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WO2025010085A1 - Thérapie à base d'anticorps anti-ige pour allergies alimentaires multiples - Google Patents

Thérapie à base d'anticorps anti-ige pour allergies alimentaires multiples Download PDF

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WO2025010085A1
WO2025010085A1 PCT/US2023/070637 US2023070637W WO2025010085A1 WO 2025010085 A1 WO2025010085 A1 WO 2025010085A1 US 2023070637 W US2023070637 W US 2023070637W WO 2025010085 A1 WO2025010085 A1 WO 2025010085A1
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body weight
total serum
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Ryan Patrick OWEN
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Genentech Inc
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Genentech Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/42—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins
    • C07K16/4283—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an allotypic or isotypic determinant on Ig
    • C07K16/4291—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an allotypic or isotypic determinant on Ig against IgE
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • 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
    • A61K9/08—Solutions
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans

Definitions

  • the present disclosure provides methods and kits for treating or preventing an allergic reaction to a food allergen consumed by a human subject with one or more food allergies.
  • the present disclosure provides prophylactic therapies comprising administration of an anti-IgE antibody at a specific dose to a human subject who is allergic to one or more food allergens.
  • prophylactic therapies comprising administration of an anti-IgE antibody at a specific dose to a human subject who is allergic to one or more food allergens.
  • BACKGROUND OF THE INVENTION [0004] Food allergy affects approximately 15 million patients in the U.S., including six million children. It causes substantial morbidity and mortality, and it is the most common cause of anaphylaxis in pediatric patients seen in emergency departments across the U.S. (Gupta et al., JAMA Pediatr, 167:1026-1031, 2013).
  • FIG. 1 is a flow chart of a study design for testing omalizumab in food allergy, including Screening, Stage 1, and Stage 1 open label extension phases of the study as described in Example 1 herein.
  • FIG. 2 is a dosing table for omalizumab based on body weight and a baseline total serum IgE of the patient. The dosing frequency is indicated by each cell: gray shading is once every 4 weeks; no shading is once every 2 weeks; and black shading is do not dose.
  • the present disclosure provides methods and kits for treating a human subject having or diagnosed with a food allergy to one or more food allergens.
  • the subject is practicing food avoidance.
  • the subject has or may accidentally consume a food containing the one or more food allergens.
  • the subject is at risk of being exposed to the one or more food allergens.
  • the treating prevents or reduces an allergic reaction in the subject following consumption of food containing the one or more food allergens.
  • the present disclosure provides prophylactic therapies comprising administration of an anti-IgE antibody at a specific dose and frequency to a human subject.
  • the human subject is allergic to one or more food allergens. In some embodiments, the human subject is allergic to peanuts and one, two or more additional food allergens. In some embodiments, the subject is equal to or greater than 6 years of age.
  • the anti-IgE antibody is omalizumab.
  • omalizumab marketed by Genentech USA, Inc., South San Francisco, CA, and Novartis Pharmaceuticals Corporation, East Hanover, NJ
  • XOLAIR® omalizumab marketed by Genentech USA, Inc., South San Francisco, CA, and Novartis Pharmaceuticals Corporation, East Hanover, NJ
  • OIT oral immunotherapy
  • a food allergy includes one or more food allergies.
  • the phrase “comprising” as used herein is open-ended, indicating that such embodiments may include additional elements.
  • the phrase “consisting of” is closed, indicating that such embodiments do not include additional elements (except for trace impurities).
  • the phrase “consisting essentially of” is partially closed, indicating that such embodiments may further comprise elements that do not materially change the basic characteristics of such embodiments.
  • the term “about” as used herein in reference to a value encompasses from 95% to 105% of that value.
  • a dose of about 150 g/L omalizumab refers to a dose of from 142.5 g/L omalizumab to 157.5 g/L omalizumab and includes 150 g/L omalizumab.
  • a “food allergen” is a food, typically a food containing protein(s), that can trigger an allergic reaction upon consumption of the food or at times just exposure to minute amounts of the food by a sensitive individual.
  • total serum IgE or “serum total IgE” refers to a total amount of IgE present in a serum sample. Serum total IgE can be measured, for example, by an ELISA (enzyme-linked immunosorbent assay).
  • Total IgE includes free, 3 sf-5598576 Attorney Docket No.: 146392067340 unbound IgE and IgE complexed with a binding partner.
  • Free IgE refers to IgE not bound to a binding partner.
  • allergen-specific IgE refers to IgE that is specific to a particular antigen, resulting from an initial exposure to allergen in a process known as allergy sensitization.
  • a “baseline” level such as baseline level for body weight, serum total IgE, and allergen-specific IgE in a human refers to the body weight of the subject or the level (concentration) of serum total IgE before the first dose of an anti-IgE antibody. These may be referred to herein as “pretreatment” values.
  • treatment can include “prevention” or “reduction.”
  • prevention includes providing prophylaxis with respect to occurrence or recurrence of an IgE-mediated disorder (e.g., allergic reaction to a food allergen) in an individual (e.g., human subject).
  • reduction includes lessening of the severity of symptoms as described in Table 1-1.
  • an “effective amount” or “therapeutically effective amount” of an agent, or e.g., a pharmaceutical formulation comprising the agent refers to an amount effective, at dosages and for periods of time or at dosing frequency necessary, to achieve the desired therapeutic or prophylactic result, such as a measurable improvement in the state, e.g., reduction in symptoms such as those commonly experienced by a subject suffering from a food allergy.
  • a therapeutically effective amount may reduce or prevent symptoms of a disorder.
  • the terms, “prophylaxis,” “prophylactic,” “prophylactically,” and the like refer to treatment to protect a subject from the occurrence or recurrence of an IgE-mediated disorder (e.g., allergic reaction to a food allergen) resulting from intentional or accidental exposure to or consumption of a food allergen.
  • an IgE-mediated disorder e.g., allergic reaction to a food allergen
  • the terms “determine” and “determining” as used herein refer to ascertaining a particular fact or piece of information about a patient, e.g., using an ELISA to determine the serum total IgE of a subject.
  • Determining includes, e.g., querying a subject or referring to a document which contains the fact or piece of information about a subject, such as the body weight and/or serum total IgE of a patient. 4 sf-5598576 Attorney Docket No.: 146392067340 [0022]
  • the terms “allergic reaction” and “allergic response” as used herein refer to the experience by a human subject who is exposed to and/or consumes a food containing a food allergen to which the human subject is allergic, wherein the human subject experiences or exhibits dose-limiting symptoms which are mild, moderate, and/or severe symptoms which are characteristic of an allergic reaction to a food allergy.
  • dose-limiting symptoms or “food allergy reaction symptoms” as used herein refers to symptoms experienced by a subject having a food allergy wherein when the subject experiences a food allergic response or allergic reaction to one or more food allergens, the subject experiences one or more dose-limiting symptoms involving the skin, respiratory tract, and/or gastrointestinal tract, as well as neurological and/or circulatory symptoms in the case of severe allergic reactions.
  • dose-limiting symptoms or “food allergy reaction symptoms” as used herein refers to symptoms experienced by a subject having a food allergy wherein when the subject experiences a food allergic response or allergic reaction to one or more food allergens, the subject experiences one or more dose-limiting symptoms involving the skin, respiratory tract, and/or gastrointestinal tract, as well as neurological and/or circulatory symptoms in the case of severe allergic reactions.
  • oral immunotherapy refers to feeding a food allergen to an allergic individual in an increasing amount in order to desensitize the individual to the food.
  • oral immunotherapy to peanut involves feeding peanut to an allergic individual at increasing amounts over a period of time to increase the threshold of peanut (amount in milligrams) that would trigger an allergic reaction upon consumption by the individual.
  • the term “food avoidance” refers to the active effort or intent by a subject to not ingest or consume any foods that do or may contain a food allergen to which the subject knows or suspects he is allergic. A subject who practices food avoidance may accidentally be exposed to or unintentionally ingest or consume a food that contains the allergen(s) to which that subject is allergic. I.
  • Anti-IgE Antibodies 6 sf-5598576 Attorney Docket No.: 146392067340 [0027]
  • the methods, uses, medicaments and kits of the present disclosure for treating or preventing an allergic reaction to a food allergen consumed by a human subject with a food allergy to one or more food allergens involve administration of an anti-IgE antibody at a specific dose and frequency to the subject.
  • the subject is allergic to peanuts.
  • the subject is allergic to peanuts and one, two, or more additional food allergens.
  • the anti-IgE antibodies of the methods and kits of the present disclosure block binding of human IgE to the high affinity human IgE Receptor (Fc ⁇ RI).
  • the anti-IgE antibody is omalizumab or monoclonal antibody comprising CDR-H1 (GYSITSGY, set forth as SEQ ID NO:5), CDR-H2 (TYDGS, set forth as SEQ ID NO:6), CDR-H3 (GSHYFGHWHFAV, set forth as SEQ ID NO:7), CDR-L1 (RASQSVDYDGDSYMN, set forth as SEQ ID NO:8), CDR-L2 (AASYLES, set forth as SEQ ID NO:9) and CDR-L3 (QQSHEDPYT, set forth as SEQ ID NO:10).
  • the anti-IgE antibody is omalizumab.
  • the anti- IgE antibody is a biosimilar of omalizumab.
  • Omalizumab (CAS Registry No. 242138-07-4) is a recombinant DNA- derived, humanized IgG1 monoclonal antibody with a molecular weight of approximately 149 kDa that selectively binds to human IgE.
  • the amino acid sequences of the heavy chain variable region (VH) and the light chain variable region (VL) of omalizumab are shown as the E25 sequences in Figure 2 of U.S. Patent No. 6,172,213, and are set forth herein as SEQ ID NO:1 and SEQ ID NO:2, respectively.
  • Omalizumab is designed to treat IgE-mediated disease by reducing the concentration of free IgE in blood and in tissue.
  • Omalizumab selectively binds to human IgE at the same site of the IgE molecule that binds to the high affinity IgE Receptor (Fc ⁇ RI), thereby reducing IgE bound to the surface of basophils, mast cells, and dendritic cells and reducing basophil, mast cell, and dendritic cell-triggered Type 2 inflammation.
  • XOLAIR® (omalizumab marketed by Genentech USA, Inc., South San Francisco, CA, and Novartis Pharmaceuticals Corporation, East Hanover, NJ) is approved by the European Commission and the USFDA for treatment of other indications in older children and adults.
  • omalizumab is approved for patients with moderate-to- 7 sf-5598576 Attorney Docket No.: 146392067340 severe persistent asthma, nasal polyps, and chronic spontaneous urticaria. However, omalizumab is not currently approved for treating food allergy in any patient population.
  • Omalizumab is commercially available as a lyophilized powder contained in a single-use vial that is reconstituted with sterile water for injection. Omalizumab is administered by subcutaneous (SC) injection. It is also commercially available as a prefilled syringe administered by SC injection. II.
  • an anti- IgE antibody such as omalizumab
  • omalizumab is administered to a human subject with a food allergy to one or more food allergens in an amount and/or dosing frequency to reduce or prevent an allergic reaction to consumption of a food containing the food allergen(s) by the human subject.
  • the methods, uses, medicaments and kits of the present disclosure are contemplated to be especially valuable for patients with a high a total serum IgE level (e.g., from about 700 IU/ml to about 2000 IU/ml).
  • omalizumab is to be used in conjunction with food allergen avoidance. In some embodiments, omalizumab is not indicated for the emergency treatment of allergic reactions. In some embodiments, omalizumab is not indicated for the emergency treatment of anaphylaxis.
  • A. Methods of Use [0033] The present disclosure relates to methods of treating a human subject diagnosed with a food allergy to one or more food allergens with a therapeutically effective amount of omalizumab. In some embodiments, the methods of treating include preventing or reducing an allergic reaction to the one or more food allergens following exposure to or consumption by the subject.
  • the method of treating reduces the risk of an allergic reaction by the subject to exposure to or consumption of a food allergen to which the subject is allergic. In some embodiments, the method of treating reduces the severity of an allergic reaction to exposure to or consumption of a food allergen to which the subject is allergic. In some embodiments, the method of treating protects a human subject from an allergic reaction to a food allergen to which the subject is allergic. [0034] In some embodiments, the method of treating comprises: administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of omalizumab. In some embodiments, the pharmaceutical composition of omalizumab is administered to the subject by subcutaneous injection.
  • the 8 sf-5598576 Attorney Docket No.: 146392067340 therapeutically effective amount of omalizumab is administered to the subject prior to exposure to or consumption of the one or more food allergens. In some embodiments, the therapeutically effective amount of omalizumab is administered to the subject prophylactically prior to consumption of the one or more food allergens. In some embodiments, the method does not comprise concurrent oral immunotherapy with the food allergen. In some embodiments, the subject is practicing food avoidance. [0035] In some embodiments of the methods described herein, the methods further comprise determining the body weight and the total serum IgE level of the subject prior to administration of the first dose of omalizumab.
  • a subject may gain or lose body weight during the course of treating the subject with omalizumab for a food allergy. Accordingly, the dose amount and/or frequency may change during the course of treatment.
  • the dose of omalizumab may be changed relative to the first dose and in accordance with the dosing table of FIG. 2, wherein a subsequent dose (any dose which is administered after the first dose) is selected based on the body weight of the subject which is determined after the first dose but prior to the subsequent dose.
  • the selection of the dose may not include consideration of a change in serum total IgE levels from the serum total IgE levels determined no more than 4 weeks, 2 weeks, 1 week, 5 days, 4 days, 3 days, 2 days, or 24 hours prior to the first dose (e.g., the baseline serum total IgE concentration).
  • the methods of treatment further comprise determining the body weight of the subject prior to administration of a subsequent dose of omalizumab to obtain a current body weight of the subject, wherein the subsequent dose administered to the subject is based on the current body weight of the subject at a time after the first dose and prior to the subsequent dose, and wherein the dose is based on the body weight of the subject prior to the subsequent dose and on the serum total IgE levels determined prior to the first dose of omalizumab and according to the dosing table shown in FIG. 2.
  • the subsequent dose is administered within 1 day, 1 week, 2 weeks, or 4 weeks of the determination of the current body weight of the subject.
  • the methods further comprise determining the age of the subject prior to administration of the first dose of omalizumab.
  • the present disclosure provides further relates to methods of preventing an allergic reaction to consumption of a food allergen in a human with or more food allergies, the method comprising: administering by subcutaneous injection to the subject a pharmaceutical composition comprising omalizumab at a dose of 75 mg to 600 mg omalizumab and a dosing interval of every 2 or 4 weeks when body weight of the subject is 9 sf-5598576 Attorney Docket No.: 146392067340 greater than 25 kg and less than or equal to 150 kg, baseline total serum IgE level of the subject is equal to or greater than about 30 IU/ml and less than or equal to about 2000 IU/ml.
  • baseline total serum IgE level of the subject is equal to or greater than about 30 IU/ml and less than or equal to about 1850 IU/ml.
  • the method does not comprise concurrent oral immunotherapy with the food allergen.
  • the subject does not have asthma.
  • the subject does not have asthma, nasal polyps, or spontaneous urticaria.
  • the present disclosure relates to methods of preventing an allergic reaction to consumption of a food allergen in a human subject with one or more food allergies, the method comprising: administering by subcutaneous injection to the subject a pharmaceutical composition comprising omalizumab at a dose of 225 mg to 600 mg omalizumab and a dosing interval of every 2 weeks when body weight of the subject is greater than 25 kg and less than or equal to 150 kg, baseline total serum IgE level of the subject is equal to or greater than about 700 IU/ml and less than or equal to about 2000 IU/ml.
  • the body weight of the subject is greater than 25 kg and less than or equal to 90 kg, and the baseline total serum IgE level of the subject is equal to or greater than about 700 IU/ml and less than or equal to about 1850 IU/ml.
  • the method does not comprise concurrent oral immunotherapy with the food allergen.
  • the subject does not have asthma.
  • the subject does not have asthma, nasal polyps, or spontaneous urticaria.
  • the present disclosure relates to methods of preventing an allergic reaction to consumption of a food allergen in a human subject with one or more food allergies, the method comprising: administering by subcutaneous injection to the subject a pharmaceutical composition comprising omalizumab at a dose of 375 mg to 600 mg omalizumab and a dosing interval of every 2 weeks when body weight of the subject is greater than 25 kg and less than or equal to 150 kg, baseline total serum IgE level of the subject is equal to or greater than about 1300 IU/ml and less than or equal to about 1500 IU/ml.
  • the body weight of the subject is greater than 25 kg and less than or equal to 50 kg, and the baseline total serum IgE level of the subject is equal to or greater than about 1300 IU/ml and less than or equal to about 1500 IU/ml.
  • the method does not comprise concurrent oral immunotherapy with the food allergen.
  • the subject does not have asthma.
  • the subject does not have asthma, nasal polyps, or spontaneous urticaria.
  • the food allergy comprises an allergy to peanut, milk, egg, wheat, cashew, hazelnut, or walnut, or a combination thereof
  • the food allergen comprises peanut, milk, egg, wheat, cashew, hazelnut, or walnut, or a combination thereof.
  • the allergic reaction is a mild-to-moderate allergic reaction triggered by consumption of as little as about 100 mg to about 300 mg of the food allergen by the subject.
  • the allergic reaction is a moderate or moderate-to-severe allergic reaction triggered by consumption of as little as about 100 mg to about 300 mg of the food allergen by the subject.
  • the methods described herein permit the subject to consume a single dose of about 600 mg to about 1000 mg or more of the food allergen without triggering one or more dose-limiting symptoms or without triggering one or more moderate or severe dose-limiting symptoms. In some embodiments, the methods described herein permit the subject to consume a single dose of 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, or 1000 mg of the food allergen without triggering one or more mild, moderate, and/or severe dose-limiting symptom.
  • the one or more dose-limiting symptoms comprise one or more: skin: systemic hives, more than mild lip or face edema, pruritus causing protracted scratching, several areas of erythema pronounced erythema, and combinations thereof; and/or respiratory: throat tightness with or without hoarseness, persistent cough, wheezing with or without dyspnea, laryngeal edema, stridor, and combinations thereof; and/or gastrointestinal tract: moderate to severe abdominal pain, cramping, nausea, vomiting, and combinations thereof; and/or neurological: change in mental status; and/or circulatory: hypotension.
  • skin systemic hives, more than mild lip or face edema, pruritus causing protracted scratching, several areas of erythema pronounced erythema, and combinations thereof
  • respiratory throat tightness with or without hoarseness, persistent cough, wheezing with or without dyspnea, laryngeal edema, strid
  • without triggering dose-limiting symptoms in a subject treated with a dose of omalizumab comprises a lessening or lack of one or more dose-limiting symptoms. In some embodiments, without triggering dose-limiting symptoms in a subject treated with a dose of omalizumab comprises a lessening or lack of one or more moderate or severe dose-limiting symptoms. [0041] In some embodiments of the methods described herein, the method of treatment with a therapeutically effective amount of omalizumab results in the reduction or prevention of an allergic response by a subject having a food allergy after the subject is exposed to or consumes food containing an allergen to which that subject is allergic.
  • An allergic response can include but is not limited to several symptoms that are described in 11 sf-5598576 Attorney Docket No.: 146392067340 Table 1-1 as dose-limiting symptoms. These symptoms are categorized as mild, moderate, or severe. For example, a subject who has a food allergy will experience one or more symptoms described in Table 1-1 as a dose limiting response (mild, moderate, or severe) upon consumption of a food that contains the food allergen(s) to which the subject is allergic. In some embodiments, a subject who has a food allergy will experience one or more of the moderate or severe dose-limiting symptoms. Treatment according to the disclosure herein prevents an allergic reaction to a food allergen when after said treatment, the subject no longer experiences mild, moderate, and/or severe symptoms (Table 1-1).
  • Treatment according to the disclosure herein reduces an allergic reaction to a food allergen when after said treatment, the subject experiences one or more symptoms as listed in Table 1-1 to a lesser extent level of severity than if they had not received treatment with omalizumab.
  • an expert in the field of food allergy would recognize a reduction or prevention of an allergic reaction by omalizumab treatment as described herein.
  • an ordinarily skilled artisan would recognize a reduction or prevention of an allergic reaction by omalizumab treatment as described herein.
  • the methods described herein permit the subject to consume a single dose of about 600 mg to about 1000 mg or more of the food allergen without triggering an allergic reaction or dose-limiting symptom.
  • the methods described herein permit the subject to consume a single dose of about 600 mg to about 1000 mg or more of the food allergen while reducing the severity or frequency of an allergic reaction or dose-limiting symptom.
  • the methods of treatment described herein reduce dose- limiting symptoms a subject experiences after the subject is exposed to or consumes a food allergen to which the subject is allergic.
  • the methods reduce one or more of the dose-limiting symptoms experienced by the subject from severe to moderate, from severe to mild, or from moderate to mild.
  • the methods of treatment described herein prevent dose-limiting symptoms a subject experiences after the subject is exposed to a food allergen to which that subject is allergic.
  • the methods prevent a subject who, prior to any treatment with omalizumab, experienced severe, moderate, and/or mild dose-limiting symptoms after exposure to or consumption of an allergen to which the subject is allergic, from experiencing any severe dose-limiting symptoms, from experiencing any moderate dose-limiting symptoms, and/or from experiencing any mild dose-limiting symptoms.
  • the mild dose-limiting symptoms include limited or localized hives, swelling of the skin (e.g., mild lip edema), skin 12 sf-5598576 Attorney Docket No.: 146392067340 flushing (e.g., few areas of faint erythema), mild pruritus (e.g., occasional scratching), rhinorrhea (e.g., occasional sniffling or sneezing), nasal congestion, occasional cough, throat discomfort, mild abdominal (gastrointestinal) discomfort including but not limited to mild nausea with or without decreased activity, and/or isolated emesis thought to be secondary to gag.
  • swelling of the skin e.g., mild lip edema
  • skin 12 sf-5598576 Attorney Docket No.: 146392067340 flushing (e.g., few areas of faint erythema), mild pruritus (e.g., occasional scratching), rhinorrhea (e.g., occasional sniffling or sneezing), nasal congestion, occasional cough, throat
  • the moderate dose-limiting symptoms include systemic hives (e.g., numerous or widespread hives), swelling (e.g., significant lip or face edema), pruritus causing protracted scratching, more than a few areas of erythema or pronounced erythema. throat tightness without hoarseness, persistent cough, wheezing without dyspnea, persistent moderate abdominal pain/cramping/nausea with decreased activity, and/or vomiting.
  • systemic hives e.g., numerous or widespread hives
  • swelling e.g., significant lip or face edema
  • pruritus causing protracted scratching more than a few areas of erythema or pronounced erythema.
  • throat tightness without hoarseness persistent cough
  • wheezing without dyspnea persistent moderate abdominal pain/cramping/nausea with decreased activity
  • vomiting e.g., nausea, nausea, nausea, nausea, nausea, nausea, nausea, nausea
  • the severe dose-limiting symptoms include severe generalized urticarial, angioedema, and/or erythema, laryngeal edema, throat tightness with hoarseness, wheezing with dyspnea, stridor, severe abdominal pain and/or cramping, repetitive vomiting, change in mental status, and/or clinically significant hypotension.
  • the methods described herein reduce the allergic reaction in the subject when the subject is exposed to or consumes a food allergen to which the subject is allergic, wherein the subject, when administered a skin-prick test (SPT), experiences a wheal caused by the food allergen that is less than 4 mm, less than 3 mm, less than 2 mm, or less than 1 mm greater than a wheal caused by a saline control.
  • the methods described herein decrease serum free IgE concentration in the subject by at least 95%, 96%, 97%, 98%, or 99% relative to serum free IgE concentration prior to the serum free IgE concentration in the subject prior to the first dose of omalizumab.
  • the decrease occurs after the first, second, third, fourth, fifth, sixth, seventh, eighth, ninth, or tenth dose of omalizumab.
  • free IgE is measured no more than 3 months, 2 months, 1 month, 2 weeks, or 1 week prior to a first dose of omalizumab.
  • free IgE in human serum is measured using a solid phase immunoenzymetric assay (IEMA).
  • IEMA solid phase immunoenzymetric assay
  • free IgE in human serum is measured using a solid phase enzyme IEMA in which IgE is captured from serum using anti-human IgE antibody and detected with labeled-Fc ⁇ R1 ⁇ . 13 sf-5598576 Attorney Docket No.: 146392067340 [0046]
  • the methods described herein reduce the serum kilounits of allergen-specific IgE per liter (kUA/L) in the serum of the patient.
  • the treatment reduces allergen-specific by at least 95%, 96%, 97%, 98%, or 99% relative to serum allergen-specific IgE concentration prior to the serum free IgE concentration in the subject prior to the first dose of omalizumab.
  • the decrease occurs after the first, second, third, fourth, fifth, sixth, seventh, eighth, ninth, or tenth dose of omalizumab.
  • to serum allergen-specific IgE is measured no more than 3 months, 2 months, 1 month, 2 weeks, or 1 week prior to a first dose of omalizumab.
  • to serum allergen-specific IgE in human serum is measured using an ELISA.
  • the allergen-specific IgE is peanut, milk, wheat, soy, egg, cashew, or hazelnut-specific IgE.
  • the methods described herein reduce the likelihood the subject will require rescue treatment after consumption of the food allergen (e.g., a single dose of about 100 mg or more of peanut protein, and/or about 300 mg or more of milk, egg, wheat, cashew, hazelnut and/or walnut protein).
  • the rescue treatment comprises administration of an antihistamine or epinephrine.
  • the methods do not comprise concurrent oral immunotherapy to the food allergen. In other embodiments, the methods are useful in subjects who have failed prior oral immunotherapy.
  • the disclosure provides an anti-IgE antibody for use as a medicament.
  • the anti-IgE antibody is omalizumab or a monoclonal antibody which comprises CDR-H1 (GYSITSGY, set forth as SEQ ID NO:5), CDR-H2 (TYDGS, set forth as SEQ ID NO:6), CDR-H3 (GSHYFGHWHFAV, set forth as SEQ ID NO:7), CDR-L1 (RASQSVDYDGDSYMN, set forth as SEQ ID NO:8), CDR-L2 (AASYLES, set forth as SEQ ID NO:9) and CDR-L3 (QQSHEDPYT, set forth as SEQ ID NO:10).
  • the use is in the treatment of a human subject diagnosed with or having a food allergy to one or more allergens according to the embodiments described herein.
  • the use further comprises administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of the anti-IgE antibody such as omalizumab, e.g., as described herein.
  • the use does not comprise treating the subject with oral immunotherapy. 14 sf-5598576 Attorney Docket No.: 146392067340 [0050]
  • the disclosure provides use of an anti-IgE antibody in the manufacture or preparation of a medicament.
  • the anti-IgE antibody is omalizumab or a monoclonal antibody which comprises CDR-H1 (GYSITSGY, set forth as SEQ ID NO:5), CDR-H2 (TYDGS, set forth as SEQ ID NO:6), CDR-H3 (GSHYFGHWHFAV, set forth as SEQ ID NO:7), CDR-L1 (RASQSVDYDGDSYMN, set forth as SEQ ID NO:8), CDR-L2 (AASYLES, set forth as SEQ ID NO:9) and CDR-L3 (QQSHEDPYT, set forth as SEQ ID NO:10).
  • the medicament is for treatment of a food allergy to one or more allergens.
  • the medicament is for use in a method of treating the food allergy comprising administering to an individual having the food allergy to one or more allergens a therapeutically effective amount of the medicament such as a medicament comprising omalizumab. e.g., as described herein.
  • the use does not comprise treating the subject with oral immunotherapy i.
  • Subjects [0051]
  • the treatment methods of the present disclosure are intended for use in human subjects who are at least 6 years of age.
  • the subject is a child who is equal to or greater than 6 years of age and less than 12 years of age.
  • the subject an adolescent who is equal to or greater than 12 years of age and less than 18 years of age.
  • the subject is an adult who is equal to or greater 18 years of age.
  • Food allergens may include at least one of the major food allergens identified by the United States Food and Drug Administration such as milk, eggs, fish (e.g., bass, flounder, cod), crustacean shellfish (e.g., crab, lobster, shrimp), tree nuts (e.g., almonds, walnuts, pecans), peanuts, wheat, soybeans and sesame.
  • the food allergen is selected from at least one of the group consisting of peanut, milk, egg, wheat, cashew, hazelnut, and/or walnut protein.
  • the food allergy comprises an allergy to at least one food allergen.
  • a food allergen is any food that causes and allergic reaction.
  • a food allergen refers to the protein in the food that causes the allergic response.
  • the one or more food allergens include but are not limited to peanut, milk, egg, wheat, cashew, hazelnut, and/or walnut protein.
  • the subject has a food allergy to peanut.
  • the subject has a food allergy to peanut, and one or more of milk, egg, wheat, cashew, hazelnut and walnut.
  • the subject has a food allergy to peanut, 15 sf-5598576 Attorney Docket No.: 146392067340 and two or more of milk, egg, wheat, cashew, hazelnut and walnut. In some embodiments, the subject has a food allergy to peanut, and three or more of milk, egg, wheat, cashew, hazelnut, and walnut. [0053] In some embodiments, the subject has a food allergy to peanut, and four or more of milk, egg, wheat, cashew, hazelnut, and walnut. In some embodiments, the subject has a food allergy to peanut, and five or more of milk, egg, wheat, cashew, hazelnut, and walnut.
  • the subject has a food allergy to peanut, and milk, egg, wheat, cashew, hazelnut, and walnut.
  • the identification comprises a diagnosis of a food allergy by a physician.
  • the allergic reaction is characterized as a mild allergic reaction or dose-limiting symptom.
  • a “mild” allergic reaction includes manifestations in at least one of the skin, respiratory tract and gastrointestinal system (GI tract). Mild allergic reactions may manifest in the skin as limited or localized hives, swelling (e.g., mild lip edema), skin flushing (e.g., few areas of faint erythema) or mild pruritus (e.g., occasional scratching) and the like.
  • Mild allergic reactions may manifest in the respiratory tract as rhinorrhea (e.g., occasional sniffling or sneezing), nasal congestion, occasional cough, throat discomfort and the like. Mild allergic reactions may manifest in the GI tract as mild abdominal discomfort (including mild nausea with or without decreased activity), isolated emesis thought to be secondary to gag and the like. [0055] In some embodiments, the allergic reaction is characterized as a moderate allergic reaction or dose-limiting symptom. As used herein a “moderate” allergic reaction includes manifestations in at least one of the skin, respiratory tract and gastrointestinal system (GI tract).
  • GI tract gastrointestinal system
  • Moderate allergic reactions may manifest in the skin as systemic hives (e.g., numerous or widespread hives), swelling (e.g., significant lip or face edema), pruritus causing protracted scratching, more than a few areas of erythema or pronounced erythema and the like.
  • Moderate allergic reactions may manifest in the respiratory tract as throat tightness without hoarseness, persistent cough, wheezing without dyspnea and the like.
  • Moderate allergic reactions may manifest in the GI tract as persistent moderate abdominal pain/cramping/nausea with decreased activity, vomiting and the like.
  • the allergic reaction is characterized as a severe allergic reaction or dose-limiting symptom.
  • a “severe” allergic reaction includes manifestations in at least one of the skin, respiratory tract and gastrointestinal system (GI 16 sf-5598576 Attorney Docket No.: 146392067340 tract). Severe allergic reactions may manifest in the skin as severe generalized urticaria/angioedema/erythema and the like. Severe allergic reactions may manifest in the respiratory tract as laryngeal edema, throat tightness with hoarseness, wheezing with dyspnea, stridor and the like. Severe allergic reactions may manifest in the GI tract as severe abdominal pain/cramping/repetitive vomiting and the like.
  • severe allergic reaction may include neurological and circulatory manifestations such as change in mental status and clinically significant hypotension, respectively.
  • mild-to-moderate allergic reaction may be triggered by consumption of as little as about 100 mg of the food allergen by the subject prior to treatment using the disclosed methods.
  • mild-to-moderate allergic reaction may be triggered by consumption of as little as about 100 mg to about 300 mg of the food allergen by the subject prior to treatment using the disclosed methods.
  • peanut allergy is diagnosed by the presence of a clinical history of food allergy. In some embodiments, the peanut allergy is diagnosed or confirmed by one or more of: i.
  • allergy to a food allergen is diagnosed by one or more of: i.
  • positive SPT wheal at least 4 mm greater than saline control
  • positive food allergen-specific IgE unequal to or greater than 6 kUA/L
  • ELISA e.g., an ELISA
  • positive blinded OFC to the food allergen defined as experiencing dose-limiting symptoms at a single dose of about 100 mg to about 300 mg of the food allergen protein.
  • the subject experiences dose- limiting symptoms to a single dose of about 100 mg of peanut protein, about 100 mg to about 300 mg protein for any two or more of milk, egg, wheat, cashew, hazelnut, and/or walnut protein, and no dose-limiting symptoms to placebo (e.g., oat) at any single dose up to about 100 to about 300 mg protein prior to administration of a pharmaceutical composition comprising an anti-IgE antibody (e.g., omalizumab).
  • the subjects of the present disclosure do not have an IgE-mediated disorder that is not a food allergy (e.g., the only IgE-mediated disorder the subject is known to have is a food allergy).
  • the subjects of the present 17 sf-5598576 Attorney Docket No.: 146392067340 disclosure do not have asthma, nasal polyps, or chronic spontaneous urticaria at initiation of the treatment methods of the present disclosure.
  • the subjects of the present disclosure have not previously been diagnosed as having asthma, nasal polyps, or chronic spontaneous urticaria.
  • the subjects do not have asthma at initiation of the prophylactic methods of the present disclosure and have not previously been diagnosed as having asthma.
  • the subject has not been diagnosed with allergic rhinoconjunctivitis.
  • the subjects of the present disclosure have not received anti-IgE therapy prior to initiation of the treatment methods of the present disclosure.
  • the subjects of the present disclosure have not received anti-IgE therapy less than 6 months, 1 year, 18 months, or 2 years prior to initiation of the treatment methods of the present disclosure.
  • Dosing [0061] The pharmaceutical composition is administered to the subject at a specific omalizumab dose and dosing interval based on the body weight and baseline total serum IgE level of the subject. The specific dose and dosing interval (frequency) is determined based on the dosing table described in FIG. 2 herein. Accordingly, prior to administration of the pharmaceutical composition, a body weight and a baseline total serum IgE level of the subject is determined.
  • the omalizumab dose when the body weight of the subject is equal to or greater than 25 kg and less than or equal to 150 kg and the baseline total serum IgE level is equal to or greater than 30 IU/ml and less than or equal to 1500 IU/ml, the omalizumab dose is from 75 mg to 600 mg and the dosing interval is every two to four weeks. In some embodiments, body weight is determined at baseline (prior to a first dose). In some embodiments, the dose is 75 mg, wherein the body weight of the subject is greater than 25 kg and less than or equal to 40 kg and the total serum IgE level of the subject is equal to or greater than 30 IU/ml and less than or equal to 100 IU/ml.
  • the dose of omalizumab is administered every four weeks
  • the dose of omalizumab is 150 mg, wherein the body weight of the subject is greater than 40 kg and less than or equal to 90 kg and the total serum IgE level of the subject is equal to or greater than 30 IU/ml and less than or equal to 100 IU/ml; 150 mg, wherein the body weight of the subject is greater than 25 kg and less than or equal to 40 kg and the total serum IgE level of the subject is greater than 100 IU/ml and less than or equal to 18 sf-5598576 Attorney Docket No.: 146392067340 200 IU/ml; or 150 mg, wherein the body weight of the subject is greater than 25 kg and less than or equal to 30 kg and the total serum IgE level of the subject is greater than 200 IU/ml and less than or equal to 300 IU/ml.
  • the dose of omalizumab is administered every four weeks
  • the dose of omalizumab is: 225 mg, wherein the body weight of the subject is greater than 30 kg and less than or equal to 40 kg and the total serum IgE level of the subject is greater than 200 IU/ml and less than or equal to 300 IU/ml; or 225 mg, wherein the body weight of the subject is greater than 25 kg and less than or equal to 30 kg and the total serum IgE level of the subject is equal to or greater than 300 IU/ml and less than or equal to 400 IU/ml.
  • the dose of omalizumab is administered every four weeks.
  • the dose of omalizumab is: 300 mg, wherein the body weight of the subject is greater than 90 kg and less than or equal to 150 kg and the total serum IgE level of the subject is equal to or greater than 30 IU/ml and less than or equal to 100 IU/ml; 300 mg, wherein the body weight of the subject is greater than 40 kg and less than or equal to 90 kg and the total serum IgE level of the subject is greater than 100 IU/ml and less than or equal to 200 IU/ml; 300 mg, wherein the body weight of the subject is greater than 40 kg and less than or equal to 60 kg and the total serum IgE level of the subject is greater than 200 IU/ml and less than or equal to 300 IU/ml; 300 mg, wherein the body weight of the subject is greater than 30 kg and less than or equal to 40 kg and the total serum IgE level of the subject is greater than 300 IU/ml and less than or equal to 400 IU/ml; 300 mg, wherein the body weight of the subject
  • the dose of omalizumab is administered every four weeks.
  • the dose of omalizumab is: 450 mg, wherein the body weight of the subject is greater than 90 kg and less than or equal to 125 kg and the total serum IgE level of the subject is greater than 100 IU/ml and less than or equal to 200 IU/ml; 450 mg, wherein the body weight of the subject is greater than 60 kg and less than or equal to 90 kg and the total serum IgE level of the subject is greater than 200 IU/ml and less than or equal to 300 IU/ml; 450 mg, wherein the body weight of the subject is greater than 40 kg and less than or equal to 70 kg and the total serum IgE level of the subject is greater than 300 IU/ml and less 19 sf-5598576 Attorney Docket No.: 146392067340 than or equal to 400 IU/ml; 450 mg, wherein the body weight of the subject is greater than 30 kg and less than or equal
  • the dose of omalizumab is administered every four weeks.
  • the dose of omalizumab is: 600 mg, wherein the body weight of the subject is greater than125 kg and less than or equal to 155 kg and the total serum IgE level of the subject is greater than 100 IU/ml and less than or equal to 200 IU/ml; 600 mg, wherein the body weight of the subject is greater than 90 kg and less than or equal to 125 kg and the total serum IgE level of the subject is greater than 200 IU/ml and less than or equal to 300 IU/ml; 600 mg, wherein the body weight of the subject is greater than 70 kg and less than or equal to 90 kg and the total serum IgE level of the subject is greater than 300 IU/ml and less than or equal to 400 IU/ml; 600 mg, wherein the body weight of the subject is greater than 50 kg and less than or equal to 70 kg and the total serum IgE level of the subject is greater than 400 IU/ml
  • the dose of omalizumab is administered every four weeks. In some embodiments, the dose of omalizumab is: 225 mg, wherein the body weight of the subject is greater than 25 kg and less than or equal to 30 kg and the total serum IgE level of the subject is greater than 600 IU/ml and less than or equal to 900 IU/ml. In some embodiments, the dose of omalizumab is administered every two weeks.
  • the dose of omalizumab is: 300 mg, wherein the body weight of the subject is greater than 30 kg and less than or equal to 40 kg and the total serum IgE level of the subject is greater than 700 IU/ml and less than or equal to 900 IU/ml; or 300 mg, wherein the body weight of the subject is greater than 25 kg and less than or equal to 30 kg and the total serum IgE level of the subject is greater than 900 IU/ml and less than or equal to 1200 IU/ml.
  • the dose of omalizumab is administered every four weeks.
  • the dose of omalizumab is: 375 mg, wherein the body weight of the subject is greater than 125 kg and less than or equal to 150 kg and the total serum IgE level of the subject is greater than 200 IU/ml and less than or equal to 300 IU/ml; 375 mg, wherein the body weight of the subject is greater than 70 kg and less than or equal to 90 kg and the total serum IgE level of the subject is greater than 400 IU/ml and less than or equal to 500 IU/ml; 375 mg, wherein the body weight of the subject is greater than 60 kg and less than or equal to 70 kg and the total serum IgE level of the subject is greater than 500 IU/ml and less than or equal to 600 IU/ml;- 375 mg, wherein the body weight of the subject is greater than 50 kg and less than or equal to 60 kg and the total serum IgE level of the subject is greater than 600 IU
  • the dose of omalizumab is administered every two weeks.
  • the dose of omalizumab is: 450 mg, wherein the body weight of the subject is greater than 90 kg and less than or equal to 125 kg and the total serum IgE level of the subject is greater than 300 IU/ml and less than or equal to 400 IU/ml; 450 mg, wherein the body weight of the subject is greater than 70 kg and less than or equal to 90 kg and the total serum IgE level of the subject is greater than 500 IU/ml and less than or equal to 600 IU/ml; 450 mg, wherein the body weight of the subject is greater than 60 kg and less than or equal to 80 kg and the total serum IgE level of the subject is greater than 600 IU/ml and less than or equal to 700 IU/ml; 450 mg, wherein the body weight of the subject is greater than 50 kg and less than or equal to 70 kg and the total serum IgE level of the subject is greater than 700 IU
  • the dose of omalizumab is administered every two weeks.
  • the dose of omalizumab is: 525 mg, wherein the body weight of the subject is greater than 125 kg and less than or equal to 155 kg and the total serum IgE level of the subject is greater than 300 IU/ml and less than or equal to 400 IU/ml; 525 mg, wherein the body weight of the subject is greater than 90 kg and less than or equal to 125 kg and the total serum IgE level of the subject is greater than 400 IU/ml and less than or equal to 500 IU/ml; 525 mg, wherein the body weight of the subject is greater than 80 kg and less than or equal to 90 kg and the total serum IgE level of the subject is greater than 600 IU/ml and less than or equal to 700 IU/ml; 525 mg, wherein the body weight of the subject is greater than 70 kg and less than or equal to 80 kg and the total serum IgE level of the subject is greater than 700
  • the dose of omalizumab is administered every two weeks.
  • the dose of omalizumab administered is: 600 mg, wherein the body weight of the subject is greater than 125 kg and less than or equal to 150 kg and the total serum IgE level of the subject is greater than 400 IU/ml and less than or equal to 500 IU/ml; 600 mg, wherein the body weight of the subject is greater than 90 kg and less than or equal to 125 kg and the total serum IgE level of the subject is greater than 500 IU/ml and less than or equal to 600 IU/ml; 600 mg, wherein the body weight of the subject is greater than 80 kg and less than or equal to 90 kg and the total serum IgE level of the subject is greater than 700 IU/ml and less than or equal to 800 IU/ml; 600 mg, wherein the body weight of the subject is greater than 70 kg and less than or equal to 70 kg and the total serum IgE level of the subject is greater than 800 IU/m
  • the dose of omalizumab is administered every two weeks.
  • body weight is determined at baseline (prior to administration of the first dose of the pharmaceutical composition).
  • total serum IgE level concentration is determined at baseline (prior to administration of the first dose of the pharmaceutical composition).
  • determining the baseline body weight and the baseline total serum IgE level of the subject is done no more than 3 months, 2 months, 1 month, 2 weeks, or 1 week prior to administration of a first dose of the pharmaceutical composition, preferably no more than 7, 6, 5, 4, 3, 2 or 1 day prior to administration of a first dose of the pharmaceutical composition.
  • body weight of the subject is further determined prior to administration of a subsequent dose (post-baseline body weight) of the pharmaceutical composition.
  • the body weight is a post-baseline body weight of the subject, which is determined no more than two weeks prior to administration of each subsequent dose of the pharmaceutical composition, preferably no more than 7, 6, 5, 4, 3, 2 or 1 day prior to administration of each subsequent dose of the pharmaceutical composition. It is understood that a subject may gain or lose body weight during of the course of treating the subject with omalizumab for a food allergy. Accordingly, the dose amount and/or frequency may change during the course of treatment.
  • the dose of omalizumab may be changed relative to the first dose and in accordance with the dosing table of FIG. 2, wherein a subsequent dose (any dose after the first dose) is selected based on the body weight of the subject which is determined after the first dose but prior to the subsequent dose.
  • the selection of the dose may not consider a change in serum total IgE levels from the baseline serum total IgE levels.
  • the methods of treatment further comprise determining the body weight of the subject prior to administration of a subsequent dose of omalizumab to obtain a current body weight of the subject, wherein the subsequent dose administered to the subject is based on the current body weight of the subject at a time after the first dose and prior to the subsequent dose, and wherein the dose is based on the body weight of the subject prior to the subsequent dose and on the serum total IgE levels 23 sf-5598576 Attorney Docket No.: 146392067340 determined prior to the first dose of omalizumab and according to the dosing table shown in FIG. 2.
  • the subsequent dose is administered within 1 day, 1 week, 2 weeks, or 4 weeks of the determination of the current body weight of the subject.
  • the methods further comprise determining the age of the subject prior to administration of the first dose of omalizumab.
  • total serum IgE is measured by an enzyme-linked immunosorbent assay (ELISA).
  • ELISA enzyme-linked immunosorbent assay
  • the baseline total serum IgE level is equal to or greater than 30 IU/ml and less than or equal to 2000 IU/ml. In some embodiments, the baseline total serum IgE level is from about 30 IU/ml to about 700 IU/ml.
  • the baseline total serum IgE level is from about 600 IU/ml to about 1850 IU/ml. In some embodiments, the baseline total serum IgE level is equal to or greater than 30 IU/ml and less than or equal to 1500 IU/ml. In some embodiments, the baseline total serum IgE level is from about 30 IU/ml to about 700 IU/ml. In some embodiments, the baseline total serum IgE level is from about 700 IU/ml to about 1500 IU/ml. [0065] In certain embodiments, the dosing interval (also referred to herein as dosing frequency) is about once every 2 to 4 weeks and the duration of administration is at least 16 weeks to 12 months in length.
  • the dosing interval is every 2 weeks. In some embodiments, the dosing interval is every 4 weeks. In some embodiments, the duration of administration is at least about 16 to 20 weeks in length (e.g., from 4 to 10 total doses), at least about 16 to 40 weeks (e.g., from 4 to 20 total doses), or at least about 24 to 40 weeks (e.g., from about 6 to 20 total doses). In some embodiments, the duration of administration is at least about 10 to 12 months in length (e.g., from 10 to 24 total doses). iii.
  • compositions of the present disclosure comprising an anti- IgE antibody, such as omalizumab, are administered by subcutaneous injection to a human subject diagnosed with or suffering from one or more food allergies.
  • the methods of the present disclosure may include repeated administration of the pharmaceutical composition comprising an anti-IgE antibody, such as omalizumab.
  • the duration of administration is until the subject is no longer diagnosed with food allergy.
  • the duration of treating is at least 16 to 20 weeks in length. In some embodiments, the duration of treating is at least 40 to 48 weeks in length.
  • the duration of treating is at least about 10 months to about 12 months in 24 sf-5598576 Attorney Docket No.: 146392067340 length.
  • the duration of treating can be at least about 16 weeks, 18 weeks, 20 weeks, 22 weeks, 24 weeks, 26 weeks, 28 weeks, 30 weeks, 32 weeks, 34 weeks, 36 weeks, 38 weeks, or 40 weeks.
  • the duration of treating can be at least about 6 months, 8 months, about 10 months, or 12 months.
  • kits comprise: i) a pharmaceutical composition comprising an anti-IgE antibody, such as omalizumab; and ii) instructions for administration of the pharmaceutical composition by subcutaneous injection to a human subject suffering from one or more food antibodies to prevent an allergic reaction triggerable by consumption of a food allergen by the human subject, wherein the pharmaceutical composition is administered at an anti-IgE antibody (e.g., omalizumab) dose and a dosing interval determined from measurement of body weight and baseline total serum IgE level of the subject.
  • the pharmaceutical composition is an aqueous solution further comprising L- arginine hydrochloride, L-histidine, and L-histidine hydrochloride monohydrate.
  • the pharmaceutical composition further comprises sucrose.
  • the pharmaceutical composition contains omalizumab at a concentration of about 150 g/L in 0.02 M histidine, 0.2 M arginine-HCl, and 0.04 % polysorbate 20, pH 6.
  • the pharmaceutical composition is present in a pre-filled syringe.
  • the pharmaceutical composition is a lyophilized powder present in a vial, and the kit further comprises instructions for reconstituting the lyophilized powder in water for injection. 25 sf-5598576 Attorney Docket No.: 146392067340 III. Enumerated Embodiments 1.
  • a method of treating a human subject diagnosed with a food allergy to one or more food allergens comprising: administering by subcutaneous injection once every two or four weeks to the subject a pharmaceutical composition comprising omalizumab at a dose of from 75 mg to 600 mg, wherein prior to administration of a first dose of omalizumab to the subject, body weight of the subject is greater than 25 kg and less than or equal to 150 kg and total serum IgE level of the subject is greater than or equal to 30 IU/ml and less than or equal to 2,000 IU/ml, wherein the method does not comprise concurrent oral immunotherapy with the food allergen, and wherein the subject has not been diagnosed with asthma prior to administration of the first dose of omalizumab.
  • the method of embodiment 1, wherein the dose of omalizumab administered about every four weeks is: 75 mg when the body weight of the subject is greater than 25 kg and less than or equal to 40 kg and the total serum IgE level of the subject is equal to or greater than 30 IU/ml and less than or equal to 100 IU/ml. 3.
  • the method of embodiment 1, wherein the dose of omalizumab administered about every four weeks is: 150 mg when the body weight of the subject is greater than 40 kg and less than or equal to 90 kg and the total serum IgE level of the subject is equal to or greater than 30 IU/ml and less than or equal to 100 IU/ml; 150 mg when the body weight of the subject is greater than 25 kg and less than or equal to 40 kg and the total serum IgE level of the subject is greater than 100 IU/ml and less than or equal to 200 IU/ml; and/or 150 mg when the body weight of the subject is greater than 25 kg and less than or equal to 30 kg and the total serum IgE level of the subject is greater than 200 IU/ml and less than or equal to 300 IU/ml.
  • the dose of omalizumab administered about every four weeks is: 225 mg when the body weight of the subject is greater than 30 kg and less than or equal to 40 kg and the total serum IgE level of the subject is greater than 200 IU/ml and less than or 26 sf-5598576 Attorney Docket No.: 146392067340 equal to 300 IU/ml; and/or 225 mg when the body weight of the subject is greater than 25 kg and less than or equal to 30 kg and the total serum IgE level of the subject is equal to or greater than 300 IU/ml and less than or equal to 400 IU/ml. 5.
  • the dose of omalizumab administered about every four weeks is: 300 mg when the body weight of the subject is greater than 90 kg and less than or equal to 150 kg and the total serum IgE level of the subject is equal to or greater than 30 IU/ml and less than or equal to 100 IU/ml 300 mg when the body weight of the subject is greater than 40 kg and less than or equal to 90 kg and the total serum IgE level of the subject is greater than 100 IU/ml and less than or equal to 200 IU/ml; 300 mg when the body weight of the subject is greater than 40 kg and less than or equal to 60 kg and the total serum IgE level of the subject is greater than 200 IU/ml and less than or equal to 300 IU/ml; 300 mg when the body weight of the subject is greater than 30 kg and less than or equal to 40 kg and the total serum IgE level of the subject is greater than 300 IU/ml and less than or equal to 400 IU/ml; 300 mg when the body weight of the subject is greater than 30 kg and
  • the dose of omalizumab administered about every four weeks is: 450 mg when the body weight of the subject is greater than 90 kg and less than or equal to 125 kg and the total serum IgE level of the subject is greater than 100 IU/ml and less than or equal to 200 IU/ml; 450 mg when the body weight of the subject is greater than 60 kg and less than or equal to 90 kg and the total serum IgE level of the subject is greater than 200 IU/ml and less than or equal to 300 IU/ml; 450 mg when the body weight of the subject is greater than 40 kg and less than or equal to 27 sf-5598576 Attorney Docket No.: 146392067340 70 kg and the total serum IgE level of the subject is greater than 300 IU/ml and less than or equal to 400 IU/ml; 450 mg when the body weight of the subject is greater than 30 kg and less than or equal to 50 kg and the total serum IgE level of the subject is greater than 400 IU/
  • the dose of omalizumab administered about every two weeks is: 300 mg when the body weight of the subject is greater than 30 kg and less than or equal to 40 kg and the total serum IgE level of the subject is greater than 700 IU/ml and less than or equal to 900 IU/ml; and/or 300 mg when the body weight of the subject is greater than 25 kg and less than or equal to 30 kg and the total serum IgE level of the subject is greater than 900 IU/ml and less than or equal to 1200 IU/ml. 10.
  • the dose of omalizumab administered about every two weeks is: 375 mg when the body weight of the subject is greater than 125 kg and less than or equal to 150 kg and the total serum IgE level of the subject is greater than 200 IU/ml and less than or equal to 300 IU/ml; 375 mg when the body weight of the subject is greater than 70 kg and less than or equal to 90 kg and the total serum IgE level of the subject is greater than 400 IU/ml and less than or equal to 500 IU/ml; 375 mg when the body weight of the subject is greater than 60 kg and less than or equal to 70 kg and the total serum IgE level of the subject is greater than 500 IU/ml and less than or equal to 600 IU/ml; 375 mg when the body weight of the subject is greater than 50 kg and less than or equal to 60 kg and the total serum IgE level of the subject is greater than 600 IU/ml and less than or equal to 700 IU/ml; 375 mg when the body weight of the subject is greater
  • the dose of omalizumab administered about every two weeks is: 450 mg when the body weight of the subject is greater than 90 kg and less than or equal to 125 kg and the total serum IgE level of the subject is greater than 300 IU/ml and less than or equal to 400 IU/ml; 450 mg when the body weight of the subject is greater than 70 kg and less than or equal to 90 kg and the total serum IgE level of the subject is greater than 500 IU/ml and less than or equal to 600 IU/ml; 450 mg when the body weight of the subject is greater than 60 kg and less than or equal to 80 kg and the total serum IgE level of the subject is greater than 600 IU/ml and less than or equal to 700 IU/ml; 450 mg when the body weight of the subject is greater than 50 kg and less than or equal to 70 kg and the total serum IgE level of the subject is greater than 700 IU/ml and less than or equal to 800 IU/ml; 450 mg when the body weight of the subject is greater
  • the dose of omalizumab administered about every two weeks is: 525 mg when the body weight of the subject is greater than 125 kg and less than or equal to 155 kg and the total serum IgE level of the subject is greater than 300 IU/ml and less than or equal to 400 IU/ml; 525 mg when the body weight of the subject is greater than 90 kg and less than or equal to 125 kg and the total serum IgE level of the subject is greater than 400 IU/ml and less than or equal to 500 IU/ml; 30 sf-5598576 Attorney Docket No.: 146392067340 525 mg when the body weight of the subject is greater than 80 kg and less than or equal to 90 kg and the total serum IgE level of the subject is greater than 600 IU/ml and less than or equal to 700 IU/ml; 525 mg when the body weight of the subject is greater than 70 kg and less than or equal to 80 kg and the total serum IgE level of the subject is greater than 700 IU/ml; 525
  • the method of embodiment 1, wherein the dose of omalizumab administered about every two weeks is: 600 mg when the body weight of the subject is greater than 125 kg and less than or equal to 150 kg and the total serum IgE level of the subject is greater than 400 IU/ml and less than or equal to 500 IU/ml; 600 mg when the body weight of the subject is greater than 90 kg and less than or equal to 125 kg and the total serum IgE level of the subject is greater than 500 IU/ml and less than or equal to 600 IU/ml; 600 mg when the body weight of the subject is greater than 80 kg and less than or equal to 90 kg and the total serum IgE level of the subject is greater than 700 IU/ml and less than or equal to 800 IU/ml; 600 mg when the body weight of the subject is greater than 70 kg and less than or equal to 70 kg and the total serum IgE level of the subject is greater than 800 IU/ml and less than or equal to 900 IU/ml; 600 mg when the body weight of
  • any one of embodiments 1-17 wherein the subject has not been diagnosed with nasal polyps or chronic spontaneous urticaria prior to administration of the first dose of omalizumab.
  • the one or more food allergies comprise an allergy to peanut, milk, egg, wheat, cashew, hazelnut, or walnut, or a combination thereof, and the food allergen comprises peanut, milk, egg, wheat, cashew, hazelnut, or walnut, or a combination thereof.
  • the subject has two or more food allergies. 21.
  • the one or more food allergies are multiple food allergies comprising an allergy to peanut and allergies to two or more of milk, egg, wheat, cashew, hazelnut and walnut. 22.
  • a moderate-to-severe allergic reaction to a food comprises onset of one or more symptoms after consumption of about 100 mg or from 10 mg to 100 mg of peanut protein, and/or consumption of about 300 mg or from 30 mg to 300 mg of milk, egg, wheat, cashew, hazelnut and/or walnut protein, and wherein the one or more symptoms comprise one or more: skin: systemic hives, more than mild lip or face edema, pruritus causing protracted scratching, several areas of erythema pronounced erythema, and combinations thereof; and/or respiratory: throat tightness with or without hoarseness, persistent cough, wheezing with or without dyspnea, laryngeal edema, stridor, and combinations thereof; and/or gastrointestinal tract: moderate to severe abdominal pain, cramping, nausea, vomiting, and combinations thereof;
  • preventing the allergic reaction permits the subject to consume a single dose of about 600 mg or from 600 mg to 1800 mg of peanut protein, and/or a single dose of about 1000 mg or from 1000 mg to 3000 mg of milk, egg, wheat, cashew, hazelnut and/or walnut protein without triggering dose-limiting symptoms.
  • preventing the allergic reaction permits the subject to consume a single dose of about 1000 mg or from 1000 mg to 3000 mg of peanut, milk, egg, wheat, cashew, hazelnut and/or walnut protein without triggering dose- limiting symptoms.
  • preventing the allergic reaction permits the subject to consume a single dose of about 2000 mg or from 2000 mg to 6000 mg 33 sf-5598576 Attorney Docket No.: 146392067340 of peanut, milk, egg, wheat, cashew, hazelnut and/or walnut protein without triggering dose- limiting symptoms.
  • preventing the allergic reaction reduces likelihood that the subject will require treatment with antihistamine or epinephrine after consuming a single dose of about 100 mg or from 100 mg to 300 mg of peanut protein, and/or a single dose of about 300 mg or from 300 mg to 900 mg of milk, egg, wheat, cashew, hazelnut and/or walnut protein.
  • duration of the administering step is at least 10 to 12 months in length.
  • duration of the administering step is at least 10 to 12 months in length.
  • determining the total serum IgE level is done with an enzyme-linked immunosorbent assay.
  • the pharmaceutical composition is an aqueous solution further comprising L-arginine hydrochloride, L-histidine, and L-histidine hydrochloride monohydrate.
  • the pharmaceutical composition further comprises sucrose.
  • a kit comprising: i) a pharmaceutical composition comprising omalizumab; and ii) instructions for administering the pharmaceutical composition according to the method of any one of embodiments 1-37. 39.
  • Omalizumab for use in a method of treating a human subject diagnosed with a food allergy to one or more food allergens, the method comprising: administering by subcutaneous injection once about every two weeks to the subject a pharmaceutical composition comprising omalizumab at a dose of from 75 mg to 600 mg, wherein prior to administration of a first dose of omalizumab to the subject, body weight of the subject is greater than 25 kg and less than or equal to 150 kg and total serum IgE level of the subject is equal to or greater than 30 IU/ml and less than or equal to 2,000 IU/ml, and wherein the method does not comprise concurrent oral immunotherapy with the food allergen. 43.
  • omalizumab at a dose of from 75 mg to 600 mg in the manufacture of a medicament for treating a human subject diagnosed with a food allergy to one or more food allergens, wherein the medicament is to be administered by subcutaneous injection once about every two weeks to the subject when prior to administration of a first dose of omalizumab to the subject, body weight of the subject is greater than 25 kg and less than or equal to 150 kg and total serum IgE level of the subject is equal to or greater than 30 IU/ml and less than or equal to 2,000 IU/ml, and wherein the medicament is not administered in combination with oral immunotherapy with the food allergen.
  • This Example describes Screening, Stage 1, and Stage 1 Open-Label Extension (OLE) of a 3-stage Phase 3 clinical study (OUtMATCH) to test use of omalizumab for treatment of human subjects having allergies to one or more foods.
  • Stage 1 is directed to use of omalizumab as a monotherapy to treat food allergy patients, i.e., without receiving oral immunotherapy and while practicing food avoidance.
  • FIG. 1 A flow chart of Stage 1 of the study design is shown in FIG. 1, which details the screening stage using oral food challenges, Stage 1 employing treatment and re-testing with oral food challenges and Stage 1 OLE employing continued treatment and re-testing with oral food challenges.
  • Stage 1 Participants were those who experienced dose-limiting symptoms after receiving a single dose of ⁇ 100 mg of peanut protein, and ⁇ 300 mg protein for each of the other two foods, or those who experienced no dose-limiting symptoms after receiving placebo at any single dose up to 300 mg protein during the Screening DBPCFC were randomized 2:1 to 16-20 weeks of treatment with omalizumab or placebo for omalizumab per the omalizumab dosing table of FIG. 2.
  • Stage 1 Open-Label Extension The first 60 participants who completed Stage 1 were selected to participate in the OLE. Each participant received 24-28 weeks of 37 sf-5598576 Attorney Docket No.: 146392067340 open label omalizumab. After 24-28 weeks of treatment in the OLE, each participant completed a DBPCFC consisting of placebo and each of their three specific foods to a cumulative dose of 8044 mg protein of each food.
  • Biomarker objectives To compare immunological responses after treatment with either omalizumab or placebo for omalizumab, and to determine whether immunological responses can be used to predict the ability to consume foods without dose-limiting systems during a DBPCFC after treatment with either omalizumab or placebo for omalizumab. For the OLE, to assess immunological responses at the end of either 24 or 40 weeks of treatment with omalizumab.
  • Endpoints [0080] Primary endpoint: Consumption of a single dose of ⁇ 600 mg of peanut protein without dose-limiting symptoms during the DBPCFC at the end of Stage 1. A participant who met this endpoint would be considered a “success” while a participant who did not meet this endpoint would be considered a “failure”.
  • Other secondary endpoints Consumption of a single dose of ⁇ 600 mg, ⁇ 1000 mg, ⁇ 1 dose of 2000 mg, or 2 doses of 2000 mg protein of each food, at least two foods, or all three foods without dose-limiting symptoms during the DBPCFC at the end of Stage 1 (except for those endpoints already defined by the primary and key secondary endpoints in Stage 1); and number of foods consumed at a single dose of ⁇ 600 mg, ⁇ 1000 mg, ⁇ 1 dose of 2000 mg, or 2 doses of 2000 mg protein of each food without dose-limiting symptoms during the DBPCFC at the end of Stage 1.
  • Safety endpoints an adverse event related to study therapy regimen received during Stage 1 or received during Stage 1 OLE.
  • QoL was assessed between Week 0 in Stage 1, at the first DBPCFC visit at the end of Stage 1, and for those participants who move to Stage 1 OLE, between Week 0 in Stage 1 and the first omalizumab injection visit in Stage 1 OLE, the first DBPCFC visit at the end of Stage 1 OLE, and the last DBPCFC visit at the end of Stage 1 OLE.
  • QoL was measured by the Food Allergy Quality of Life Questionnaire – Parent Form (FAQLQ-PF) for participants aged 0-12 years; Food Allergy Quality of Life Questionnaire – Child Form (FAQLQ-CF) for children/adolescents aged 8-12 years; Food Allergy Quality of Life Questionnaire – Teenager Form (FAQLQ-TF) for participants aged 13-17 years; and Food Allergy Quality of Life Questionnaire – Adult Form (FAQLQ-AF) (Flokstra-de Blok, B.M.J. (2014). Food Allergy Quality of Life Questionnaires (FAQLQ). In: Michalos, A.C. (eds) Encyclopedia of Quality of Life and Well-Being Research.
  • Biomarker exploratory endpoints Total immunoglobulin E (IgE), total free IgE, allergen-specific IgE, allergen-specific immunoglobulin G4 (IgG4), allergen-specific immunoglobulin A (IgA), IgG4/IgE ratio, basophil activation, and skin prick tests (SPTs). Allergen-specific immune biomarkers (allergen-specific IgE, allergen-specific IgG4, allergen-specific IgA, basophil activation, and SPTs) were evaluated using peanut and the two other participant-specific foods.
  • Immune biomarkers were analyzed at the following times: first Screening DBPCFC visit; first DBPCFC visit at the end of Stage 1; and first DBPCFC visit at the end of Stage 1 OLE (for those participants who move to Stage 1 OLE).
  • Mechanistic exploratory endpoints including dendritic cell and T cell assays, were measured at the following times: first Screening DBPCFC visit and first DBPCFC visit at the end of Stage 1.
  • ImmunoCAP TM Total IgE marketed by ThermoFisher Scientific was used to measure circulating IgE in serum and plasma (EDTA and heparin) samples according to the manufacturer’s instructions, from participants prior to initiation of therapy with omalizumab or placebo.
  • ImmunoCAP TM Total IgE is a quantitative enzyme linked immunosorbent assay, which measures circulating IgE within a range of 2 to 5000 kU/L (2 to 5000 IU/mL or about 2.4 ng/mL).
  • a person having ordinary skill in the art can develop or use alternative assays, including ELISAs, to measure levels of human IgE in the serum or plasma of a subject.
  • Treatments [0089] Omalizumab: Omalizumab is a recombinant humanized immunoglobulin G1 monoclonal antibody that binds to the Fc ⁇ R1 binding epitope of human IgE, preventing human IgE from binding to its specific high-affinity receptors on mast cells and basophils.
  • Omalizumab is approved by the European Commission and US FDA for patients with moderate-severe asthma ⁇ 6 years of age and for patients with chronic idiopathic urticaria ⁇ 12 years of age. Omalizumab is not currently approved for treating food allergy in patients of any age.
  • Placebo for omalizumab The composition of the placebo for omalizumab was the same as the composition of the active study drug without the omalizumab. 40 sf-5598576 Attorney Docket No.: 146392067340 [0091] Omalizumab and placebo for omalizumab were administered as a subcutaneous injection according to the omalizumab dosing table of FIG. 2.
  • Patient Selection Criteria • 1 year to less than 56 years of age at Screening. • Peanut allergy and: 1. Positive SPT ( ⁇ 4 mm wheal greater than saline control) to peanut; 2. Positive peanut IgE ( ⁇ 6 kUA/L) at Screening or within three months of Screening, determined by ImmunoCap TM ; and 3. Positive blinded oral food challenge (OFC) to peanut during the Screening DBPCFC, defined as experiencing dose-limiting symptoms (see Table 1-1) at a single dose of ⁇ 100 mg of peanut protein.
  • SPT ⁇ 4 mm wheal greater than saline control
  • Positive peanut IgE ⁇ 6 kUA/L
  • OFC Positive blinded oral food challenge
  • Cashew, hazelnut, or walnut ⁇ Positive SPT ( ⁇ 4 mm wheal greater than saline control) to food or positive food specific IgE ( ⁇ 6 kUA/L) at Screening or within three months of Screening, determined by ImmunoCap TM ; and ⁇ Positive blinded OFC to food during the Screening DBPCFC, defined as experiencing dose-limiting symptoms (see Table 1-1) at a single dose of ⁇ 300 mg of food protein. • Body weight (as measured at Screening) and total serum IgE level (as measured within three months of Screening) suitable for omalizumab dosing.
  • the DBPCFC consisted of four blinded oral food challenges (OFCs): three active OFCs (peanut and two additional foods) and one placebo OFC (oat).
  • the DBPCFC was conducted in up to four separate visits.
  • the food challenges were prepared from allergen food protein flours (active) and oat flour (placebo), respectively.
  • Food challenges were performed under medical supervision with emergency medications immediately available.
  • the maximum cumulative dose for each blinded OFC during the Screening DBPCFC was 444 mg of protein.
  • the maximum single dose given was 100 mg of peanut protein with the final single 300 mg dose consisting of placebo.
  • Stage 1 assessed whether 16-20 weeks of treatment with omalizumab versus placebo for omalizumab would increase the proportion of participants who consumed each of the foods under study without dose-limiting symptoms, as assessed by a DBPCFC.
  • Participants who experienced dose-limiting symptoms to a single dose of ⁇ 100 mg of peanut protein, ⁇ 300 mg protein for each of the other two foods, and no dose-limiting symptoms to placebo at any single dose up to 300 mg protein during the Screening DBPCFC were randomized 2:1 to 16-20 weeks of treatment with omalizumab or placebo for omalizumab per the dosing table provided in FIG. 2.
  • This dosing table was specifically designed to accommodate the food allergy patient population characteristics (i.e., lower body weight and/or higher baseline total serum IgE level) of the OUtMATCH clinical trial.
  • each participant (and/or a parent or guardian) was instructed to strictly avoid all foods to which they were allergic.
  • Each randomized participant visited the clinic every two or four weeks, depending on assigned dosing frequency, for subcutaneous injection of omalizumab or placebo for omalizumab. Each participant was observed for at least two hours after the first three injections and for at least 30 minutes after all subsequent injections to assess for the development of adverse events (AEs).
  • AEs adverse events
  • each participant was subjected to a DBPCFC according to the dosing schedule of Table 1-3, consisting of placebo and each of their three specific foods to a cumulative dose of 6044 mg protein of each food. The DBPCFC took place within a maximum period of 28 days from the last treatment.
  • Stage 1 OLE Each participant received 24-28 weeks of open label omalizumab, before being subjected to a DBPCFC according to the dosing schedule of Table 1-4, consisting of placebo or each of their three specific foods to a cumulative dose of 8044 mg protein of each food. The DBPCFC took place within a maximum period of 28 days from the last treatment. Each participant who did not complete Stage 1 OLE (i.e., does not complete all four blinded OFCs comprising the DBPCFC at the end of OLE) was withdrawn from the study and asked to attend an Early Discontinuation Visit.
  • Stage 1 of the study met pre-defined thresholds for significance for both primary and key secondary endpoints.
  • the interim results were reviewed by the Data Safety Monitoring Board, who recommended stopping Stage 1 with no further enrollment due to efficacy of omalizumab monotherapy.
  • 180 participants were enrolled, including 177 pediatric participants and 3 adult participants.
  • Topline clinical study results from the interim analysis provide strong evidence that omalizumab reduces the risk of having an allergic reaction as a consequence of oral exposure to food allergens.
  • Both primary and key secondary endpoints achieved pre-defined statistical significance based on the proportion of participants without dose-limiting symptoms during the Double-Blind Placebo-Controlled Food Challenge (DBPCFC) at the end of Stage 1.
  • DBPCFC Double-Blind Placebo-Controlled Food Challenge
  • Baseline demographics were generally balanced across treatment arms. The mean age across treatment arms was 7.8 years for the pediatric participants: 37% were ⁇ 6 years of age, 37.6% were age 6 to ⁇ 12 years, and 25.5% were age 12 to ⁇ 18 years.
  • the study met the primary endpoint and achieved statistical significance on the proportion of participants who could consume a single dose of ⁇ 600 mg of peanut protein without dose-limiting symptoms during the DBPCFC at the end of Stage 1.
  • 68.2% of participants passed the DBPCFC compared to 5.5% in placebo ( ⁇ : 62.7%, OR: 37.14, p ⁇ 0.00001).
  • the study also met all the key secondary endpoints.
  • omalizumab treatment is associated with a higher probability of passing the DBPCFC at the 47 sf-5598576 Attorney Docket No.: 146392067340 end of treatment and that the response from omalizumab administration is durable.
  • 72.1% of participants had no dose-limiting symptoms with ⁇ 600 mg of peanut protein at the end of the Stage 1 OLE.
  • 55.6% had no dose-limiting symptoms with ⁇ 1000 mg of cashew
  • 76.0% of participants had no dose-limiting symptoms with ⁇ 1000 mg of milk
  • 77.8% had no dose-limiting symptoms with ⁇ 1000 mg of egg.
  • Results also showed efficacy in the ability of treated subjects to consume doses of multiple foods without experiencing dose-limiting symptoms. Participants in the omalizumab and placebo groups were compared for their ability to consume a single dose of ⁇ 600 mg, a single dose ⁇ 1000 mg, ⁇ 1 dose of 2000 mg, or 2 doses of 2000 mg of at least 2 of their participant-specific tested foods without dose-limiting symptoms during the DBPCFC at the end of Stage 1.
  • Participants in the omalizumab and placebo for omalizumab groups were compared for their ability to consume a single dose of ⁇ 600 mg, a single dose of ⁇ 1000 mg, ⁇ 1 dose of 2000 mg, or 2 doses of 2000 mg of all 3 foods tested without dose-limiting symptoms during the DBPCFC at the end of Stage 1.
  • Odds ratios were calculated comparing the consumption of a higher number of foods without dose-limiting symptoms during the DBPCFCs at the end of Stage 1 between participants in the omalizumab and placebo for omalizumab groups. Whether challenges were with a single dose of ⁇ 600 mg of each food, ⁇ 1000 mg of each food, ⁇ 1 dose of 2000 mg of each food, or 2 doses of 2000 mg of each food, participants in the omalizumab group were able to consume more foods than participants in the placebo group.
  • Stage 1 Adverse Events (AE) [0115] In Stage 1, a majority of the participants (112 participants, 67.9%) experienced at least one treatment-emergent AE (TEAE) for a total of 346 TEAEs. In the omalizumab group, 69 (62.7%) participants experienced a combined total of 216 TEAEs. In the placebo group, 43 (78.2%) participants experienced 130 TEAEs.
  • TEAE treatment-emergent AE
  • SOCs system organ classes in which TEAEs were experienced by ⁇ 15% of the participants were: Infections and Infestations (45 participants, 27.3%); Immune System Disorders (42 participants, 25.5%); General disorders and administration site conditions (34 participants, 20.6%); and Respiratory, thoracic, and mediastinal disorders (27 participants, 16.4%).
  • stage 1 OLE AEs [0121] In the OLE, 42 (71.2 %) participants experienced 126 TEAEs.

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Abstract

La présente divulgation concerne des méthodes et des kits pour traiter ou prévenir une réaction allergique à un allergène alimentaire consommé par un sujet humain ayant une ou plusieurs allergies alimentaires. En particulier, la présente divulgation concerne des thérapies prophylactiques comprenant l'administration d'un anticorps anti-IgE à une dose spécifique à un sujet humain qui est allergique à un ou plusieurs allergènes alimentaires.
PCT/US2023/070637 2023-07-05 2023-07-20 Thérapie à base d'anticorps anti-ige pour allergies alimentaires multiples Pending WO2025010085A1 (fr)

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