JPWO2021195530A5 - - Google Patents

Claims (33)

A pharmaceutical composition comprising an interleukin-4-receptor (IL-4R) antagonist for use in a method of treating atopic dermatitis (AD) or improving AD-related parameters in a subject, the composition comprising:
The method includes:
(a) Selecting subjects with moderate to severe or severe AD that is not adequately controlled by topical AD medications, where the subjects are between 6 months and older than 6 years of age; and (b) administering to the subject one or more doses of an IL-4R antagonist;
The IL-4R antagonist is an anti-IL-4R antibody or antigen-binding fragment thereof comprising three HCDRs (HCDR1, HCDR2 and HCDR3) and three LCDRs (LCDR1, LCDR2 and LCDR3), where HCDR1 is SEQ ID NO: HCDR2 contains the amino acid sequence of SEQ ID NO: 4, HCDR3 contains the amino acid sequence of SEQ ID NO: 5, LCDR1 contains the amino acid sequence of SEQ ID NO: 6, and LCDR2 contains the amino acid sequence of SEQ ID NO: 7. , LCDR3 comprises the amino acid sequence of SEQ ID NO: 8. The pharmaceutical composition according to claim 1, wherein the subject is a subject with severe AD. 3. The pharmaceutical composition of claim 1 or 2, wherein the subject is inadequately responsive to treatment with moderate or higher potency topical corticosteroids (TCS). The pharmaceutical composition according to any one of claims 1 to 3, wherein the subject has previously been administered a systemic AD therapeutic. The pharmaceutical composition according to any one of claims 1 to 4, wherein the subject is 6 months or more and less than 2 years old. The pharmaceutical composition according to any one of claims 1 to 4, wherein the subject is aged 2 to under 6 years. The target is,
(i) Have a baseline Investigator Global Assessment (IGA) score = 4;
(ii) have a baseline Eczema Area and Severity Index (EASI) score of ≧21; and/or (iii) have a baseline body surface area (BSA) affected by AD of ≧15%.
The pharmaceutical composition according to any one of claims 1 to 6. Pharmaceutical composition according to any one of claims 1 to 7, wherein the IL-4R antagonist is administered subcutaneously at a dose of 3 mg/kg. A pharmaceutical composition according to any one of claims 1 to 7, wherein the IL-4R antagonist is administered subcutaneously at a dose of at least 6 mg/kg. The pharmaceutical composition according to claim 9, wherein the IL-4R antagonist is administered subcutaneously at a dose of 6 mg/kg. The pharmaceutical composition according to any one of claims 1 to 7, wherein the IL-4R antagonist is administered subcutaneously in an amount that provides a total exposure of the IL-4R antagonist in the subject of at least 130 days mg/L. The pharmaceutical composition of any one of claims 1 to 11, comprising administering multiple doses of an IL-4R antagonist to a subject. 13. The pharmaceutical composition of claim 12, wherein the IL-4R antagonist is administered subcutaneously in an amount such that the total exposure of the IL-4R antagonist in the subject is at least 130 days.mg/L for a period of at least two weeks. . The pharmaceutical composition according to any one of claims 1 to 13, wherein the IL-4R antagonist is administered to a subject once a week or once every two weeks. The pharmaceutical composition of any one of claims 1 to 14, wherein the subject has a concurrent atopic or allergic condition selected from the group consisting of allergic rhinitis, asthma, food allergy, allergic conjunctivitis, urticaria, chronic rhinosinusitis, nasal polyps, and eosinophilic esophagitis. 16. The pharmaceutical composition according to claim 15, wherein the subject has a food allergy. The pharmaceutical composition according to any one of claims 1 to 16, wherein the IL-4R antagonist is administered in combination with a topical AD treatment drug. 18. The pharmaceutical composition of claim 17, wherein the topical AD treatment is a medium potency TCS or a low potency TCS. Pharmaceutical composition according to any one of claims 1 to 18, wherein treatment with an IL-4R antagonist results in a decrease in the level of one or more type 2 inflammatory biomarkers in the subject compared to baseline values. thing. The pharmaceutical composition of claim 19, wherein treatment with an IL-4R antagonist results in a decrease in serum TARC and/or serum total IgE levels in a subject compared to baseline values. Treatment with an IL-4R antagonist:
(i) a reduction from baseline in IGA score to achieve an IGA score of 0 or 1 by week 4 after administration of the first dose of the IL-4R antagonist;
(ii) at least a 50% reduction from baseline in EASI score (EASI-50) by week 3 after administration of the first dose of the IL-4R antagonist;
(iii) at least a 75% reduction from baseline in EASI score (EASI-75) by 3 weeks after administration of the first dose of the IL-4R antagonist;
(iv) a decrease in the percentage of BSA affected by AD to less than 40% BSA by 3 weeks after administration of the first dose of the IL-4R antagonist; and (v) a 35% decrease from baseline in BSA affected by AD by 3 weeks after administration of the first dose of the IL-4R antagonist;
The pharmaceutical composition according to any one of claims 1 to 20, which results in improvement of one or more AD-related parameters selected from the group consisting of: 22. A pharmaceutical composition according to any one of claims 1 to 21, wherein the AD-related parameter is determined based on a caregiver-reported assessment. The pharmaceutical composition of any one of claims 1 to 22, wherein treatment with an IL-4R antagonist results in an improvement in caregiver-reported peak itch Numeric Rating Scale (NRS) score. 24. A pharmaceutical composition according to any one of claims 1 to 23, wherein treatment with an IL-4R antagonist results in an improvement in itch. 25. The pharmaceutical composition of claim 24, wherein the improvement in itch is assessed by caregiver-reported peak itch NRS score. A claim wherein the anti-IL-4R antibody or antigen-binding fragment thereof comprises a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 1 and a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 2. The pharmaceutical composition according to any one of items 1 to 25. 27. The pharmaceutical composition according to any one of claims 1 to 26, wherein the anti-IL-4R antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10. 28. A pharmaceutical composition according to any one of claims 1 to 27, wherein the IL-4R antagonist is dupilumab or a biological equivalent thereof. The pharmaceutical composition according to any one of claims 1 to 28, wherein the IL-4R antagonist is contained in a container selected from the group consisting of a glass vial, a syringe, a pre-filled syringe, a pen delivery device, and an autoinjector. The pharmaceutical composition according to claim 29, wherein the IL-4R antagonist is contained in a prefilled syringe. 31. The pharmaceutical composition of claim 30, wherein the prefilled syringe is a single dose prefilled syringe. 30. The pharmaceutical composition of claim 29, wherein the IL-4R antagonist is contained in an autoinjector. 30. The pharmaceutical composition of claim 29, wherein the IL-4R antagonist is contained in a pen-shaped delivery device.