Methods for treating or preventing asthma by administering an IL-4R antagonist

Patent metadata

Field	Value
Publication number	US-11845800-B2
Application number	US-201715627669-A
Country	US
Kind code	B2
Filing date	Jun 20, 2017
Priority date	Aug 21, 2012
Publication date	Dec 19, 2023
Grant date	Dec 19, 2023

Abstract

The present invention provides methods for treating or preventing asthma and associated conditions in a patient. The methods of the present invention comprise administering to a subject in need thereof a therapeutic composition comprising an interleukin-4 receptor (IL-4R) antagonist, such as an anti-IL-4R antibody.

First claim

What is claimed is:

1. A method for reducing the incidence of one or more asthma exacerbations in a subject suffering from severely persistent asthma comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of an antibody or an antigen-binding fragment thereof that specifically binds to interleukin-4 receptor (IL-4R),
wherein the antibody or antigen-binding fragment thereof comprises heavy chain complementarity determining region (HCDR) sequences of SEQ ID NOs:148, 150 and 152, and comprises light chain complementarity determining region (LCDR) sequences of SEQ ID NOs:156, 158 and 160, and
wherein the pharmaceutical composition is an add-on maintenance treatment administered in combination with a background therapy, and
wherein the subject has an eosinophilic phenotype comprising a blood eosinophil level of at least 300 cells per microliter, and/or a sputum eosinophil level of at least 3%.

2. The method of claim 1 , wherein the asthma exacerbation is selected from the group consisting of:
(a) a 30% or greater reduction from baseline in morning peak expiratory flow (PEF) on two consecutive days;
(b) six or more additional reliever puffs of albuterol or levalbuterol in a 24 hour period (compared to baseline) on two consecutive days; and
(c) a deterioration of asthma requiring:
systemic (oral and/or parenteral) steroid treatment, or
(ii) an increase in inhaled corticosteroids to at least 4 times the last dose received prior to discontinuation, or
(iii) hospitalization.

3. The method of claim 1 , wherein the pharmaceutical composition comprises 75 mg to 600 mg of the antibody or antigen-binding fragment thereof.

4. The method of claim 1 , wherein the pharmaceutical composition is administered to the subject at a dosing frequency of once every two weeks.

5. A method for improving one or more asthma-associated parameter(s) in a subject suffering from severely persistent asthma comprising administering to the subject a pharmaceutical composition comprising an a therapeutically effective amount of antibody or an antigen-binding fragment thereof that specifically binds to interleukin-4 receptor (IL-4R), wherein the antibody or antigen-binding fragment thereof comprises heavy chain complementarity determining region (HCDR) sequences of SEQ ID NOs:148, 150 and 152, and comprises light chain complementarity determining region (LCDR) sequences of SEQ ID NOs:156, 158 and 160, and wherein the pharmaceutical composition is an add-on maintenance treatment administered in combination with a background therapy, wherein the improvement in an asthma-associated parameter is selected from the group consisting of:
(a) an increase from baseline of forced expiratory volume in 1 second (FEV1) of at least 0.10 L;
(b) an increase from baseline of morning peak expiratory flow rate (AM PEF) of at least 10.0 L/min;
(c) an increase from baseline of evening peak expiratory flow rate (PM PEF) of at least 1.0 L/min;
(d) a decrease from baseline of daily albuterol or levalbuterol use of at least 1 inhalation/day;
(e) a decrease from baseline of five-item Asthma Control Questionnaire (ACQ5) score of at least 0.5 points;
(f) a decrease from baseline of nighttime awakenings (no. of times per night) measured daily of at least 0.2 times per night; and
(g) a decrease from baseline of 22-item Sino-Nasal Outcome Test (SNOT-22) score of at least 5 points, and
wherein the subject has an eosinophilic phenotype comprising a blood eosinophil level of at least 300 cells per microliter, and/or a sputum eosinophil level of at least 3%.

6. The method of claim 5 , wherein the pharmaceutical composition comprises 75 mg to 600 mg of the antibody or antigen-binding fragment thereof.

7. The method of claim 1 , wherein the background therapy is selected from the group consisting of: a TNF inhibitor, an IL-1 inhibitor, an IL-5 inhibitor, an IL-8 inhibitor, an IgE inhibitor, a leukotriene inhibitor, a corticosteroid, a methylxanthine, an NSAID, nedocromil sodium, cromolyn sodium, a long-acting beta2 agonist and an anti-fungal agent or any combinations thereof.

8. A method for treating or reducing the incidence of asthma exacerbations or improving one or more asthma-associated parameter(s) in a subject suffering from severely persistent asthma comprising administering to the subject a single initial dose of a pharmaceutical composition comprising a therapeutically effective amount of an antibody or an antigen-binding fragment thereof that specifically binds to interleukin-4 receptor (IL-4R) followed by one or more secondary doses of the pharmaceutical composition,
wherein the antibody or antigen-binding fragment thereof comprises heavy chain complementarity determining region (HCDR) sequences of SEQ ID NOs:148, 150 and 152, and comprises light chain complementarity determining region (LCDR) sequences of SEQ ID NOs:156, 158 and 160, and
wherein the pharmaceutical composition is an add-on maintenance treatment administered in combination with a background therapy, and
wherein the subject has an eosinophilic phenotype comprising a blood eosinophil level of at least 300 cells per microliter, and/or a sputum eosinophil level of at least 3%.

9. The method of claim 8 , wherein each of the initial dose and the secondary doses of the pharmaceutical composition comprises 75 mg to 600 mg of the antibody or antigen-binding fragment.

10. The method of claim 9 , wherein each of the secondary doses is administered 1 to 8 weeks after the immediately preceding dose.

11. A method of treating severely persistent asthma in a subject comprising:
(a) selecting a subject that has severely persistent asthma and exhibits one or both of a blood eosinophil level of at least 300 cells per microliter and a sputum eosinophil level of at least 3%; and
(b) administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of an antibody or antigen-binding fragment thereof that specifically binds to interleukin-4-receptor (IL-4R), wherein the antibody or antigen-binding fragment thereof comprises heavy chain complementarity determining region (HCDR) sequences of SEQ ID NOs:148, 150 and 152, and comprises light chain complementarity determining region (LCDR) sequences of SEQ ID NOs:156, 158 and 160, and wherein the pharmaceutical composition is an add-on maintenance treatment administered in combination with a background therapy.

12. A method of reducing or eliminating a severely persistent asthma patient's dependence on a background therapy comprising inhaled corticosteroids (ICS) and/or long-acting beta-agonists (LABA) for the treatment of one or more asthma exacerbations comprising:
(a) selecting a patient who has severely persistent asthma that is partially controlled or uncontrolled with a background asthma therapy comprising an ICS, a LABA, or a combination thereof;
(b) administering to the patient a defined dose of a therapeutically effective amount of an antibody or antigen-binding fragment thereof that specifically binds to interleukin-4-receptor (IL-4R) at a defined frequency for an initial treatment period while maintaining the patient's background asthma therapy for the initial treatment period, wherein the antibody or antigen-binding fragment thereof comprises heavy chain complementarity determining region (HCDR) sequences of SEQ ID NOs:148, 150 and 152, and comprises light chain complementarity determining region (LCDR) sequences of SEQ ID NOs:156, 158 and 160; and
(c) gradually reducing or eliminating the dosage of ICS and/or LABA administered to the patient over the course of a subsequent treatment period while continuing to administer the antib

Assignees

• Sanofi Biotechnology
• Regeneron Pharma

Inventors

• Ardeleanu Marius
• Gandhi Namita A
• Graham Neil
• Kirkesseli Stephane C
• Kundu Sudeep
• Rocklin Ross E
• Radin Allen
• Weinstein Steven P
• Hamilton Jennifer Davidson
• Ming Jeffrey

Classifications

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• A61P11/06

  Antiasthmatics · CPC title

• C07K16/2866 Primary

  against receptors for cytokines, lymphokines, interferons · CPC title

• A61K39/3955

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title

• A61K39/39541

  against normal tissues, cells · CPC title