Methods for treating active eosinophilic esophagitis

Patent metadata

Field	Value
Publication number	US-11053309-B2
Application number	US-201816054583-A
Country	US
Kind code	B2
Filing date	Aug 3, 2018
Priority date	Aug 4, 2017
Publication date	Jul 6, 2021
Grant date	Jul 6, 2021

Abstract

The present invention provides methods for treating, preventing or reducing the severity of active eosinophilic esophagitis. In certain embodiments, the present invention provides methods of increasing esophageal distensibility. The methods of the present invention comprise administering to a subject in need thereof a therapeutic composition comprising an interleukin-4/interleukin-13 (IL-4/IL-13) pathway inhibitor such as an anti-IL-4R antibody.

First claim

What is claimed is:

1. A method of increasing esophageal distensibility in a patient having eosinophilic esophagitis (EoE), the method comprising:
(a) selecting a patient having EoE, who has a baseline of ≥15 eosinophils per high powered field (hpf) in the esophagus, wherein the patient has been treated previously with a proton pump inhibitor (PPI) and has had at least one prior esophageal dilation; and
(b) administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising an interleukin-4/interleukin-13 (IL-4/IL-13) pathway inhibitor, wherein the IL-4/IL-13 pathway inhibitor is an antibody or antigen-binding fragment thereof that binds IL-4Rα, wherein the antibody or antigen-binding fragment thereof comprises the heavy chain complementarity determining regions (HCDRs) of a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 1 and the light chain complementarity determining regions (LCDRs) of a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 2.

2. The method of claim 1 , wherein the patient is ≥12 years of age.

3. The method of claim 2 , wherein the patient is ≥18 years of age.

4. The method of claim 1 , wherein the patient has a concurrent disease or condition selected from the group consisting of food allergy, allergic rhinitis, non-food allergy, asthma, chronic sinusitis, hives, atopic dermatitis, and allergic conjunctivitis.

5. The method of claim 1 , wherein the patient has an elevated level of at least one biomarker selected from the group consisting of eotaxin-3, periostin, serum IgE (total and allergen-specific), IL-13, IL-5, serum thymus and activation regulated chemokine (TARC), thymic stromal lymphopoietin (TSLP), serum eosinophilic cationic protein (ECP), and eosinophil-derived neurotoxin (EDN).

6. The method of claim 1 , wherein administration of the IL 4/IL-13 pathway inhibitor results in an increase of at least 10% from baseline in esophageal distensibility, as measured by a functional lumen imaging probe.

7. The method of claim 1 , wherein the IL-4/IL-13 pathway inhibitor is administered at a dose of about 50 to about 600 mg.

8. The method of claim 1 , wherein the IL-4/IL-13 pathway inhibitor is administered at a dose of about 300 mg.

9. The method of claim 8 , wherein each dose is administered one week or two weeks after the immediately preceding dose.

10. The method of claim 1 , wherein the IL-4/IL-13 pathway inhibitor is administered at an initial dose followed by one or more secondary doses, wherein each secondary dose is administered 1 to 4 weeks after the immediately preceding dose.

11. The method of claim 10 , wherein the initial dose comprises 50-600 mg of the IL-4/IL-13 pathway inhibitor.

12. The method of claim 10 , wherein each secondary dose comprises 25-400 mg of the IL-4/IL-13 pathway inhibitor.

13. The method of claim 10 , wherein the initial dose comprises 600 mg of the IL-4/IL-13 pathway inhibitor, and each secondary dose comprises 300 mg of the IL-4/IL-13 pathway inhibitor.

14. The method of claim 13 , wherein each secondary dose is administered one week or two weeks after the immediately preceding dose.

15. The method of claim 1 , wherein the patient exhibits an allergic reaction to a food allergen contained in a food item selected from the group consisting of a dairy product, egg, wheat, soy, corn, fish, shellfish, peanut, a tree nut, beef, chicken, oat, barley, pork, green beans, apple and pineapple.

16. The method of claim 1 , wherein the patient exhibits an allergic reaction to a non-food allergen derived from one of dust, pollen, mold, plant, cat, dog or insect.

17. The method of claim 1 , wherein the IL-4/IL-13 pathway inhibitor is administered in combination with a second therapeutic agent or therapy, wherein the second therapeutic agent or therapy is selected from the group consisting of an IL-1beta inhibitor, an IL-5 inhibitor, an IL-9 inhibitor, an IL-13 inhibitor, an IL-17 inhibitor, an IL-25 inhibitor, a TNFalpha inhibitor, an eotaxin-3 inhibitor, an IgE inhibitor, a prostaglandin D2 inhibitor, an immunosuppressant, a topical corticosteroid, an oral corticosteroid, a systemic corticosteroid, an inhaled corticosteroid, a glucocorticoid, a proton pump inhibitor, a NSAID, esophagus dilation, allergen removal, and diet management.

18. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 3, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 4, an HCDR3 comprising the amino acid sequence of SEQ ID NO: 5, an LCDR1 comprising the amino acid sequence of SEQ ID NO: 6, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 7, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 8.

19. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises an HCVR comprising the amino acid sequence of SEQ ID NO: 1, and an LCVR comprising the amino acid sequence of SEQ ID NO: 2.

20. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof 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.

21. The method of claim 1 , wherein the IL-4/IL-13 pathway inhibitor is dupilumab or a bioequivalent thereof.

22. The method of claim 1 , wherein the IL-4/IL-13 pathway inhibitor is administered subcutaneously.

Assignees

• Regeneron Pharma
• Sanofi Biotechnology

Inventors

• Radin Allen
• Hamilton Jennifer D
• Mannent Leda

Classifications

• A61P1/00

  Drugs for disorders of the alimentary tract or the digestive system · CPC title

• A61K2039/577

  tolerising response · CPC title

• C07K2317/21

  from primates, e.g. man · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K16/2866 Primary

  against receptors for cytokines, lymphokines, interferons · CPC title