METHODS OF TREATING NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) USING IL-17RA ANTIBODY
The present disclosure is directed to a method of treating nonalcoholic fatty liver disease (NAFLD), and subsets thereof such as nonalcoholic steatohepatitis (NASH), using an IL-17 antagonist, such as a monoclonal antibody that specifically binds to IL-17 receptor A (IL-17RA).
1 . A method of treating nonalcoholic fatty liver disease (NAFLD) in a subject, which comprises administering to the subject a composition comprising a therapeutically effective amount of a monoclonal antibody that specifically binds to interleukin 17 receptor A (IL-17RA), or an antigen-binding fragment thereof, and a pharmaceutically acceptable carrier, whereby the NAFLD is treated in the subject.
2 . The method of claim 1 , wherein the subject suffers from nonalcoholic steatohepatitis (NASH).
3 . The method of claim 2 , wherein the subject suffers from noncirrhotic nonalcoholic steatohepatitis with liver fibrosis (NC-NASH+LF).
4 . A method of reducing liver inflammation in a subject in need thereof, which comprises administering to the subject a composition comprising a therapeutically effective amount of a monoclonal antibody that specifically binds to interleukin 17 receptor A (IL-17RA), or an antigen-binding fragment thereof, and a pharmaceutically acceptable carrier, whereby liver inflammation in the subject is reduced.
5 . The method of claim 4 , wherein the subject suffers from nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH).
6 . The method of any one of claims 1 - 5 , wherein the monoclonal antibody comprises:
(a) a heavy chain variable region comprising a complementarity determining region 1 (CDR) amino acid sequence of SEQ ID NO: 1, a CDR2 amino acid sequence of SEQ ID NO: 2, and a CDR3 amino acid sequence of SEQ ID NO: 3; and
(b) a light chain variable region comprising a complementarity determining region 1 (CDR) amino acid sequence of SEQ ID NO: 4, a CDR2 amino acid sequence of SEQ ID NO: 5, and a CDR3 amino acid sequence of SEQ ID NO: 6.
7 . The method of claim 6 , wherein the monoclonal antibody comprises a heavy chain variable region amino acid sequence of SEQ ID NO: 7 and a light chain variable region amino acid sequence of SEQ ID NO: 8.
8 . The method of any one of claims 1 - 7 , wherein the subject suffers from psoriasis.
9 . The method of any one of claims 1 - 8 , wherein the composition comprises about 150 mg to about 250 mg of the monoclonal antibody.
10 . The method of claim 9 , wherein the composition comprises about 210 mg of the monoclonal antibody.
11 . The method of any one of claims 1 - 10 , wherein the composition comprises about 210 mg of brodalumab formulated with about 10 mM L-glutamate, about 3% (w/v) L-proline, and about 0.001% (w/v) polysorbate 20, and the pH of the composition is about 4.8.
12 . The method of any one of claims 1 - 11 , wherein the composition is administered at least once a week in a therapeutic period.
13 . The method of claim 12 , wherein the composition is administered once a week for three weeks, followed by once every two weeks for 12 weeks in a therapeutic period of 15 weeks.
14 . The method of any one of claims 1 - 13 , wherein the method results in a decrease in the levels of liver enzymes and/or a decrease in the level of c-reactive protein (CRP) in the subject.
15 . The method of claim 14 , wherein the method results in a decrease in the levels of aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) in the subject.
16 . A monoclonal antibody that specifically binds to interleukin 17 receptor A (IL-17RA), or an antigen-binding fragment thereof, for use in treating nonalcoholic fatty liver disease (NAFLD) in a subject, wherein the antibody or antigen-binding fragment thereof is comprised in a composition comprising a pharmaceutically acceptable carrier, and wherein the antibody or antigen-binding fragment thereof is preferably administered to the subject in a therapeutically effective amount.
17 . The monoclonal antibody or antigen-binding fragment thereof for use according to claim 16 , wherein the subject suffers from nonalcoholic steatohepatitis (NASH).
18 . The monoclonal antibody or antigen-binding fragment thereof for use according to claim 17 , wherein the subject suffers from noncirrhotic nonalcoholic steatohepatitis with liver fibrosis (NC-NASH+LF).
19 . A monoclonal antibody that specifically binds to interleukin 17 receptor A (IL-17RA), or an antigen-binding fragment thereof, for use in reducing liver inflammation in a subject, wherein the antibody or antigen-binding fragment thereof is comprised in a composition comprising a pharmaceutically acceptable carrier, and wherein the antibody or antigen-binding fragment thereof is preferably administered to the subject in a therapeutically effective amount.
20 . The monoclonal antibody or antigen-binding fragment thereof for use according to claim 19 , wherein the subject suffers from nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH).
21 . The monoclonal antibody or antigen-binding fragment thereof for use according to any one of claims 16 to 20 , wherein the monoclonal antibody comprises:
(a) a heavy chain variable region comprising a complementarity determining region 1 (CDR) amino acid sequence of SEQ ID NO: 1, a CDR2 amino acid sequence of SEQ ID NO: 2, and a CDR3 amino acid sequence of SEQ ID NO: 3; and
(b) a light chain variable region comprising a complementarity determining region 1 (CDR) amino acid sequence of SEQ ID NO: 4, a CDR2 amino acid sequence of SEQ ID NO: 5, and a CDR3 amino acid sequence of SEQ ID NO: 6.
22 . The monoclonal antibody or antigen-binding fragment thereof for use according to claim 21 , wherein the monoclonal antibody comprises a heavy chain variable region amino acid sequence of SEQ ID NO: 7 and a light chain variable region amino acid sequence of SEQ ID NO: 8.
23 . The monoclonal antibody or antigen-binding fragment thereof for use according to any one of claims 16 to 22 , wherein the subject suffers from psoriasis.
24 . The monoclonal antibody or antigen-binding fragment thereof for use according to any one of claims 16 to 23 , wherein the composition comprises about 150 mg to about 250 mg of the monoclonal antibody.
25 . The monoclonal antibody or antigen-binding fragment thereof for use according to claim 24 , wherein the composition comprises about 210 mg of the monoclonal antibody.
26 . The monoclonal antibody or antigen-binding fragment thereof for use according to any one of claims 16 to 25 , wherein the composition comprises about 210 mg of brodalumab formulated with about 10 mM L-glutamate, about 3% (w/v) L-proline, and about 0.001% (w/v) polysorbate 20, and the pH of the composition is about 4.8.
27 . The monoclonal antibody or antigen-binding fragment thereof for use according to any one of claims 16 to 26 , wherein the composition is administered at least once a week in a therapeutic period.
28 . The monoclonal antibody or antigen-binding fragment thereof for use according to claim 27 , wherein the composition is administered once a week for three weeks, followed by once every two weeks for 12 weeks in a therapeutic period of 15 weeks.
29 . The monoclonal antibody or antigen-binding fragment thereof for use according to any one of claims 16 to 28 , wherein the use results in a decrease in the levels of liver enzymes and/or a decrease in the level of c-reactive protein (CRP) in the subject.
30 . The monoclonal antibody or antigen-binding fragment thereof for use according to claim 29 , wherein the use results in a decrease in the levels of aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) in the subject.