BR-122026002779-A2 - Uses of an antibody or antigen-binding fragment thereof that specifically binds to the interleukin-4 receptor for the treatment of asthma, composition, medicine, pen-type administration device, autoinjector for subcutaneous administration, standard syringe and needle for subcutaneous or intravenous administration, and kit.

BR122026002779A2BR 122026002779 A2BR122026002779 A2BR 122026002779A2BR-122026002779-A2

Abstract

Methods for treating or preventing asthma in a pediatric individual. Methods are provided that comprise administering to a pediatric individual in need a therapeutic composition comprising an interleukin-4 receptor (IL-4R) antagonist, such as an anti-IL-4R antibody or antigen-binding fragment thereof.

Inventors

Christine Xu
Bolanle AKINLADE
Nikhil Amin
Marcella Ruddy

Assignees

SANOFI BIOTECHNOLOGY
REGENERON PHARMACEUTICALS, INC.

Dates

Publication Date: 20260317
Application Date: 20211004
Priority Date: 20210831

Claims (14)

1. Use of an antibody or an antigen-binding fragment thereof that specifically binds to the interleukin-4 receptor (IL-4R), characterized in that it is in the manufacture of a medicament, composition or product for treating an individual with asthma, wherein the antibody or antigen-binding fragment thereof comprises three heavy chain CDR sequences comprising SEQ ID NOs: 3, 4 and 5, respectively, and three light chain CDR sequences comprising SEQ ID NOs: 6, 7 and 8, respectively, wherein: (a) the individual has a body weight greater than 30 kg, the individual is between 6 years and less than 12 years old, and the antibody or antigen-binding fragment thereof is comprised in the medicament, composition or product with a content of approximately 200 mg; or (b) the individual has a body weight of 30 kg or less and the antibody or antigen-binding fragment thereof is included in the medicinal product, composition or product with a content of approximately 100 mg; or (c) the individual has a body weight greater than 30 kg and the antibody or antigen-binding fragment thereof is included in the medicinal product, composition or product with a content of approximately 200 mg.
2. Use according to claim 1(a), characterized in that the medicine, composition or product is manufactured to be useful for administering the antibody or antigen-binding fragment to the individual as an initial dose followed by one or more secondary doses, optionally wherein the initial dose is about 200 mg and each secondary dose is about 200 mg, or wherein the asthma is uncontrolled persistent asthma, or wherein the asthma is uncontrolled moderate to severe asthma, or wherein the individual has asthma with an eosinophilic phenotype that includes a baseline blood eosinophil count greater than or equal to 300 cells^L, or wherein the individual has asthma with a Type 2 inflammatory phenotype that includes one or both baseline blood eosinophil counts greater than or equal to 150 cells^L and a baseline FeNO greater than or equal to 20 ppb.
3. Use according to claim 1(b), characterized in that the medicine, composition or product is manufactured to be useful for administering the antibody or antigen-binding fragment to the subject as an initial dose followed by one or more secondary doses, optionally wherein the initial dose is about 100 mg and each secondary dose is about 100 mg, or wherein the subject is 6 years to less than 12 years old, or wherein the subject has a body weight of at least 16 kg, or wherein the asthma is uncontrolled persistent asthma, or wherein the asthma is uncontrolled moderate to severe asthma, or wherein the subject has asthma with an eosinophilic phenotype that includes a baseline blood eosinophil count greater than or equal to 300 cells/L, or wherein the subject has asthma with a Type 2 inflammatory phenotype that includes one or both baseline blood eosinophil counts greater than or equal to 150 cells/L and a baseline FeNO greater than or equal to 20 ppb.
4. Use according to claim 1(c), characterized in that the medicine, composition or product is manufactured to be useful for administering the antibody or antigen-binding fragment to the individual as an initial dose followed by one or more secondary doses, optionally wherein the initial dose is about 200 mg and each secondary dose is about 200 mg, or wherein the individual has asthma with an eosinophilic phenotype that includes a baseline blood eosinophil count greater than or equal to 300 cells^L, or wherein the individual has a Type 2 inflammatory phenotype that includes one or both baseline blood eosinophil counts greater than or equal to 150 cells^L and a baseline FeNO greater than or equal to 20 ppb.
5. Use of an antibody or antigen-binding fragment that specifically binds to the interleukin-4 receptor (IL-4R), characterized in that it is in the manufacture of a medicament, composition or product for treating an individual aged between 6 years and less than 12 years with asthma and/or uncontrolled moderate to severe asthma, wherein the antibody or antigen-binding fragment thereof comprises three heavy chain CDR sequences comprising SEQ ID NOs: 3, 4 and 5, respectively, and three light chain CDR sequences comprising SEQ ID NOs: 6, 7 and 8, respectively, wherein: (a) the individual has a body weight of 30 kg or less and the antibody or antigen-binding fragment thereof is comprised in the medicament, composition or product with a content of approximately 100 mg; or (b) wherein the medicinal product, composition or product is manufactured to be useful for administering the antibody or antigen-binding fragment thereof to the individual as an initial dose followed by one or more secondary doses, wherein each secondary dose is to be administered 1 to 4 weeks after the immediately preceding dose, and wherein: (i) for an individual with a body weight <30 kg, the initial dose of the antibody or antigen-binding fragment thereof is 100 mg and each secondary dose is 100 mg; or (ii) for an individual with a body weight >30 kg, the initial dose of the antibody or antigen-binding fragment is 200 mg and each secondary dose is 200 mg; or (c) wherein the individual has a body weight of 30 kg or less, and wherein the medicine, composition or product is manufactured to be useful for administering the antibody or antigen-binding fragment thereof to the individual at a dose of about 300 mg every four weeks (q4w), or wherein the medicine, composition or product is manufactured to be useful for administering the antibody or antigen-binding fragment thereof to the individual at a dose of about 300 mg every four weeks (q4w) regardless of body weight, or wherein the medicine, composition or product is manufactured to be useful for administering the antibody or antigen-binding fragment thereof to the individual at an initial loading dose of about 300 mg, and one or more maintenance doses of about 300 mg every four weeks (q4w), wherein a first maintenance dose is to be administered to the individual two weeks after the initial loading dose.
6. Use according to claim 5(a), characterized in that the medicine, composition or product is manufactured to be useful for administering the antibody or antigen-binding fragment to the individual as an initial dose followed by one or more secondary doses, optionally wherein the initial dose is about 100 mg and each secondary dose is about 100 mg, or wherein the individual has asthma with an eosinophilic phenotype that includes a baseline blood eosinophil count greater than or equal to 300 cells^L, or wherein the individual has asthma with a Type 2 inflammatory phenotype that includes one or both baseline blood eosinophil counts greater than or equal to 150 cells^L and a baseline FeNO greater than or equal to 20 ppb.
7. Use, according to claim 5(b), characterized in that the individual has uncontrolled moderate to severe asthma, or in that the individual has asthma with an eosinophilic phenotype that includes a baseline blood eosinophil count greater than or equal to 300 cells^L, or in that the individual has asthma with a Type 2 inflammatory phenotype that includes one or both baseline blood eosinophil counts greater than or equal to 150 cells^L and a baseline FeNO greater than or equal to 20 ppb.
8. Use, according to any one of claims 1 to 7, characterized in that the medicine, composition or product is manufactured to be useful for administering the antibody or antigen-binding fragment to the individual once every two weeks (q2w), optionally in which a first maintenance dose of the antibody or antigen-binding fragment is to be administered two weeks after an initial dose of the antibody or antigen-binding fragment, optionally in which maintenance doses of the antibody or antigen-binding fragment are to be administered for at least 24 weeks.
9. Use according to claim 5(c), characterized in that the individual aged between 6 years and less than 12 years has uncontrolled moderate to severe asthma or uncontrolled persistent asthma.
10. Use, according to any one of claims 1 to 9, characterized in that (i) the individual must receive a base therapy 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, cromoglycate sodium, a long-acting beta2 agonist and an antifungal agent or any combination thereof, or in which the individual must receive a base therapy comprising an inhaled corticosteroid (ICS) optionally in combination with a second controller medication, wherein optionally the second controller medication is selected from the group consisting of a long-acting β2 agonist (LABA), a leukotriene receptor antagonist (LTRA), a long-acting muscarinic antagonist (LAMA) and a methylxanthine, or in which the ICS is to be administered at a high dose or at a medium dose; and/or (ii) the antibody or antigen-binding fragment comprises a heavy chain variable region (HCVR) sequence of SEQ ID NO: 1 and a light chain variable region (LCVR) sequence of SEQ ID NO: 2, optionally wherein the antibody is dupilumab.
11. Composition or medicament, characterized in that it comprises an antibody or antigen-binding fragment that binds specifically to the interleukin-4 receptor (IL-4R), for use as defined in any of claims 1 to 10.
12. Pen-type administration device or autoinjector for subcutaneous administration, or standard syringe and needle for subcutaneous or intravenous administration, characterized in that it comprises an antibody or antigen-binding fragment thereof that binds specifically to the interleukin-4 receptor (IL-4R), for use as defined in any of claims 1 to 10.
13. Kit, characterized in that it comprises a pen-type administration device or an autoinjector for subcutaneous administration, or a standard syringe and needle for subcutaneous or intravenous administration, comprising an antibody or antigen-binding fragment thereof that binds specifically to the interleukin-4 receptor (IL-4R), for use as defined in any of claims 1 to 10, and optionally one or more medicinal components.
14. Use of an antibody or antigen-binding fragment thereof comprising three heavy chain CDR sequences comprising SEQ ID NOs: 3, 4 and 5, respectively, and three light chain CDR sequences comprising SEQ ID NOs: 6, 7 and 8, respectively, characterized in that it is in the manufacture of a drug, composition or product for treating asthma, wherein the antibody or antigen-binding fragment thereof binds specifically to the interleukin-4 receptor (IL-4R).

Description

SEQUENCE LISTING [0001] This application contains a Sequence Listing that was submitted electronically in ASCII format and is incorporated herein by reference in its entirety. Said ASCII copy, created on October 1, 2021, is named 721843_SA9-303PC_SL.txt and is 199,026 bytes in size. RELATED ORDERS [0002] This application claims priority to U.S. Provisional Patent Application Serial Numbers 63/087,668, filed October 5, 2020, 63/109,719, filed November 4, 2020, 63/144,048, filed February 1, 2021, and 63/157,922, filed March 8, 2021; and to European Patent Application No. 21315151.7, filed August 31, 2021. The full description of each of these applications is incorporated herein by reference in its entirety. FIELD OF THE INVENTION [0003] The present invention relates to the treatment and/or prevention of asthma in a pediatric patient who needs it. The invention relates to the administration of an interleukin-4 receptor antagonist (IL-4R) to treat or prevent asthma in a pediatric patient who needs it. BACKGROUND OF THE INVENTION [0004] Asthma is a chronic inflammatory disease of the airways characterized by hyperresponsiveness, acute and chronic bronchoconstriction, airway edema, and mucous plugging. The inflammatory component of asthma is believed to involve many cell types, including mast cells, eosinophils, T lymphocytes, neutrophils, epithelial cells, and their biological products. Patients with asthma typically present with symptoms of wheezing, shortness of breath, cough, and chest tightness. [0005] Most children with asthma have mild or moderate disease and can achieve adequate asthma control by avoiding triggers and/or with the aid of medications such as short-acting inhaled β2 agonists, inhaled corticosteroids (ICS), and, when necessary, the addition of long-acting β2 receptor agonists (LABA) and leukotriene receptor antagonists (LTRA). However, 2-5% of all asthmatic children have uncontrolled asthma despite maximal treatment with conventional medications. Children with such severe symptoms are heterogeneous with respect to triggers, lung function, inflammatory pattern, and clinical symptoms. These children have reduced quality of life, account for a large portion of asthma-related healthcare costs, and represent an ongoing clinical challenge for the pediatrician. [0006] The prolonged adverse effects of systemic and inhaled corticosteroids on bone metabolism, adrenal function, and growth in children have led to attempts to minimize the amount of corticosteroid use. Furthermore, the consequences of lack of response to therapy or lack of adherence to therapy are evidenced by loss of asthma control (LOAC), which can be severe (i.e., a severe asthma exacerbation event) and possibly fatal. [0007] Despite standard therapy, such as inhaled corticosteroids, children with uncontrolled moderate to severe asthma continue to experience symptoms such as coughing, wheezing, and shortness of breath, and are at risk of severe asthma attacks. Most children with asthma suffer from type 2 asthma, which often means frequent hospitalizations and emergency room visits. Uncontrolled asthma can cause children to miss school and can interfere with physical activity and routine tasks, including playing sports and climbing stairs. [0008] Furthermore, the pharmacokinetics of many medications differ in children compared to adults. The pharmacokinetic processes of absorption, distribution, metabolism, and excretion undergo changes due to growth and development. Therefore, finding the correct doses and regimens for children is complicated, and pediatric doses cannot always be directly extrapolated from adult studies while maintaining the necessary efficacy for treatment. [0009] Consequently, there is a need for new therapies to treat asthma in children. BRIEF SUMMARY OF THE INVENTION [0010] According to one aspect, a method is provided for treating asthma in an individual 6 years of age or older, wherein the individual has moderate to severe asthma with type 2 inflammation characterized by an eosinophilic phenotype and/or elevated fraction of exhaled nitric oxide (FeNO) or wherein the individual has oral corticosteroid-dependent asthma. The method involves administering to the individual an antibody or an antigen-binding fragment thereof that specifically binds to the interleukin-4 receptor (IL-4R), wherein the antibody or antigen-binding fragment thereof comprises three heavy-chain CDR sequences comprising SEQ ID NOs: 3, 4, and 5, respectively, and three light-chain CDR sequences comprising SEQ ID NOs: 6, 7, and 8, respectively. [0011] In certain exemplary embodiments, the antibody or antigen-binding fragment thereof is administered to the individual as an initial dose followed by one or more secondary doses. In certain exemplary embodiments, the initial dose is approximately 100 mg and each secondary dose is approximately 100 mg. In certain exemplary embodiments, the individual weighs from 15 kg to less than 30 kg. [0012] In certa