Methods for treating eosinophilic esophagitis by administering an IL-4R inhibitor

Patent metadata

Field	Value
Publication number	US-2016152718-A1
Application number	US-201615017664-A
Country	US
Kind code	A1
Filing date	Feb 7, 2016
Priority date	Jul 11, 2013
Publication date	Jun 2, 2016
Grant date	—

Abstract

The present invention provides methods for treating, preventing or reducing the severity of eosinophilic esophagitis. The methods of the present invention comprise administering to a subject in need thereof a therapeutic composition comprising an interleukin-4 receptor (IL-4Rα) inhibitor such as an anti-IL-4Rα antibody.

First claim

What is claimed is:

1 . A method of treating or ameliorating at least one symptom or indication of eosinophilic esophagitis (EoE) comprising:
(a) selecting a patient with a history of diagnosis of EoE wherein the patient has ≧15 eosinophils per high powered field (hpf) from a esophageal biopsy specimen; and (b) administering to the patient one or more doses of a pharmaceutical composition comprising a therapeutically effective amount of an interleukin-4 receptor (IL-4R) inhibitor.

2 . The method of claim 1 , wherein the symptom or indication of EoE is selected from the group consisting of eosinophilic inflammation of the esophagus, thickening of the esophageal wall, food refusal, vomiting, abdominal pain, heartburn, regurgitation, dysphagia, and food impaction.

3 . The method of claim 1 , wherein the symptom or indication of EoE is an elevated level of an EoE-associated biomarker.

4 . The method of claim 3 , wherein the EoE-associated biomarker is 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).

5 . The method of claim 1 , wherein the patient, prior to or at the time of administration of the pharmaceutical composition, has or is diagnosed with a disease or disorder selected from the group consisting of atopic dermatitis, asthma, allergic rhinitis and food allergies.

6 . 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.

7 . The method of claim 1 , wherein the patient has elevated peripheral eosinophil counts of ≧300 cells/μL.

8 . The method of claim 1 , wherein the patient has elevated serum IgE level of ≧50 kU/L.

9 . The method of claim 1 , wherein the pharmaceutical composition is administered subcutaneously to the patient.

10 . The method of claim 1 , wherein each dose of the pharmaceutical composition comprises 50-600 mg of the IL-4R inhibitor.

11 . The method of claim 10 , wherein each dose comprises 300 mg of the IL-4R inhibitor.

12 . The method of claim 1 , wherein step (b) comprises: administering an initial dose of the pharmaceutical composition to the patient; followed by administering one or more subsequent doses of the pharmaceutical composition to the patient, wherein each subsequent dose is administered to the patient one week after the immediately preceding dose.

13 . The method of claim 12 , wherein the initial dose comprises 600 mg and each subsequent dose comprises 300 mg of the IL-4R inhibitor.

14 . The method of claim 1 , wherein the IL-4R 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 corticosteroid, a glucocorticoid, a proton pump inhibitor, a NSAID, allergen removal and diet management.

15 . The method of claim 1 , wherein the IL-4R inhibitor is an antibody or antigen-binding fragment thereof that binds IL-4Rα and prevents the interaction of IL-4 and/or IL-13 with a type 1 or type 2 IL-4 receptor.

16 . The method of claim 15 , wherein the antibody or antigen-binding fragment thereof prevents the interaction of IL-4 and IL-13 with both type 1 and type 2 IL-4 receptors.

17 . The method of claim 16 , wherein the antibody or antigen-binding fragment thereof comprises the heavy chain complementarity determining regions (HCDRs-HCDR1, HCDR2 and HCDR3) 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-LCDR1, LCDR2 and LCDR3) of a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 2.

18 . The method of claim 16 , wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 3; HCDR2 comprises the amino acid sequence of SEQ ID NO: 4; HCDR3 comprises the amino acid sequence of SEQ ID NO: 5; LCDR1 comprises the amino acid sequence of SEQ ID NO: 6; LCDR2 comprises the amino acid sequence of SEQ ID NO: 7; and LCDR3 comprises the amino acid sequence of SEQ ID NO: 8.

19 . The method of claim 18 , wherein the HCVR comprises the amino acid sequence of SEQ ID NO: 1 and the LCVR comprises the amino acid sequence of SEQ ID NO: 2.

20 . The method of claim 1 , wherein the IL-4R inhibitor is dupilumab or a bioequivalent thereof.

Assignees

• Regeneron Pharma

Inventors

• Kostic Ana
• Kelly Ludmila
• Liu Xia
• Classon Brendan J
• Radin Allen

Classifications

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61P1/06

  Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia · CPC title

• A61P1/04

  for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants · CPC title

• A61P11/06

  Antiasthmatics · CPC title