the HAE attack is characterised as “very severe” according to the PGI-S scale.
  • the first dose is administered on-demand within 1 hour of recognition of a symptom of an acute HAE attack.
  • the second dose is administered between about 2 hours and about 6 hours (more specifically, between about 2 hours and about 5 hours, between about 2 hours and about 4 hours, between 2 hours and about 3 hours) after the first dose.
  • the second dose is administered about 3 hours after the first dose.
  • the invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose.
  • HAE hereditary angioedema
  • the invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • HAE hereditary angioedema
  • the invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose.
  • a fourth dose is not administered to the patient, e.g., where the first dose, second dose and third dose provide sufficient therapeutic effectiveness, for example, the attack can be resolved without administering a fourth dose to the patient.
  • the patient is administered a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • the fourth dose can be administered between about 2 hours and about 6 hours (more specifically, between about 2 hours and about 5 hours, between about 2 hours and about 4 hours, between 2 hours and about 3 hours) after the third dose.
  • the fourth dose can be administered about 3 hours after the third dose.
  • the invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is also being treated with a prophylactic treatment of HAE.
  • HAE attack is characterised as “severe” according to the PGI-S scale.
  • the HAE attack is characterised as “very severe” according to the PGI-S scale.
  • the prophylactic treatment of HAE can be a PKa binding agent, a bradykinin B2 receptor antagonist, a Factor XIIa (FXIIa) binding agent, or a C1INH replacement agent.
  • the prophylactic treatment of HAE can be a PKa binding agent, preferably a plasma kallikrein inhibitor.
  • the prophylactic treatment of HAE can be a bradykinin B2 receptor antagonist.
  • the prophylactic treatment of HAE can be a Factor XIIa (FXIIa) binding agent, preferably a FXIIa inhibitor.
  • the prophylactic treatment of HAE can be attenuated androgen.
  • the invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®).
  • the HAE attack is characterised as “severe” according to the PGI-S scale.
  • the HAE attack is characterised as “very severe” according to the PGI-S scale.
  • the invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is lanadelumab.
  • the HAE attack is characterised as “severe” according to the PGI-S scale.
  • the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, wherein the patient is also being treated with a prophylactic treatment of HAE and wherein the attack is resolved without administering a second dose to the patient.
  • HAE hereditary angioedema
  • the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant.
  • C1INH replacement therapy such as Cinryze®, Ruconest®, Berinert®, or Haegarda®
  • donidalorsen and deucrictibant.
  • the HAE attack is characterised as “severe” according to the PGI-S scale.
  • the HAE attack is characterised as “very severe” according to the PGI-S scale.
  • the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale.
  • the invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab and berotralstat, and wherein the attack is resolved without administering a second dose to the patient.
  • HAE hereditary angioedema
  • the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale.
  • the invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is lanadelumab, and wherein the attack is resolved without administering a second dose to the patient.
  • HAE hereditary angioedema
  • the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale.
  • the invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is berotralstat, and wherein the attack is resolved without administering a second dose to the patient.
  • HAE hereditary angioedema
  • the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale.
  • the invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is not also being treated with a prophylactic treatment of HAE.
  • HAE attack is characterised as “severe” according to the PGI-S scale.
  • the HAE attack is characterised as “very severe” according to the PGI-S scale.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is also being treated with a prophylactic treatment of HAE.
  • the HAE attack is characterised as “severe” according to the PGI-S scale.
  • the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale.
  • the invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is a plasma kallikrein inhibitor.
  • HAE hereditary angioedema
  • the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant.
  • the invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®).
  • HAE hereditary angioedema
  • the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale.
  • the invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is berotralstat.
  • HAE hereditary angioedema
  • the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale.
  • the invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the patient is not also being treated with a prophylactic treatment of HAE.
  • HAE hereditary angioedema
  • the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale. In any of the above embodiments, the HAE attack is selected from a laryngeal attack, an attack of the neck and above, an abdominal attack, a subcutaneous attack, an attack of the arms, an attack of the hands, an attack of the legs, an attack of the feet, an attack of the head, an attack of the face, an attack of the neck, an attack of the torso, and an attack of the genitals. In an embodiment, the HAE attack is a laryngeal attack. In an embodiment, the HAE attack is an attack of the neck and above.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale and wherein the HAE attack is a laryngeal attack.
  • HAE attack is characterised as “mild” according to the PGI-S scale.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale and wherein the HAE attack is a laryngeal attack.
  • HAE attack is characterised as “moderate” according to the PGI-S scale.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is a laryngeal attack, and wherein the attack is resolved without administering a second dose to the patient.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, wherein the HAE attack is a laryngeal attack, and wherein the attack is resolved without administering a second dose to the patient.
  • the HAE attack is characterised as “severe” according to the PGI-S scale.
  • the HAE attack is characterised as “very severe” according to the PGI-S scale.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale, wherein the HAE attack is a laryngeal attack, and wherein the attack is resolved without administering a second dose to the patient.
  • the HAE attack is characterised as “mild” according to the PGI-S scale.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the HAE attack is an abdominal attack.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the HAE attack is a subcutaneous attack.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the HAE attack is an attack of the neck and above but is not a laryngeal attack.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the HAE attack is a laryngeal attack.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, wherein the HAE attack is a laryngeal attack, and wherein the attack is resolved without administering a second dose to the patient.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale, wherein the HAE attack is a laryngeal attack, and wherein the attack is resolved without administering a second dose to the patient.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale, wherein the HAE attack is a laryngeal attack, and wherein the attack is resolved without administering a second dose to the patient.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the HAE attack is an abdominal attack.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the HAE attack is a subcutaneous attack.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale and wherein the HAE attack is an attack of the neck and above but is not a laryngeal attack.
  • HAE hereditary angioedema
  • any of the embodiments described above in relation to the treatment of severe or worse HAE attacks according to the invention can, where appropriate, be considered in combination with any of the embodiments described below in relation to the treatment of HAE attacks in patients on prophylactic treatment, dosing, the treatment of HAE attacks of the neck and above, specific combination therapies and drug-drug interactions. It is intended that any of the embodiments can be combined.
  • Treatment of HAE attacks in patients on prophylactic treatment As noted above, existing treatments of HAE are either administered on-demand or as a prophylactic. On-demand treatment is administered in response to a specific attack to lessen its severity e.g., at the first sign of attack symptoms.
  • Prophylactic treatment involves continuously and regularly taking treatment to reduce the likelihood of an attack occurring i.e. not in response to one specific attack.
  • the overarching goal of long-term prophylactic treatment is to achieve an attack-free status.
  • existing prophylactic treatments are generally not completely effective, with patients receiving prophylactic treatment still suffering from HAE attacks. This is demonstrated by the attack incidences data taken from patients on prophylactic treatment that are reported in Example 4 and in Figures 2 and 3. For this reason, it is generally recommended that HAE patients carry an on-demand treatment at all times even if they are on prophylactic treatment (such treatment can sometimes be called a “rescue treatment”).
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE.
  • HAE hereditary angioedema
  • the invention provides sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) for use in treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE.
  • the invention provides a prophylactic treatment of HAE for use in treating hereditary angioedema (HAE), wherein the patient is orally administered a first dose of 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) on-demand for treating an attack of HAE on-demand.
  • the invention provides sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) and a prophylactic treatment of HAE for use in treating hereditary angioedema (HAE) in a patient in need thereof comprising: administering the prophylactic treatment of HAE to the patient and orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) for treating an attack of HAE on-demand.
  • sebetralstat or a pharmaceutically acceptable salt and/or solvate thereof
  • sebetralstat and the prophylactic treatment of HAE can be administered simultaneously, separately or sequentially.
  • sebetralstat and the prophylactic treatment of HAE are not necessarily given at the same time, i.e., sebetralstat and the prophylactic treatment of HAE can be given at different times of the day. Indeed, this would be expected because a patient would typically take their prophylactic treatment at a particular time, whereas the on-demand treatment would be used as necessary upon recognition of a HAE attack.
  • the first dose can be administered on-demand within 1 hour of recognition of a symptom of an acute HAE attack.
  • the first dose is administered on-demand within about 50 minutes, within about 40 minutes, within about 30 minutes, within about 20 minutes, within about 10 minutes, within about 6 minutes, or within about 5 minutes of the symptom of an acute HAE attack being recognised.
  • a second dose is not administered to the patient, e.g., where the first dose provides sufficient therapeutic effectiveness, for example, the attack can be resolved without administering a second dose to the patient.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • HAE hereditary angioedema
  • the second dose is administered between about 2 hours and about 6 hours (more specifically, between about 2 hours and about 5 hours, between about 2 hours and about 4 hours, between 2 hours and about 3 hours) after the first dose.
  • the second dose is administered about 3 hours after the first dose.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • HAE hereditary angioedema
  • a fourth dose is not administered to the patient, e.g., where the first dose, second dose and third dose provide sufficient therapeutic effectiveness, for example, the attack is resolved without administering a fourth dose to the patient.
  • the patient is administered a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • the fourth dose can be administered between about 2 hours and about 6 hours (more specifically, between about 2 hours and about 5 hours, between about 2 hours and about 4 hours, between 2 hours and about 3 hours) after the third dose.
  • the fourth dose can be administered about 3 hours after the third dose.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered
  • the prophylactic treatment of HAE can be a bradykinin B2 receptor antagonist.
  • the prophylactic treatment of HAE can be a Factor XIIa (FXIIa) binding agent, preferably a FXIIa inhibitor.
  • the prophylactic treatment of HAE can be attenuated androgen.
  • the attenuated androgen can be danazol or oxandrolone.
  • the prophylactic treatment of HAE can be tranexamic acid.
  • the prophylactic treatment of HAE can be non-androgen therapy.
  • the prophylactic treatment can be Cinryze®, Haegarda®, or Berinert®.
  • the prophylactic treatment can be lanadelumab or berotralstat.
  • the prophylactic treatment can be lanadelumab.
  • the prophylactic treatment can be berotralstat.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is a Factor XIIa (FXIIa) inhibitor.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the prophylactic treatment is a Factor XIIa (FXIIa) inhibitor.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the prophylactic treatment is a Factor XIIa (FXIIa) inhibitor.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the prophylactic treatment is a Factor XIIa (FXIIa) inhibitor.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the prophylactic treatment
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the prophylactic treatment is a Factor XIIa (FXIIa) inhibitor.
  • FXIIa Factor
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is a plasma kallikrein inhibitor.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the prophylactic treatment is a plasma kallikrein inhibitor.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the prophylactic treatment is a plasma kallikrein inhibitor.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the prophylactic treatment is a plasma kallikrein inhibitor.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the prophylactic treatment
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the prophylactic treatment is a plasma kallikrein inhibitor.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant.
  • HAE hereditary angioedema
  • the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant.
  • C1INH replacement therapy such as Cinryze®, Ruconest®, Berinert®, or Haegarda®
  • donidalorsen and deucrictibant.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the prophylactic treatment is selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant.
  • HAE hereditary angioedema
  • the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant.
  • C1INH replacement therapy such as Cinryze®, Ruconest®, Berinert®, or Haegarda®
  • donidalorsen and deucrictibant.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the prophylactic treatment is selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donida
  • the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant.
  • C1INH replacement therapy such as Cinryze®, Ruconest®, Berinert®, or Haegarda®
  • donidalorsen and deucrictibant.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the prophylactic treatment is selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), doni
  • the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant.
  • C1INH replacement therapy such as Cinryze®, Ruconest®, Berinert®, or Haegarda®
  • donidalorsen and deucrictibant.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the prophylactic treatment
  • the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant.
  • C1INH replacement therapy such as Cinryze®, Ruconest®, Berinert®, or Haegarda®
  • donidalorsen and deucrictibant.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the prophylactic treatment is selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C
  • the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant.
  • C1INH replacement therapy such as Cinryze®, Ruconest®, Berinert®, or Haegarda®
  • donidalorsen and deucrictibant.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered
  • the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant.
  • C1INH replacement therapy such as Cinryze®, Ruconest®, Berinert®, or Haegarda®
  • donidalorsen and deucrictibant.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®).
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®).
  • C1INH replacement therapy such as Cinryze®, Ruconest®, Berinert®, or Haegarda®
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®).
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®).
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the prophylactic treatment
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab and berotralstat.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the prophylactic treatment is selected from lanadelumab and berotralstat.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the prophylactic treatment is selected from lanadelumab and berotralstat.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the prophylactic treatment is selected from lanadelumab and berotralstat.
  • sebetralstat or a pharmaceutically acceptable salt and/or solvate thereof
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the prophylactic treatment
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the prophylactic treatment is selected from lanadelumab and berotralstat.
  • sebetralstat or a pharmaceutically acceptable salt and
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is lanadelumab.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the prophylactic treatment is lanadelumab.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the prophylactic treatment is lanadelumab.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the prophylactic treatment is lanadelumab.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the prophylactic treatment
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the prophylactic treatment is lanadelumab.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is berotralstat.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the prophylactic treatment is berotralstat.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the prophylactic treatment is berotralstat.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the prophylactic treatment is berotralstat.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the prophylactic treatment is berotralstat.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®).
  • C1INH replacement therapy such as Cinryze®, Ruconest®, Berinert®, or Haegarda®
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the prophylactic treatment is C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®).
  • C1INH replacement therapy such as Cinryze®, Ruconest®, Berinert®, or Haegarda®
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the prophylactic treatment
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered
  • the HAE attack is selected from a laryngeal attack, an attack of the neck and above, an abdominal attack, a subcutaneous attack, an attack of the arms, an attack of the hands, an attack of the legs, an attack of the feet, an attack of the head, an attack of the face, an attack of the neck, an attack of the torso, and an attack of the genitals.
  • the HAE attack is a laryngeal attack.
  • the HAE attack is an attack of the neck and above.
  • the HAE attack is an attack of the neck and above but is not a laryngeal attack.
  • the HAE attack is an abdominal attack.
  • the HAE attack is a subcutaneous attack. In an embodiment, the HAE attack is an attack of the arms. In an embodiment, the HAE attack is an attack of the hands. In an embodiment, the HAE attack is an attack of the legs. In an embodiment, the HAE attack is an attack of the feet. In an embodiment, the HAE attack is an attack of the head. In an embodiment, the HAE attack is an attack of the face. In an embodiment, the HAE attack is an attack of the neck. In an embodiment, the HAE attack is an attack of the torso. In an embodiment, the HAE attack is an attack of the genitals.
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is a laryngeal attack.
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is a laryngeal attack.
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is berotralstat and wherein the HAE attack is a laryngeal attack.
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is lanadelumab and wherein the HAE attack is a laryngeal attack.
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®) and wherein the HAE attack is a laryngeal attack.
  • C1INH replacement therapy such as Cinryze®, Ruconest®, Berinert®, or Haegarda®
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the attack is resolved without administering a second dose to the patient.
  • the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®).
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is lanadelumab and wherein the attack is resolved without administering a second dose to the patient.
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®) and wherein the attack is resolved without administering a second dose to the patient.
  • C1INH replacement therapy such as Cinryze®, Ruconest®, Berinert®, or Haegarda®
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the attack is resolved without administering a second dose to the patient.
  • the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®).
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is berotralstat and wherein the attack is resolved without administering a second dose to the patient.
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®) and wherein the attack is resolved without administering a second dose to the patient.
  • C1INH replacement therapy such as Cinryze®, Ruconest®, Berinert®, or Haegarda®
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the HAE attack is a laryngeal attack, and wherein the attack is resolved without administering a second dose to the patient.
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is an attack of the neck and above.
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is an abdominal attack.
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is a subcutaneous attack.
  • the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®).
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is berotralstat and wherein the HAE attack is a subcutaneous attack.
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is lanadelumab and wherein the HAE attack is a subcutaneous attack.
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®) and wherein the HAE attack is a subcutaneous attack.
  • the HAE attack is characterised as “mild” or above according to the PGI-S scale.
  • the HAE attack is characterised as “mild” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “moderate” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “moderate” according to the PGI-S scale. Preferably, the HAE attack is characterised as “severe” or above according to the PGI-S scale. In particular, the HAE attack is characterised as “severe” or “very severe” according to the PGI-S scale.
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and the HAE attack is characterised as “mild” or above according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and the HAE attack is characterised as “mild” according to the PGI-S scale.
  • the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®).
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is berotralstat and the HAE attack is characterised as “mild” according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is lanadelumab and the HAE attack is characterised as “mild” according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®) and the HAE attack is characterised as “mild” according to the PGI-S scale.
  • C1INH replacement therapy such as Cinryze®, Ruconest®, Berinert®, or Haegarda®
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and the HAE attack is characterised as “moderate” or above according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and the HAE attack is characterised as “moderate” according to the PGI-S scale.
  • the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®).
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is berotralstat and the HAE attack is characterised as “moderate” according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is lanadelumab and the HAE attack is characterised as “moderate” according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®) and the HAE attack is characterised as “moderate” according to the PGI-S scale.
  • C1INH replacement therapy such as Cinryze®, Ruconest®, Berinert®, or Haegarda®
  • the invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale.
  • the HAE attack is characterised as “severe” according to the PGI-S scale.
  • the HAE attack is characterised as “very severe” according to the PGI-S scale.
  • the invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “mild” according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “moderate” according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale.
  • HAE hereditary angioedema
  • the HAE attack is characterised as “severe” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “very severe” according to the PGI-S scale.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale.
  • HAE hereditary angioedema
  • the HAE attack is characterised as “mild” according to the PGI-S scale.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale.
  • HAE hereditary angioedema
  • the HAE attack is characterised as “moderate” according to the PGI-S scale.
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the HAE attack is a laryngeal attack, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale.
  • the HAE attack is characterised as “severe” according to the PGI-S scale.
  • the HAE attack is characterised as “very severe” according to the PGI-S scale.
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the HAE attack is a laryngeal attack, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, and wherein the attack is resolved without administering a second dose to the patient.
  • HAE hereditary angioedema
  • the HAE attack is characterised as “mild” according to the PGI-S scale.
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the HAE attack is a laryngeal attack, wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale, and wherein the attack is resolved without administering a second dose to the patient.
  • HAE hereditary angioedema
  • the HAE attack is characterised as “mild” according to the PGI-S scale.
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the HAE attack is a laryngeal attack, and wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale.
  • the HAE attack is characterised as “moderate” according to the PGI-S scale.
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the HAE attack is a laryngeal attack, wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale, and wherein the attack is resolved without administering a second dose to the patient.
  • the HAE attack is characterised as “moderate” according to the PGI-S scale.
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the HAE attack is an attack of the neck and above, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale.
  • the HAE attack is characterised as “severe” according to the PGI-S scale.
  • the HAE attack is characterised as “very severe” according to the PGI-S scale.
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the HAE attack is an attack of the neck and above, and wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “mild” according to the PGI-S scale.
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the HAE attack is an attack of the neck and above, and wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “moderate” according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is an abdominal attack, and wherein the HAE attack is characterised as “severe” or above according to the PGI- S scale.
  • the HAE attack is characterised as “severe” according to the PGI-S scale.
  • the HAE attack is characterised as “very severe” according to the PGI-S scale.
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is an abdominal attack, and wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “mild” according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is an abdominal attack, and wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “moderate” according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is a subcutaneous attack, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale.
  • the HAE attack is characterised as “severe” according to the PGI-S scale.
  • the HAE attack is characterised as “very severe” according to the PGI-S scale.
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is a subcutaneous attack, and wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “mild” according to the PGI-S scale.
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is a subcutaneous attack, and wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “moderate” according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is an attack of the neck and above but is not a laryngeal attack, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “severe” according to the PGI-S scale.
  • the HAE attack is characterised as “very severe” according to the PGI-S scale. Dosing Given the serious nature of HAE attacks, and that they can increase in severity such that they can be life-threatening, it is important that any on-demand treatment provides reliably safe and effective treatment. The data in Example 4 further confirm that particular dosage regimens of sebetralstat provide such reliable treatment.
  • the invention therefore also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • HAE hereditary angioedema
  • the first dose is administered on-demand within about 50 minutes, within about 40 minutes, within about 30 minutes, within about 20 minutes, within about 10 minutes, within about 6 minutes, or within about 5 minutes of the symptom of an acute HAE attack being recognised.
  • the second dose is administered between about 2 hours and about 6 hours (more specifically, between about 2 hours and about 5 hours, between about 2 hours and about 4 hours, between 2 hours and about 3 hours) after the first dose.
  • the second dose is administered about 3 hours after the first dose.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose.
  • HAE hereditary angioedema
  • a third dose is not administered to the patient, e.g., where the first dose and second dose provide sufficient therapeutic effectiveness, for example, the attack can be resolved without administering a third dose to the patient.
  • the patient is administered a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • the third dose can be administered between about 2 hours and about 6 hours (more specifically, between about 2 hours and about 5 hours, between about 2 hours and about 4 hours, between 2 hours and about 3 hours) after the second dose.
  • the third dose can be administered about 3 hours after the second dose.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose.
  • HAE hereditary angioedema
  • a fourth dose is not administered to the patient, e.g., where the first dose, second dose and third dose provide sufficient therapeutic effectiveness, for example, the attack can be resolved without administering a fourth dose to the patient.
  • the patient is administered a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • the fourth dose can be administered between about 2 hours and about 6 hours (more specifically, between about 2 hours and about 5 hours, between about 2 hours and about 4 hours, between 2 hours and about 3 hours) after the third dose.
  • the fourth dose can be administered about 3 hours after the third dose.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the
  • no further dose is administered to the patient, e.g., the attack is resolved without administering any further dose to the patient, in particular, no fifth dose is administered.
  • each dose is preferably administered as one unit dose.
  • each unit dose is preferably administered as one tablet (e.g. a film-coated tablet or an orodispersible tablet).
  • the patient can also be being treated with a prophylactic treatment of HAE. Specific embodiments wherein the patient is also being treated with a prophylactic treatment of HAE are described above.
  • the prophylactic treatment of HAE can be a PKa binding agent, a bradykinin B2 receptor antagonist, a Factor XIIa (FXIIa) binding agent, or a C1INH replacement agent.
  • the prophylactic treatment of HAE can be a PKa binding agent, preferably a plasma kallikrein inhibitor.
  • the prophylactic treatment of HAE can be a bradykinin B2 receptor antagonist.
  • the prophylactic treatment of HAE can be a Factor XIIa (FXIIa) binding agent, preferably a FXIIa inhibitor.
  • the prophylactic treatment of HAE can be attenuated androgen.
  • the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant.
  • C1INH replacement therapy such as Cinryze®, Ruconest®, Berinert®, or Haegarda®
  • the prophylactic treatment of HAE is C1 inhibitor.
  • the prophylactic treatment can be Cinryze®, Haegarda®, or Berinert®.
  • the prophylactic treatment can be lanadelumab or berotralstat.
  • the prophylactic treatment can be lanadelumab.
  • the prophylactic treatment can be berotralstat.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is not also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is not also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is not also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is not also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose.
  • HAE hereditary an
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is not also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is not also being treated with a prophylactic treatment of HAE, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is
  • the HAE attack is selected from a laryngeal attack, an attack of the neck and above, an abdominal attack, a subcutaneous attack, an attack of the arms, an attack of the hands, an attack of the legs, an attack of the feet, an attack of the head, an attack of the face, an attack of the neck, an attack of the torso, and an attack of the genitals.
  • the HAE attack is a laryngeal attack.
  • the HAE attack is an attack of the neck and above.
  • the HAE attack is an attack of the neck and above but is not a laryngeal attack.
  • the HAE attack is an abdominal attack.
  • the HAE attack is a subcutaneous attack. In an embodiment, the HAE attack is an attack of the arms. In an embodiment, the HAE attack is an attack of the hands. In an embodiment, the HAE attack is an attack of the legs. In an embodiment, the HAE attack is an attack of the feet. In an embodiment, the HAE attack is an attack of the head. In an embodiment, the HAE attack is an attack of the face. In an embodiment, the HAE attack is an attack of the neck. In an embodiment, the HAE attack is an attack of the torso. In an embodiment, the HAE attack is an attack of the genitals.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the HAE attack is a laryngeal attack.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the HAE attack is an abdominal attack.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the HAE attack is a subcutaneous attack.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the HAE attack is a subcutaneous attack.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the HAE attack is an abdominal attack.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the HAE attack is a laryngeal attack.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the HAE attack is an abdominal attack.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the HAE attack is a subcutaneous attack.
  • HAE hereditary angioedema
  • the HAE attack is characterised as “mild” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “mild” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “moderate” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “moderate” according to the PGI-S scale. Preferably, the HAE attack is characterised as “severe” or above according to the PGI-S scale. In particular, the HAE attack is characterised as “severe” or “very severe” according to the PGI-S scale.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the HAE attack is characterised as “mild” according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the HAE attack is characterised as “moderate” according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the HAE attack is a laryngeal attack, and wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the HAE attack is an abdominal attack, and wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the HAE attack is a subcutaneous attack, and wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the HAE attack is a laryngeal attack, and wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the HAE attack is an abdominal attack, and wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the HAE attack is a subcutaneous attack, and wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the HAE attack is a laryngeal attack, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the HAE attack is an abdominal attack, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the HAE attack is a subcutaneous attack, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale.
  • HAE hereditary angioedema
  • any of the embodiments described above in relation to the treatment of severe or worse HAE attacks, treatment of HAE attacks in patients on prophylactic treatment, or dosing, or below in relation to specific combination therapies and drug-drug interactions can, where appropriate, be considered in combination with any of the embodiments described herein relation to treatment of HAE attacks of the neck and above. It is intended that any of the embodiments can be combined. Therefore, where appropriate, any of the treatments described herein can be for treating an HAE attack of the neck and above.
  • Specific embodiments are as follows. Specific treatments of HAE attacks of the neck and above The attack of the neck and above can be a facial attack (i.e., an attack of the face) and/or an attack of the tongue and/or an attack of the throat.
  • the attack of the neck and above can be a facial attack.
  • the attack of the neck and above can be an attack of the tongue.
  • the attack of the neck and above can be an attack of the throat.
  • the attack of the neck and above can be a laryngeal attack.
  • the attack of the neck and above can be an attack of the throat, and/or the tongue, and/or face.
  • the attack of the neck and above can be an attack of the tongue, and/or the throat, and/or face.
  • the attack of the neck and above can be an attack of the face, and/or the throat, and/or the throat.
  • the attack of the neck and above is an attack of the throat but is not a laryngeal attack.
  • the first dose can be administered on-demand within 1 hour of recognition of a symptom of an acute HAE attack. In another embodiment, the first dose is administered on-demand within about 50 minutes, within about 40 minutes, within about 30 minutes, within about 20 minutes, within about 10 minutes, within about 6 minutes, or within about 5 minutes of the symptom of an acute HAE attack being recognised.
  • a second dose is not administered to the patient, e.g., where the first dose provides sufficient therapeutic effectiveness, for example, the attack can be resolved without administering a second dose to the patient.
  • the attack of the neck and above is a laryngeal attack and the attack is resolved without administering a second dose to the patient.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • HAE hereditary angioedema
  • the second dose is administered between about 2 hours and about 6 hours (more specifically, between about 2 hours and about 5 hours, between about 2 hours and about 4 hours, between 2 hours and about 3 hours) after the first dose.
  • the second dose is administered about 3 hours after the first dose.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose.
  • HAE hereditary angioedema
  • a third dose is not administered to the patient, e.g., where the first dose and second dose provide sufficient therapeutic effectiveness, for example, the attack can be resolved without administering a third dose to the patient.
  • the patient is administered a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • the third dose can be administered between about 2 hours and about 6 hours (more specifically, between about 2 hours and about 5 hours, between about 2 hours and about 4 hours, between 2 hours and about 3 hours) after the second dose.
  • the third dose can be administered about 3 hours after the second dose.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose.
  • HAE hereditary angioedema
  • a fourth dose is not administered to the patient, e.g., where the first dose, second dose and third dose provide sufficient therapeutic effectiveness, for example, the attack can be resolved without administering a fourth dose to the patient.
  • the patient is administered a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • the fourth dose can be administered between about 2 hours and about 6 hours (more specifically, between about 2 hours and about 5 hours, between about 2 hours and about 4 hours, between 2 hours and about 3 hours) after the third dose.
  • the fourth dose can be administered about 3 hours after the third dose.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours
  • each dose is preferably administered as one unit dose.
  • each unit dose is preferably administered as one tablet (e.g. a film-coated tablet or an orodispersible tablet).
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is also being treated with a prophylactic treatment of HAE.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the patient is also being treated with a prophylactic treatment of HAE.
  • HAE hereditary angioedema
  • the prophylactic treatment of HAE can be a PKa binding agent, a bradykinin B2 receptor antagonist, a Factor XIIa (FXIIa) binding agent, or a C1INH replacement agent.
  • the prophylactic treatment of HAE can be a PKa binding agent, preferably a plasma kallikrein inhibitor.
  • the prophylactic treatment of HAE can be a bradykinin B2 receptor antagonist.
  • the prophylactic treatment of HAE can be a Factor XIIa (FXIIa) binding agent, preferably a FXIIa inhibitor.
  • the prophylactic treatment of HAE can be attenuated androgen.
  • the attenuated androgen can be danazol or oxandrolone.
  • the prophylactic treatment of HAE can be tranexamic acid.
  • the prophylactic treatment of HAE can be non-androgen therapy.
  • the prophylactic treatment of HAE can be selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant.
  • the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant.
  • C1INH replacement therapy such as Cinryze®, Ruconest®, Berinert®, or Haegarda®
  • the prophylactic treatment of HAE is C1 inhibitor.
  • the prophylactic treatment can be Cinryze®, Haegarda®, or Berinert®.
  • the prophylactic treatment can be lanadelumab or berotralstat.
  • the prophylactic treatment can be lanadelumab.
  • the prophylactic treatment can be berotralstat.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is a plasma kallikrein inhibitor.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is a plasma kallikrein inhibitor.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is a plasma kallikrein inhibitor.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant.
  • HAE hereditary angioedema
  • the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant.
  • C1INH replacement therapy such as Cinryze®, Ruconest®, Berinert®, or Haegarda®
  • donidalorsen and deucrictibant.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant.
  • the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant.
  • C1INH replacement therapy such as Cinryze®, Ruconest®, Berinert®, or Haegarda®
  • donidalorsen and deucrictibant.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Ber
  • the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant.
  • C1INH replacement therapy such as Cinryze®, Ruconest®, Berinert®, or Haegarda®
  • donidalorsen and deucrictibant.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®).
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®).
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®).
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab and berotralstat.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab and berotralstat.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is selected from lanadelumab and berotralstat.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is lanadelumab.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is lanadelumab.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is lanadelumab.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is berotralstat.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is berotralstat.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is berotralstat.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®).
  • C1INH replacement therapy such as Cinryze®, Ruconest®, Berinert®, or Haegarda®
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®).
  • C1INH replacement therapy such as Cinryze®, Ruconest®, Berinert®, or Haegarda®
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the patient is also being treated with a prophylactic treatment of HAE, wherein the prophylactic treatment is C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®).
  • C1INH replacement therapy such as Cinryze®, Ru
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is not also being treated with a prophylactic treatment of HAE.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the patient is not also being treated with a prophylactic treatment of HAE.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the patient is not also being treated with a prophylactic treatment of HAE.
  • HAE hereditary angioedema
  • the HAE attack is characterised as “mild” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “mild” according to the PGI-S scale. In another embodiment, the HAE attack is characterised as “moderate” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “moderate” according to the PGI-S scale. Preferably, the HAE attack is characterised as “severe” or above according to the PGI-S scale. In particular, the HAE attack is characterised as “severe” or “very severe” according to the PGI-S scale.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the HAE attack is characterised as “mild” or above according to the PGI- S scale.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the attack of the neck and above is not a laryngeal attack.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the attack of the neck and above is not a laryngeal attack.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, and wherein the attack of the neck and above is not a laryngeal attack.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the attack of the neck and above is not a laryngeal attack.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours and about 6 hours after the second dose, preferably about 3 hours after the second dose, and wherein the attack of the neck and above is not a laryn
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and wherein the attack of the neck and above is not a laryngeal attack.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the HAE attack is an attack of the neck and above, and wherein the patient is administered a first dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a second dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) followed by a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), wherein the second dose is administered between about 2 hours and about 6 hours after the first dose, preferably about 3 hours after the first dose, wherein the third dose is administered between about 2 hours
  • sebetralstat or a pharmaceutically acceptable salt and/or solvate thereof
  • sebetralstat or a pharmaceutically acceptable salt and/or solvate thereof
  • the attack of the neck and above prevents the attack from progressing into a laryngeal attack.
  • sebetralstat a plasma kallikrein inhibitor
  • sebetralstat a plasma kallikrein inhibitor
  • a prophylactic HAE treatment even when the prophylactic treatment is also a plasma kallikrein inhibitor
  • the HAE attack is a severe or very severe attack and/or where the HAE attack is an attack of the neck and above but is not a laryngeal attack.
  • the attack of the neck and above can be a facial attack (i.e., an attack of the face) and/or an attack of the tongue and/or an attack of the throat. It is important that a broad range of HAE patients and a wide range of HAE attacks can benefit from on-demand treatment.
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is an attack of the neck and above but is not a laryngeal attack.
  • HAE hereditary angioedema
  • the attack of the neck and above can be a facial attack and/or an attack of the throat and/or an attack of the tongue.
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “severe” according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “very severe” according to the PGI-S scale.
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, and wherein the HAE attack is selected from a laryngeal attack, an attack of the neck and above, an abdominal attack, and a subcutaneous attack.
  • the HAE attack can be a laryngeal attack.
  • the HAE attack can be an attack of the neck and above.
  • the HAE attack can be an abdominal attack.
  • the HAE attack can be a subcutaneous attack.
  • the HAE attack is characterised as “moderate” or above according to the PGI-S scale. In an embodiment, the HAE attack is characterised as “moderate” according to the PGI-S scale. Preferably, the HAE attack is characterised as “severe” or above according to the PGI-S scale. In particular, the HAE attack is characterised as “severe” or “very severe” according to the PGI-S scale.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is an attack of the neck and above but is not a laryngeal attack, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale.
  • the prophylactic treatment of HAE can be a PKa binding agent, a bradykinin B2 receptor antagonist, a Factor XIIa (FXIIa) binding agent, or a C1INH replacement agent.
  • the prophylactic treatment of HAE can be a PKa binding agent, preferably a plasma kallikrein inhibitor.
  • the data in Example 4 show that sebetralstat (a plasma kallikrein inhibitor) is safe and effective at treating HAE attacks even when the patient is already taking a different plasma kallikrein inhibitor as a prophylactic treatment (specifically, lanadelumab or berotralstat). This is advantageous and demonstrates the usefulness and a reliability of sebetralstat (a plasma kallikrein inhibitor) in a wide range of relevant clinical circumstances e.g. even when a patient is taking a plasma kallikrein inhibitor prophylactic treatment.
  • the prophylactic treatment of HAE can be a bradykinin B2 receptor antagonist.
  • the prophylactic treatment of HAE can be a Factor XIIa (FXIIa) binding agent, preferably a FXIIa inhibitor.
  • the prophylactic treatment of HAE can be attenuated androgen.
  • the attenuated androgen can be danazol or oxandrolone.
  • the prophylactic treatment of HAE can be tranexamic acid.
  • the prophylactic treatment of HAE can be non-androgen therapy.
  • the prophylactic treatment can be Cinryze®, Haegarda®, or Berinert®.
  • the prophylactic treatment can be lanadelumab or berotralstat.
  • the prophylactic treatment can be lanadelumab.
  • the prophylactic treatment can be berotralstat.
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, wherein the prophylactic treatment is a Factor XIIa (FXIIa) inhibitor.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is an attack of the neck and above but is not a laryngeal attack, wherein the prophylactic treatment is a Factor XIIa (FXIIa) inhibitor.
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, wherein the prophylactic treatment is a plasma kallikrein inhibitor.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is an attack of the neck and above but is not a laryngeal attack, wherein the prophylactic treatment is a plasma kallikrein inhibitor.
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, wherein the prophylactic treatment is selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is an attack of the neck and above but is not a laryngeal attack, wherein the prophylactic treatment is selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant.
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, wherein the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®).
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is an attack of the neck and above but is not a laryngeal attack, wherein the prophylactic treatment is selected from lanadelumab, berotralstat, and C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®).
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, wherein the prophylactic treatment is selected from lanadelumab and berotralstat.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is an attack of the neck and above but is not a laryngeal attack, wherein the prophylactic treatment is selected from lanadelumab and berotralstat.
  • HAE hereditary angioedema
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale, wherein the prophylactic treatment is lanadelumab.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is an attack of the neck and above but is not a laryngeal attack, wherein the prophylactic treatment is lanadelumab.
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is an attack of the neck and above but is not a laryngeal attack, wherein the prophylactic treatment is C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®).
  • C1INH replacement therapy such as Cinryze®, Ruconest®, Berinert®, or Haegarda®
  • Drug-drug interactions demonstrate that a drug-drug interaction occurs when sebetralstat (or pharmaceutically acceptable salt and/or solvate thereof) is administered with a strong or moderate CYP3A4 inhibitor or a CYP3A4 inducer.
  • concomitant administration of a strong or moderate CYP3A4 inhibitor or a strong or moderate CYP3A4 inducer affects the blood levels of sebetralstat (or pharmaceutically acceptable salt and/or solvate thereof).
  • Concomitant administration of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) and a CYP3A4 inhibitor has the potential to increase or prolong the effects of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • the invention therefore provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient has taken, or will take, a concomitant dose of a strong or moderate CYP3A4 inhibitor and wherein the method comprises reducing the normal dose of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • HAE hereditary angioedema
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient has taken, or will take, a concomitant dose of a strong or moderate CYP3A4 inducer and wherein the method comprises increasing the normal dose of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • HAE hereditary angioedema
  • sebetralstat and the CYP3A4 inhibitor/inducer are not necessarily given at the same time, i.e., sebetralstat and the CYP3A4 inhibitor/inducer can be given at different times of the day.
  • a “strong CYP3A4 inhibitor” is a drug that increases the AUC of sensitive index substrates of a given metabolic pathway ⁇ 5-fold.
  • a “moderate CYP3A4 inhibitor” is a drug that increases the AUC of sensitive index substrates of a given metabolic pathway by ⁇ 2- to ⁇ 5-fold.
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient has taken, or will take, a concomitant dose of a strong or moderate CYP3A4 inhibitor and wherein the method comprises reducing the normal dose of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) so as to diminish the additive effect experienced when co-administered with the strong or moderate CYP3A4 inhibitor.
  • HAE hereditary angioedema
  • the additive effect is an increased therapeutic effect of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • the dose of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) is reduced by about 10% to about 60% of the normal dose for the patient.
  • the dose of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) is reduced by about 20% to about 50% of the normal dose for the patient.
  • the dose of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) is reduced by about 30% to about 50% of the normal dose for the patient.
  • the strong CYP3A4 inhibitor can be selected from itraconazole, ketoconazole, ritonavir, elvitegravir and ritonavir, indinavir and ritonavir, lopinavir and ritonavir, clarithromycin, ceritinib, cobicistat, idelalisib, nefazodone, nelfinavir, paritaprevir and ritonavir and (ombitasvir and/or dasabuvir), posaconazole, saquinavir and ritonavir, telithromycin, tipranavir and ritonavir, voriconazole, darunavir , telaprevir, stiripentol, curcumin, troleandomycin, atazanavir, naloxone, nilotinib, delavirdine, loperamide, ribociclib, danoprevir,
  • the CYP3A4 inhibitor is a moderate CYP3A4 inhibitor.
  • the moderate CYP3A4 inhibitor can be selected from verapamil, aprepitant, ciprofloxacin, conivaptan, crizotinib, diltiazem, dronedarone, erythromycin, fluconazole, grapefruit juice, imatinib, isavuconazole, isavuconazonium, luliconazole, netupitant, miconazole, nicardipine, isoniazid, danazol, lovastatin, ziprasidone, desvenlafaxine, indalpine, zimelidine, milnacipran, fusidic acid, barnidipine, benidipine, isradipine, haloperidol, linagliptin, fosnetupitant, simeprevir, nilvadipine, primaquine, clozapine, ti
  • the invention also provides a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient has taken, or will take, a concomitant dose of a strong or moderate CYP3A4 inducer and wherein the method comprises increasing the normal dose of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) so as to compensate for the effect experienced during co-administration.
  • the effect experienced during co-administration is a decreased therapeutic effect of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • the dose of sebetralstat is increased by about 50% of the normal dose for the patient.
  • the “normal dose” for the patient is preferably 300mg.
  • the CYP3A4 inducer is a strong CYP3A4 inducer.
  • the strong CYP3A4 inducer can be selected from 3-phenytoin, fosphenytoin, apalutamide, carbamazepine, enzalutamide, ivosidenib, lumacaftor and ivacaftor, mitotane, rifampin, St.
  • the moderate CYP3A4 inducer can be selected from efavirenz, bosentan, cenobamate, dabrafenib, etravirine, lorlatinib, pexidartinib, phenobarbital, primidone, sotorasib, modafinil, nafcillin, bexarotene, avasimibe, echinacea, dexamethasone, and dexamethasone acetate. Further embodiments that apply to any of the treatments described herein In any of the treatments of the invention described herein, sebetralstat is orally administered in a therapeutically effective amount.
  • the therapeutically effective amount can be between about 100 mg and about 1500 mg, about 300 mg and about 1800 mg, about 100 mg and about 1400 mg, about 200 mg and about 1200 mg, about 300 mg and about 1200 mg, about 600 mg and about 1200 mg, about 450 mg and about 900 mg, about 500 mg and about 1000 mg, about 450 mg and about 600 mg, about 500 mg and about 700 mg (more specifically, 600 mg), about 800 mg and about 1000 mg per day, about 900 mg and about 1400 mg (more specifically 1200 mg), or about 900 mg and about 1200 mg.
  • the therapeutically effective amount can be between about 250 mg and about 350 mg, between about 270 mg and about 330 mg, between about 275 mg and about 325 mg, between about 285 mg and about 315 mg, between about 290 mg and about 310 mg, or between about 295 mg and about 305 mg. Preferably the therapeutically effective amount is about 300 mg. As used herein, “about” means ⁇ 10%.
  • the sebetralstat is preferably in the free base form.
  • the patient can be aged 12 years and above. In particular, the patient can be aged between 12 and less than 18. Alternatively, the patient can be aged 18 years and above.
  • sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) is administered to reduce the time to beginning of symptom relief.
  • symptom relief in this context can mean that the attack is rated as “a little better” or higher for two consecutive time points when assessed according to the PGI-C scale.
  • PGI-C is a known index in the art that can be used to score the progression of an HAE attack and to report attacks as “much better”, “better”, “a little better”, “no change”, “a little worse”, “worse”, or “much worse”.
  • sebetralstat is administered to reduce the time to beginning of symptom relief to between about 0.7 and about 8 hours after the first dose of sebetralstat.
  • Symptom relief can start between about 1 and about 8 hours after the first dose.
  • Symptom relief can start between about 1 and about 6 hours after the first dose of sebetralstat.
  • Symptom relief can start between about 1 and about 4 hours after the first dose of sebetralstat.
  • Symptom relief can start between about 1 and about 2 hours after the first dose.
  • Symptom relief can start between about 1.5 and about 1.8 hours after the first dose.
  • Symptom relief can start at about 1.61 hours after the first dose of sebetralstat.
  • sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) is administered to reduce the time to a reduction in attack severity.
  • reduction in attack severity in this context can mean that the attack severity decreases from baseline by one or more levels on the PGI-S scale for two consecutive time points.
  • sebetralstat is administered to reduce the time to a reduction in attack severity to between about 1 and about 12 hours.
  • Reduction in attack severity can start between about 2 and about 11 hours.
  • Reduction in attack severity can start between about 3 and about 10 hours.
  • Reduction in attack severity can start between about 5 and about 10 hours.
  • Reduction in attack severity can start between about 9 and about 10 hours.
  • Reduction in attack severity can start between about 9 and about 9.5 hours. Reduction in attack severity can start at about 9.27 hours.
  • sebetralstat or a pharmaceutically acceptable salt and/or solvate thereof
  • the term “complete attack resolution” in this context can mean that the treatment improves the severity of the attack to “none” when assessed using the PGI-S scale.
  • sebetralstat is administered to achieve complete attack resolution within about 8 and about 24 hours. Complete attack resolution can be achieved within 24 hours. Complete attack resolution can be achieved within about 8 and about 20 hours. Complete attack resolution can be achieved within about 8 and about 17 hours.
  • sebetralstat or a pharmaceutically acceptable salt and/or solvate thereof
  • Sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) can administered as an oral dosage form comprising: (i) sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and (ii) at least one pharmaceutically acceptable excipient.
  • the oral dosage form can be a capsule.
  • the oral dosage form can be a tablet.
  • the tablet can be a film-coated tablet or an orodispersible tablet.
  • the oral dosage form can be a film-coated tablet comprising microcrystalline cellulose as a diluent, croscarmellose sodium as a disintegrant, polyvinyl pyrrolidone as a binder, and optionally magnesium stearate as a lubricant.
  • sebetralstat comprises: (i) at least about 40 wt% of the tablet (more specifically about 40 wt% to about 60 wt%), compared to the total mass of the tablet; (ii) about 25 wt% to about 60 wt% of the diluent (more specifically about 25 wt% to about 40 wt%, compared to the total mass of the tablet; (iii) about 1 wt% to about 15 wt% of the disintegrant (more specifically about 2 wt% to about 6 wt%), compared to the total mass of the tablet; (iv) about 1 wt% to about 20 wt% of the binder (more specifically about 2 wt% to about 5 wt%), compared to the total mass of the tablet; and when present, (v) about 0.1 to about 5 wt% lubricant (more specifically about 0.1 wt% to about 1.5 wt%), compared to the total mass of the tablet.
  • the dosage form can be a tablet containing about 250mg to about 350mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • the dosage form can be a tablet containing about 270mg to about 330mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • the dosage form can be a tablet containing about 275mg to about 325mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • the dosage form can be a tablet containing about 285mg to about 315mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • the dosage form can be a tablet containing about 290mg to about 310mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • the dosage form can be a tablet containing about 295mg to about 305mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • the dosage form can be a tablet containing about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • the orodispersible tablet can comprise between about 25 and about 50 wt% of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), one or more fillers (e.g. granulated mannitol and/or spray-dried mannitol) present at between about 30 and 80 wt% of the orodispersible tablet, one or more binders (e.g.
  • silicified microcrystalline cellulose present at between about 5 and about 30 wt% of the orodispersible tablet and one or more disintegrants (e.g. polyvinylpyrrolidone (crospovidone)) present at between 1 and about 10 wt% of the orodispersible tablet.
  • disintegrants e.g. polyvinylpyrrolidone (crospovidone)
  • sebetralstat or a pharmaceutically acceptable salt and/or solvate thereof
  • sebetralstat can be orally administered on-demand upon recognition of a symptom of an HAE attack.
  • sebetralstat or a pharmaceutically acceptable salt and/or solvate thereof
  • sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) can be orally administered on-demand for the treatment of patient-recognized attacks of HAE.
  • HAE patient-recognized hypertension
  • each HAE attack can be different in severity and in terms of the area affected, patients who suffer from HAE, medical professionals with knowledge of HAE, and carers of HAE patients are (and indeed the skilled person would be) astute in identifying symptoms of an HAE attack.
  • ⁇ symptoms include, but are not limited to: swelling of tissues such as in the hands, feet, limbs, face, intestinal tract, and/or airway; fatigue; headache; muscle aches; skin tingling; abdominal pain; nausea; vomiting; diarrhoea; difficulty swallowing; hoarseness; shortness of breath; and/or mood changes.
  • administration of sebetralstat can occur upon recognition of at least one of the above symptoms.
  • administered upon recognition of a symptom of a HAE attack means that administration occurs as quickly as feasibly possible after the symptom of an HAE attack is recognised.
  • sebetralstat or a pharmaceutically acceptable salt and/or solvate thereof
  • patients are expected to have sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) easily and readily available at all times (most likely in the form of a pharmaceutically acceptable composition) to ensure that treatment can occur upon recognition of a symptom of a HAE attack.
  • the treatment occurs on-demand.
  • sebetralstat can be administered within 1 hour of the symptom of an HAE attack being recognised, preferably within about 50 minutes, within about 40 minutes, within about 30 minutes, within about 20 minutes, within about 10 minutes, within about 6 minutes, or within about 5 minutes of the symptom of an acute HAE attack being recognised.
  • the symptom of an HAE attack is recognised in the prodromal phase, sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) can be administered in the prodromal phase of an HAE attack.
  • the symptom recognised can be a slight swelling, in particular, a slight swelling affecting the face and neck.
  • the symptom can be abdominal pain, in particular, abdominal pain is considered to be characteristic of a HAE attack.
  • the symptom can be a reddening of the skin such as erythema marginatum. In any of the above treatments, the symptom can be recognised by the patient.
  • the symptom can be recognised by a medical professional such as a medical professional with knowledge of HAE. In any of the above treatments, the symptom can be recognised by a carer of the patient.
  • the term “Compound” means sebetralstat.
  • Figure 1 X-ray powder diffraction pattern of the sebetralstat as generated in Example 1. Chart showing the distribution of attack severity (PGI-S) at baseline in patients using on-demand treatment ⁇ LTP. C heart showing the distribution of attack severity (PGI-S) at baseline in patients using sebetralstat 300mg, sebetralstat 600mg or placebo. 4 : Graph showing the time from onset of attack to the first IMP administration.
  • Figure 11 Graph showing the plasma concentration of sebetralstat when administered alone and with the strong CYP3A4 inducer phenytoin.
  • Figure 12 Graph showing the plasma concentration of sebetralstat when administered alone and with the strong CYP3A4 inducer phenytoin.
  • Figure 13 Graph showing the plasma concentration of sebetralstat when administered alone and with the moderate CYP3A4 inhibitor verapamil.
  • Figure 14 Graph showing the plasma concentration of sebetralstat when administered alone and with the moderate CYP3A4 inhibitor verapamil.
  • Figure 15 Graph showing the plasma concentration of sebetralstat when administered alone and with the moderate CYP3A4 inducer efavirenz.
  • Figure 16 Graph showing the plasma concentration of sebetralstat when administered alone and with the moderate CYP3A4 inducer efavirenz.
  • Figure 17 Graph showing proportion of attacks reaching primary or key secondary endpoints with 1 or 2 administrations of sebetralstat.
  • Figure 18 Graph showing hazard ratios of sebetralstat 600 mg compared with 300 mg for primary or key secondary endpoints by baseline attack severity.
  • Figure 19 Graph showing hazard ratios of sebetralstat 600 mg compared with 300 mg for primary or key secondary endpoints by treatment paradigm.
  • Figure 20 Graph showing number of sebetralstat-treated attacks in the open-label extension Phase 3 study of sebetralstat (Example 5).
  • Figure 21 Graph showing time from attack recognition to sebetralstat administration in the open-label extension Phase 3 study of sebetralstat (Example 5).
  • Figure 22 Graph showing time from onset of attack to treatment administration (Example 4).
  • Figure 23 Graph showing the probability for faster complete attack resolution (Example 4).
  • Figure 24 Graph showing time to complete attack resolution within 24 hours versus time to treatment for “mild”, or “moderate” or greater, attacks treated “earlier” and “later” (Example 4).
  • Figure 25 LOESS regression curve fitting time to complete attack resolution within 24 hours versus time to treatment (Example 4).
  • Figure 26 Graph showing baseline attack severity in attacks involving the larynx (Examples 4 and 5).
  • Figure 27 Graph showing time to treatment administration in all attacks treated in Example 4, all attacks treated in Example 5 and attacks involving the larynx treated in Examples 4 and 5.
  • Figure 28 Graph showing the proportion of attacks involving the larynx that reached primary and key secondary endpoints without an additional dose (Examples 4 and 5).
  • Figure 29 Graph showing sebetralstat effectiveness among participants receiving LTP in the open-label extension Phase 3 study of sebetralstat (Example 5).
  • Figure 30 Graph showing sebetralstat effectiveness among participants receiving berotralstat in the open-label extension Phase 3 study of sebetralstat (Example 5).
  • Figure 31 Graph showing effectiveness endpoints in attacks involving the larynx treated with sebetralstat in the open-label extension Phase 3 study of sebetralstat (Example 5).
  • Embodiments provided herein may be more fully understood by reference to the following examples. These examples are meant to be illustrative of treatments provided herein but are not in any way limiting. Indeed, the scope of the invention is defined by the claims. While examples of certain particular embodiments are provided herein, it will be apparent to those skilled in the art that various changes and modifications may be made. Such modifications are also intended to fall within the scope of the appended claims.
  • Example 1 Preparation of sebetralstat A.1-(4-Hydroxymethyl-benzyl)-1H-pyridin-2-one 4-(Chloromethyl)benzylalcohol (5.0 g, 31.93 mmol) was dissolved in acetone (150 mL).2-hydroxypyridine (3.64 g, 38.3 mmol) and potassium carbonate (13.24 g, 95.78 mmol) were added and the reaction mixture was stirred at 50 °C for 3 hrs after which time the solvent was removed in vacuo and the residue taken up in chloroform (100 mL).
  • reaction mixture was concentrated under reduced pressure and then triturated with ether, sonicated and then decanted to give a cream coloured solid (75 mg, 55% yield) identified as C-(3-fluoro-4-methoxy-pyridin-2-yl)-methylamine hydrochloride salt.
  • Tablet B was compressed at 6.9 to 7.7 kN compression force. Tablets C and D were compressed at approximately 17.5 kN compression force. The tablets were found to be robust. Tablets A, B, C and D were subsequently submitted for long-term stability testing. The production of tablets A and B per the method described above has been scaled to 180g with a roller compaction time of approximately 60 minutes. Tablets C and D were scaled to 9.66kg. Tablets C and D were film-coated with Opadry® II White (85F280012) (4% w/w).
  • Example 3 Preparation of an orodispersible tablet comprising sebetralstat ODTs of sebetralstat were prepared according to the following method. Method 1.
  • Table 1 Composition of sebetralstat 250 mg and 300 mg Orodispersible Tablets (ODTs) Components Function/ Blend Sebetralstat Sebetralstat Standard composition 250 mg ODT 300 mg ODT % w/w mg mg Sebetralstat Active 30.0 250.0 300 .0 Diluent Mannitol (Granulated) 26.85 223.7 268.5 (USP/NF, Ph Eur, JP) Mannitol (Mannogem Diluent 2 6.85 223.7 268.5 EZ) (USP/NF, Ph Eur, JP) Silicified Microcrystalline Diluent 1 0.00 83.3 100.0 Cellulose (USP/NF, Ph Eur, JP) Disintegrant Crospovidone 5.00 41.7 50.0 (USP/NF, Ph Eur, JP) Sweetener Sucralose 0.50 4.2 5.0 (USP/NF, Ph Eur) Flow Enhancer Silicon Dioxide 0.75 6.3 7.5 (USP/NF, Ph Eur, JP) Peppermint Natural Flavour
  • Example 4 Phase 3 study of sebetralstat A Randomized, Double-Blind, Placebo-Controlled, Phase 3, Three-way Crossover Trial to Evaluate the Efficacy and Safety of Two Dose Levels of sebetralstat (“the compound” or “study drug”), an Oral Plasma Kallikrein Inhibitor, for On-Demand Treatment of Angioedema Attacks in Adolescent and Adult Patients with Hereditary Angioedema Type I or II.
  • This trial was conducted at HAE treatment centres on an outpatient basis and will comprise in-clinic and televisits.
  • a televisit was conducted via a telephone call or a via an interactive audio/video system. If an in-clinic visit could not have been conducted (e.g. in the event of a pandemic or other reason that prevents the patient from attending the in-clinic visit) home health visits were used to perform these visits if permitted by the relevant regulatory authority, site’s Ethics Committee (EC)/ Institutional Review Board (IRB), local regulations, and the patient via informed consent.
  • the home visit was performed by an appropriately delegated home healthcare service provider. Information captured during a home health visit mirrored that captured in an in-clinic visit.
  • ⁇ Patient must have been able to complete at least the first 4 hours of eDiary assessments following the first administration of the study drug.
  • Post-attack televisit must have been completed for the previous eligible attack (applicable to eligible attacks 2 and 3 only). Eligible attacks should initially have been treated with a single administration of the study drug. Patients were encouraged to treat as soon as possible after the start of the attack. If needed (as determined by the patient), a second dose of the study drug was administered for each attack, as follows: Non-laryngeal attacks For each eligible HAE attack, a second dose of the study drug may have been taken: ⁇ after 3 hours if HAE attack symptoms were considered severe enough by the patient to require a second dose of the study drug.
  • conventional on-demand treatment may have been taken: ⁇ after 1 hour if HAE attack symptoms were considered severe enough by the patient to require treatment with conventional treatment. If symptoms progressed to airway involvement, patients may have treated with conventional on-demand treatment at any time. Laryngeal attacks After the first dose of the study drug, conventional on-demand treatment may have been taken at any time: ⁇ if HAE attack symptoms worsened or if HAE attack symptoms were considered severe enough by the patient to require immediate treatment. Attacks that did not meet eligibility may have been treated with conventional on-demand treatment per the patient’s usual treatment regimen.
  • Table 2 Frequency of Patient Assessment Time Period following Study Frequency of Patient Allowed Time Window for Drug Administration Assessment* Assessment 0 to 4 hours Every 0.5 hours ⁇ 0.25 hour 5 to 12 hours Every 1 hour ⁇ 0.5 hour 14 to 24 hours Every 2 hours ⁇ 1 hour 25 to 48 hours Every 12 hours ⁇ 3 hours * If a second dose of IMP or additional doses of conventional on-demand treatment were needed, patients completed diary assessments prior to taking each additional dose. After re-dosing, the planned post-dose diary assessments continued through 48 hours after first dose of the study drug.
  • Post-Attack Televisit A televisit (between the site staff and the patient) was completed following each administration of the study drug to ensure the safety and wellbeing of the patient, to confirm the study drug accountability, to review the patient diary (and retrain, if necessary), and to undergo an adverse event (AE) and concomitant medication review.
  • the televisit occurred by the next working day after the completion of the patient diary (visit window: +1 week).
  • Final Visit/Early Termination Once 3 HAE attacks were treated, or upon early termination, the patient returned to the clinic as soon as possible within 1 week for an in-clinic visit to undergo final safety checks including AE reporting, vital sign recording, and blood sampling for laboratory safety measurements. Whenever possible, this visit should have been completed prior to starting any new medication or treatment.
  • Investigational Medicinal Product Sebetralstat – 300 mg film-coated tablet. These contained the following excipients: microcrystalline cellulose, croscarmellose sodium, povidone, magnesium stearate; the aesthetic coating contains polyvinyl alcohol, titanium dioxide and polyethylene glycol 3350. Placebo for the compound tablet. These contained microcrystalline cellulose, croscarmellose sodium, povidone, magnesium stearate and are film-coated; the aesthetic coating contains polyvinyl alcohol, titanium dioxide and polyethylene glycol 3350. No study drug dose modifications were allowed in this study. Tablets must have been swallowed whole and were not to be crushed or modified in any way.
  • Eligible attacks should initially have been treated with a single administration of the study drug as soon as possible after the start of the attack. If needed (as determined by the patient), a second dose of the study drug may have been administered for each attack.
  • Number of Patients The trial population comprised 2 subsets: (1) patients who entered the trial taking only conventional on- demand treatment and (2) patients who entered the trial on a stable dose and regimen of long-term prophylactic treatment.
  • Population The trial population included male and female patients 12 years of age and older with a confirmed diagnosis of HAE type I or II.
  • the trial population included a subset of patients who enter the trial taking only conventional on demand treatment and a subset of patients who entered the trial on a stable dose and regimen of long-term prophylactic treatment.
  • Inclusion Criteria 1.
  • HAE type I or II Male or female patients 12 years of age and older. 2. Confirmed diagnosis of HAE type I or II at any time in the medical history: a. Documented clinical history consistent with HAE (sc or mucosal, nonpruritic swelling episodes without accompanying urticaria) and either: i. Diagnostic testing results obtained during the Screening Period that confirm HAE type I or II: C1-INH functional level ⁇ 40% of the normal level. Patients with functional C1-INH level 40-50% of the normal level may be enrolled if they also have a C4 level below the normal range. Patients may be retested during the Screening Period if results are incongruent with clinical history or believed by the Investigator to be confounded by recent prophylactic or therapeutic C1-INH use, or ii.
  • Acceptable methods of contraception include one or more of the following: i. Progestogen-only hormonal contraception associated with inhibition of ovulation: oral/injectable/implantable (hormonal contraception that contains estrogen including ethinylestradiol is excluded per Exclusion 4). ii. Intrauterine device. iii. Intrauterine hormone–releasing system. iv. Bilateral tubal occlusion. v. Vasectomized partner (provided that the partner is the sole heterosexual partner of the female patient of childbearing potential and that the vasectomized partner has received medical assessment of surgical success). vi.
  • Any concomitant diagnosis of another form of chronic angioedema such as acquired C1-inhibitor deficiency, HAE with normal C1-INH (previously known as HAE type III), idiopathic angioedema, or angioedema associated with urticaria.
  • HAE acquired C1-inhibitor deficiency
  • C1-INH normal C1-INH
  • idiopathic angioedema or angioedema associated with urticaria.
  • Angiotensin-converting enzyme (ACE) inhibitors after the Screening Visit or within 7 days prior to randomization. 4.
  • Any estrogen containing medications with systemic absorption (such as oral contraceptives including ethinylestradiol or hormonal replacement therapy) within 7 days prior to the Screening Visit. 5.
  • These medications include but are not limited to the following: Inhibitors: boceprevir, clarithromycin, cobicistat, dasabuvir, denoprevir, elvitegravir, idelalisib, indinavir, itraconazole, ketoconazole, lopinavir, nefazodone, nelfinavir ombitasvir, paritaprevir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, tipranavir, troleandomycin, and voriconazole.
  • Inhibitors boceprevir, clarithromycin, cobicistat, dasabuvir, denoprevir, elvitegravir, idelalisib, indinavir, itraconazole, ketoconazole, lopinavir, nefazodone, nelfinavir ombitasvir, paritaprevir, pos
  • Inducers apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John’s Wort. 6.
  • Inadequate organ function including but not limited to: a. Alanine aminotransferase (ALT) >2x upper limit of normal (ULN) b. Aspartate aminotransferase (AST) >2x ULN c. Bilirubin direct >1.25x ULN d. International normalized ratio (INR) >1.2 e. Clinically significant hepatic impairment defined as a Child-Pugh B or C. 7.
  • Safety Variables ⁇ Adverse events, including serious adverse events. ⁇ Laboratory test results. ⁇ 12-lead ECG. ⁇ Vital signs. ⁇ Physical examination findings. Criteria for Evaluation of Efficacy Primary Efficacy Endpoints: ⁇ PGI-C: Time to beginning of symptom relief defined as at least “a little better” (2 time points in a row) within 12 hours of the first study drug administration. Key Secondary Efficacy Endpoints: ⁇ PGI-S: Time to first incidence of decrease from baseline within 12 hours of the first study drug administration. ⁇ PGI-S: Time to HAE attack resolution defined as “none” within 24 hours of the first study drug administration.
  • ⁇ PGI-C Proportion of attacks with beginning of symptom relief defined as at least “a little better” (2 time points in a row) within 4 hours and within 12 hours of the first study drug administration.
  • ⁇ PGI-C Time to at least “better” within 12 hours of the first study drug administration.
  • ⁇ PGI-S Time to first incidence of decrease from baseline within 24 hours of the first study drug administration.
  • Composite VAS Time to at least a 50% decrease from baseline (3 time points in a row) within 12 hours and within 24 hours of the first study drug administration.
  • Safety Safety analyses were performed by treatment group using the safety set. Safety endpoints included AE, clinical laboratory assessments, vital signs, and ECG findings. Adverse events and serious adverse events (SAEs) recorded during the trial were summarized by system organ class, preferred term, and treatment. Adverse events and medical history were coded using the most current version of MedDRA. Frequencies and percentages of patients with treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs causing premature discontinuation were provided by treatment group. Patient listings of all AEs were provided as well as listings of deaths, SAEs, and AEs leading to discontinuation.
  • SAEs serious adverse events
  • Figure 3 shows the distribution of attack severity (PGI-S) at baseline in patients using sebetralstat 300mg, sebetralstat 600mg or placebo.
  • Figures 2 and 3 demonstrate that patients receiving prophylactic treatment still suffer from HAE attacks and, notably, still suffer from severe and very severe HAE attacks.
  • Figure 17 is a graph showing the proportion of attacks reaching beginning of symptom relief (PGI-C) with 1 or 2 administrations of sebetralstat.
  • Figure 17 is a graph showing proportion of attacks reaching reduction in attack severity (PGI-S) with 1 or 2 administrations of sebetralstat.
  • Table 16 Subgroups by Population Characteristics (time to complete attack resolution) Time to complete attack Sebetralstat 300 mg Sebetralstat 600 mg Placebo resolution a C ategory n Median n Median n Median (95% CI) (95% CI) Current HAE treatment O n-demand with LTP 19 17.05 (10.55, 21 19.24 (5.03, NE) 18 16.49 (7.46, NE) NE) O n-demand 68 NE (22.9, NE) 72 NE (10.52, NE) 66 NE (NE, NE) Age A dolescent 10 NE (3.28, NE) 11 NE (0.33, NE) 9 NE (1.55, NE) Adult 77 NE (16.60, NE) 82 21.02 (10.59, NE) 75 NE (NE, NE) Geography U S 27 NE (10.55, NE) 28 21.46 (13.02, NE) 23 NE (14.38, NE) Europe 44
  • ⁇ “Later” treatment was defined as treatment in the fourth quartile of time to treatment, i.e., those attacks in which sebetralstat was administered on or after 140 minutes from onset of attack.
  • the median time from attack onset to treatment administration was 41 minutes (IQR, 6-140).
  • Figure 22 shows that 79 attacks were treated within 6 minutes.
  • Figure 8 is a graph showing the cumulative % of patients with a 50% reduction in composite VAS score within 24 hours of IMP administration. Figure 8 shows that the time to 50% reduction in composite VAS score was faster for both 300mg and 600mg sebetralstat compared to placebo.
  • ⁇ Serious TEAE was defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event by medical and scientific judgement.
  • the severe TEAE and serious TEAE listed are the same event; lumbar disc herniation that required hospitalization and was deemed severe by the investigator.
  • ⁇ Severe TEAE was defined as a qualitative assessment of an AE of grade 3 severity by the investigator or as reported by the patient.
  • On-Demand Treatment of HAE Attacks Patients take a single dose of 600 mg sebetralstat (i.e. 2 x 300 mg tablets) to treat each HAE attack. Patients are permitted to take a second dose of 600 mg sebetralstat separated by at least 3 hours following the first dose if attack symptoms persist without improvement.
  • Conventional on-demand treatment may be used upon patients’ discretion and in consultation with their physician.
  • Laryngeal attacks may be treated with the IMP in this trial; all patients are instructed to treat immediately with conventional on-demand treatment if laryngeal attack symptoms worsen after initial treatment with IMP.
  • Short-term Prophylactic Therapy Patients can use sebetralstat as short-term prophylactic therapy prior to undergoing surgical, dental, or medical procedures.
  • sebetralstat for short-term prophylactic therapy is made on a case-by-case basis, after consultation with the Investigator and the patient, and based on whether treatment with sebetralstat for short-term prophylactic therapy is medically appropriate for the patient.
  • Patients are permitted to take up to a maximum of 3 doses of sebetralstat in a 24-hour period as short- term prophylaxis, with each dose approximately 6 hours apart, starting approximately 1 hour prior to the start of the procedure.
  • sebetralstat cannot be used for short-term prophylaxis if the patient had an attack within the last 48 hours or has not completed their last eDiary assessment for that attack.
  • Short-term prophylactic therapy must stop if an HAE attack occurs that is treated with IMP or conventional on-demand treatment.
  • Efficacy endpoints are as follows: 1. PGI-C: HAE attacks with symptom relief defined as at least “a little better” (2 time points in a row) within 12 hours of initial dose of IMP administration. 2. PGI-S: HAE attacks with any decrease from baseline within 12 hours of initial dose of IMP administration. 3. PGI-S: HAE attacks that resolved, defined as “none” within 24 hours of initial dose of IMP administration. 4. AE-QoL (exploratory): AE-QoL change over time.
  • Endpoints 1 through 3 are summarized by proportions (number of HAE attacks that meet the endpoint [endpoints 1 through 3] that occur in patients from the FAS divided by the total number of HAE attacks across all patients in the FAS).
  • Endpoint AE-QoL (4) are summarized as a continuous variable over time. For each patient, the time observed in the trial, the number of HAE attacks experienced, the number of IMP-treated attacks (single-dose and two doses) and the number of attacks treated with conventional on- demand treatment are described, alongside the characteristics of the attacks (location, severity). This is summarized for all patients in the FAS.
  • Sebetralstat exposure Participants treated a median of five attacks with sebetralstat (IQR, 2 to 8; range, 1 to 37; Figure 20). Twenty participants treated at least nine attacks.
  • Figure 20 is a graph showing the number of sebetralstat-treated attacks in the open-label extension Phase 3 study of sebetralstat. The median time from attack recognition to treatment was 9 minutes (IQR, 1 to 69; Figure 21). Fourteen laryngeal attacks (2.2%) were treated with sebetralstat, with a median time from onset of attack to first administration of 8.0 minutes (IQR, 1.0 to 27.0).
  • Figure 21 is a graph showing the time from attack recognition to sebetralstat administration in the open- label extension Phase 3 study of sebetralstat.
  • aSerious TEAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpa ⁇ ent hospitaliza ⁇ on or prolonga ⁇ on of exis ⁇ ng hospitaliza ⁇ on, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event by medical and scien ⁇ fic judgment.
  • b Severe (grade 3 or 4) TEAEs were evaluated by inves ⁇ gators according to the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preven ⁇ ve Vaccine Clinical Trials (US Department of Health and Human Services.
  • a Includes participants who experienced an attack involving the larynx treated with sebetralstat 600 mg in Example 4 or Example 5.
  • Figure 26 shows that most (68.9%) attacks involving the larynx had a PGI-S rating of moderate (43.8%), severe (18.8%), or very severe (6.3%) at baseline.
  • Figure 27 shows that the median time to oral sebetralstat administration to treat an attack involving the larynx was 8 minutes (IQR: 1-30).
  • Example 4 a second administration of study treatment was not permitted for attacks involving the larynx. However, a second administration of sebetralstat 600 mg was permitted for attacks involving the larynx in Example 5. b Attacks involving the larynx could be treated with conventional on-demand treatment at any time and all participants were instructed to treat immediately with conventional on-demand treatment if laryngeal attack symptoms worsened following initial study treatment. c Includes conventional on-demand treatment administered within 12 hours of first administration sebetralstat 600 mg in Example 4 or Example 5. d One participant reported administering conventional on-demand treatment one minute after sebetralstat administration (the endpoint was censored at 12 hours).
  • Subgroup analysis of treatment of HAE attacks in patients receiving LTP 35 participants receiving LTP experienced 504 attacks of which 382 (76%) were treated with sebetralstat. Of these, 16 participants receiving berotralstat treated 178 attacks, 13 participants receiving lanadelumab treated 80 attacks, and 6 participants receiving C1INH replacement treated 124 attacks. Participants receiving LTP experienced a mean (SD) of 1.71 (1.48) attacks per month (berotralstat: 1.8 (1.2); lanadelumab: 1.2 (0.8); C1-INH: 2.5 (2.1)).
  • SD mean
  • the median time to treatment was 6 minutes (IQR, 1-40) (berotralstat: 20.0 minutes (1.0-67.0); lanadelumab: 11.0 minutes (1.0-50.0); C1-INH: 1.0 minutes (0.0-7.0)).
  • SD the mean
  • PKI-S Patient Global Impression of Severity
  • the median (IQR) attack frequency was 1.0 (0.6 to 2.7) attacks per month in participants receiving LTP, 1.2 (0.6 to 3.4) attacks per month in participants receiving berotralstat, 0.8 (0.7 to 1.0) attacks per month in participants receiving lanadelumab, and 2.1 (1.2 to 2.7) attacks per month in participants receiving C1INH replacement.
  • Figure 29 shows that sebetralstat was effective in treating HAE attacks and provided fast symptom relief in participants having attacks whilst on LTP.
  • the median time to beginning of symptom relief was 1.3 hours (0.8-3.8) for participants receiving LTP, 1.3 hours (0.4-2.5) for participants receiving berotralstat, 1.3 hours (1.2-1.6) for participants receiving lanadelumab, and 1.8 hours (1.3->12) for participants receiving C1-INH.
  • the median (IQR) attack frequency was 1.2 (0.6 to 3.4) attacks per month in participants who were receiving berotralstat.
  • the median time to treatment was 20 minutes (IQR, 1-67).
  • Table 5.13: Patient Demographics Patients receiving berotralstat (N 16) Age, median (IQR), years 38.5 years (21.0 to 48.0) Age group, n (%) ⁇ 12 to ⁇ 18 years 4 (25.0) ⁇ 18 years 12 (75.0) S ex, female, n (%) 13 (81.3) Race, n (%) White 10 (62.5) Asian 4 (25.0) Other or multiple 1 (6.3) Not reported 1 (6.3) BMI, median (IQR), kg/m 2 27.1 (21.6 to 33.8) HAE-C1INH type, n (%) Type 1 15 (93.8) Type 2 1 (6.3) BMI, body mass index; HAE-C1INH, hereditary angioedema due to deficiency or dysfunction of C1 inhibitor; IQR, interquartile range; LTP, long- term prophylaxis
  • the method according to embodiment 164, wherein the prophylactic treatment is berotralstat. 167.
  • the method according to any of embodiments 124 to 167, wherein the HAE attack is selected from a laryngeal attack, an attack of the neck and above, an attack of the neck and a bove that is not a laryngeal attack, an abdominal attack, and a subcutaneous attack. 169.
  • the method according to embodiment 168, wherein the HAE attack is a laryngeal attack. 170.
  • the method according to embodiment 168, wherein the HAE attack is an attack of the neck and above. 171.
  • the patient is administered a third dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • the third dose is administered between about 2 hours and about 6 hours after the second dose.
  • the third dose is administered about 3 hours after the second dose. 201.
  • 202. The method according to any of embodiments 198 to 200, wherein the patient is administered a fourth dose of about 300mg of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • 203. The method according to embodiment 202, wherein the fourth dose is administered between about 2 hours and about 6 hours after the third dose.
  • 204. The method according to embodiment 203, wherein the fourth dose is administered about 3 hours after the third dose.
  • 205. The method according to any of embodiments 202 to 204, wherein the attack is resolved without administering any further dose to the patient. 206.
  • each dose is administered as one tablet.
  • 207 The method according to any of embodiments 186 to 206, wherein sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) is administered as part of a pharmaceutical composition.
  • 208 The method according to any of embodiments 186 to 207, wherein sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) is administered as an oral dosage form comprising: (i) sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof), and (ii) at least one pharmaceutically acceptable excipient.
  • the oral dosage form is a tablet.
  • the method according to embodiment 209, wherein the tablet is a film-coated tablet. 211.
  • the method according to embodiment 209, wherein the tablet is an orodispersible tablet.
  • 212. The method according to any of embodiments 186 to 211, wherein the attack is resolved without administering a second treatment to the patient. 213.
  • the method according to any of embodiments 186 to 212, wherein the patient is aged 12 years and above. 214.
  • the method according to embodiment 213, wherein the patient is aged between 12 and less than 18. 215.
  • the method according to any of embodiments 186 to 215, wherein the patient is also being treated with a prophylactic treatment of HAE. 217.
  • the method according to 225, wherein the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. 227.
  • C1INH replacement therapy such as Cinryze®, Ruconest®, Berinert®, or Haegarda®
  • donidalorsen and deucrictibant. 227.
  • the method according to embodiment 225, wherein the prophylactic treatment is Cinryze®, Haegarda®, or Berinert®. 228.
  • the method according to 225, wherein the prophylactic treatment is selected from lanadelumab and berotralstat. 229.
  • the method according to embodiment 228, wherein the prophylactic treatment is lanadelumab. 230.
  • the method according to embodiment 228, wherein the prophylactic treatment is berotralstat. 231.
  • 232. The method according to any of embodiments 186 to 231, wherein the HAE attack is characterised as “mild” or above according to the PGI-S scale.
  • 233. The method according to embodiment 232, wherein the HAE attack is characterised as “mild”, according to the PGI-S scale. 234.
  • the method according to embodiment 232, wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale. 235.
  • the method according to embodiment 234, wherein the HAE attack is characterised as “moderate”, according to the PGI-S scale. 236.
  • the method according to embodiment 234, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale. 237.
  • the method according to embodiment 236, wherein the HAE attack is characterised as “severe”, according to the PGI-S scale. 238.
  • the method according to embodiment 236, wherein the HAE attack is characterised as “very severe”, according to the PGI-S scale. 239.
  • the method according to any of embodiments 186 to 238, wherein the attack of the neck and above is not a laryngeal attack. 240.
  • a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale. 2 50.
  • the method according to embodiment 249, wherein the HAE attack is characterised as “very severe” according to the PGI-S scale. 2 52.
  • the HAE attack is selected from a laryngeal attack, an attack of the neck and above, an abdominal attack, and a subcutaneous attack. 2 53.
  • the method according to embodiment 252, wherein the HAE attack is an attack of the neck and above.
  • the method according to embodiment 252, wherein the HAE attack is an abdominal attack.
  • the method according to embodiment 252, wherein the HAE attack is a subcutaneous attack. 257.
  • the method according to embodiment 254, wherein the attack of the neck and above is not a laryngeal attack. 258.
  • a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: administering a plasma kallikrein inhibitor to a patient in need thereof on-demand, wherein the patient is also being treated with a prophylactic treatment of HAE, and wherein the H AE attack is an attack of the neck and above but is not a laryngeal attack.
  • HAE hereditary angioedema
  • the method according to embodiment 259, wherein the HAE attack is characterised as “moderate” or above according to the PGI-S scale. 262.
  • the method according to embodiment 261, wherein the HAE attack is characterised as “moderate”, according to the PGI-S scale. 263.
  • the method according to embodiment 261, wherein the HAE attack is characterised as “severe” or above according to the PGI-S scale. 264.
  • the method according to embodiment 263, wherein the HAE attack is characterised as “severe”, according to the PGI-S scale. 265.
  • the method according to embodiment 263, wherein the HAE attack is characterised as “very severe”, according to the PGI-S scale. 266.
  • the prophylactic treatment is an attenuated androgen. 271.
  • the method according to any of embodiments 249 to 268, wherein the prophylactic treatment is tranexamic acid. 273.
  • the method according to any of embodiments 249 to 268, wherein the prophylactic treatment is non-androgen therapy. 274.
  • the method according to any of embodiments 249 to 268, wherein the prophylactic treatment is a C1 inhibitor.
  • the method according to any of embodiments 249 to 268, wherein the prophylactic treatment is a Factor XIIa (FXIIa) inhibitor. 276.
  • FXIIa Factor XIIa
  • the prophylactic treatment is a plasma kallikrein inhibitor. 277.
  • the prophylactic treatment is selected from lanadelumab, garadacimab, berotralstat, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. 278.
  • the method according to embodiment 277, wherein the prophylactic treatment is selected from garadacimab, STAR 0215, C1INH replacement therapy (such as Cinryze®, Ruconest®, Berinert®, or Haegarda®), donidalorsen, and deucrictibant. 279.
  • C1INH replacement therapy such as Cinryze®, Ruconest®, Berinert®, or Haegarda®
  • donidalorsen and deucrictibant. 279.
  • the method according to embodiment 277, wherein the prophylactic treatment is Cinryze®, Haegarda®, or Berinert®.
  • the method according to embodiment 277, wherein the prophylactic treatment is selected from lanadelumab and berotralstat. 281.
  • the method according to embodiment 280, wherein the prophylactic treatment is lanadelumab. 282.
  • the method according to embodiment 280, wherein the prophylactic treatment is berotralstat. 283.
  • the method according to any of embodiments 249 to 282, wherein the plasma kallikrein inhibitor that is administered to the patient on-demand is sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • sebetralstat or a pharmaceutically acceptable salt and/or solvate thereof
  • symptom relief means that the attack is rated as “a little better” or higher for two consecutive time points when assessed according to the PGI-C scale. 2 86.
  • a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient has taken, or will take, a concomitant dose of a strong or moderate CYP3A4 inhibitor and wherein the method comprises reducing the normal dose of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof). 295.
  • the method according to embodiment 294, wherein the method for treating is as described in any of the preceding embodiments. 296.
  • the strong CYP3A4 inhibitor is selected from itraconazole, ketoconazole, ritonavir, elvitegravir and ritonavir, indinavir and ritonavir, lopinavir and ritonavir, clarithromycin, ceritinib, cobicistat, idelalisib, nefazodone, nelfinavir, paritaprevir and ritonavir and (ombitasvir and/or dasabuvir), posaconazole, saquinavir and ritonavir, telithromycin, tipranavir and ritonavir, voriconazole, darunavir , telaprevir, stiripentol, curcumin, troleandomycin, atazanavir, naloxone, nilotinib, delavirdine, loperamide, ribociclib
  • the moderate CYP3A4 inhibitor is selected from verapamil, aprepitant, ciprofloxacin, conivaptan, crizotinib, diltiazem, dronedarone, erythromycin, fluconazole, grapefruit juice, imatinib, isavuconazole, isavuconazonium, luliconazole, netupitant, miconazole, nicardipine, isoniazid, danazol, lovastatin, ziprasidone, desvenlafaxine, indalpine, zimelidine, milnacipran, fusidic acid, barnidipine, benidipine, isradipine, haloperidol, linagliptin, fosnetupitant, simeprevir, nilvadipine, primaquine, clozapine, tioconazole, venetoclax, seproxetine, flu
  • a method for treating an attack of hereditary angioedema (HAE) on-demand comprising: orally administering sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) to a patient in need thereof on-demand, wherein the patient has taken, or will take, a concomitant dose of a strong or moderate CYP3A4 inducer and wherein the method comprises increasing the normal dose of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • HAE hereditary angioedema
  • the method for treating is as described in any of the preceding embodiments. 310.
  • the method according to embodiment 308 or 309, wherein the method comprises increasing the normal dose of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) so as to compensate for the effect experienced during co-administration.
  • the method according to embodiment 310, wherein the effect experienced during co- administration is a decreased therapeutic effect of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof).
  • the method according to any of embodiments 308 to 311, wherein the dose of sebetralstat (or a pharmaceutically acceptable salt and/or solvate thereof) is increased by about 10% to about 60% of the normal dose for the patient. 313.

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Abstract

La présente invention concerne des traitements de l'angioedème héréditaire (HAE). En particulier, la présente invention concerne des traitements à la demande de l'angioedème héréditaire (HAE) par administration par voie orale de l'inhibiteur de la kallicréine plasmatique sébetralstat à un patient en ayant besoin à la demande.
PCT/GB2025/050237 2024-02-13 2025-02-07 Sebetralstat à administrer par voie orale pour le traitement d'une attaque d'angioedème héréditaire Pending WO2025172692A1 (fr)

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