COMPOSITIONS AND METHODS TO TREAT NON-ALCOHOLIC FATTY LIVER DISEASES (NAFLD)
Provided herein are methods and combination therapies useful for the treatment of non-alcoholic fatty liver diseases (NAFLD). In particular, provided herein are methods and combination therapies for treating NAFLD by administering a combination therapy comprising (a) the compound of Formula (I), or a pharmaceutically acceptable salt thereof, and (b) an additional therapeutic agent, or a pharmaceutically acceptable salt thereof. Also provided are pharmaceutical compositions and pharmaceutical combinations comprising the compound of Formula (I), or a pharmaceutically acceptable salt thereof, and an additional therapeutic agent, or a pharmaceutically acceptable salt thereof.
1 - 75 . (canceled)
76 . A method of treating non-alcoholic fatty liver disease (NAFLD) in a subject in need thereof comprising administering to the subject
(a) the compound of Formula (I),
or a pharmaceutically acceptable salt or solvate thereof, and
(b) a compound selected from the group consisting of an ASK1 inhibitor, an ACC inhibitor, a caspase inhibitor, a MCR antagonist, a statin, a PCSK9 inhibitor, or a pharmaceutically acceptable salt or solvate of any of the foregoing,
wherein the amounts of (a) and (b) together are effective in treating NAFLD.
77 . The method of claim 76 , wherein the NAFLD is nonalcoholic steatohepatitis (NASH).
78 . The method of claim 76 , wherein the NAFLD is NASH with attendant liver cirrhosis.
79 . The method of claim 77 , wherein the treatment of NASH decreases the level of serum bile acids in the subject.
80 . The method of claim 77 , wherein the treatment of NASH comprises treatment of pruritus.
81 . The method of claim 76 , wherein the NAFLD activity score (NAS) following administration is 7 or less; or is 5 or less; or is 3 or less.
82 . The method of claim 76 , wherein the compound is an ASK1 inhibitor selected from the group consisting of: selonsertib, MSC 2032964A, NQDI 1, TC ASK 10, AGI-1067, GS-444217, K811, K812, and SRT-015.
83 . The method of claim 76 , wherein the compound is an ACC inhibitor selected from the group consisting of:
84 . The method of claim 76 , wherein the compound is a caspase inhibitor selected from the group consisting of: emricasan,
85 . The method of claim 76 , wherein the compound is a MCR antagonist selected from the group consisting of: spironolactone, finerenone, eplerenone, canrenone, mexrenone, amlodipine, apararenone, benidipine, esaxerenone, felodipine, nefedipine, nimodipine, and nitrendipine.
86 . The method of claim 76 , wherein the compound is a statin selected from the group consisting of: atorvastatin, cerivastatin, fluvastatin, lovastatin, mevastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin.
87 . The method of claim 76 , wherein the compound is a PCSK9 inhibitor selected from the group consisting of: alirocumab, evolocumab, bococizumab, 1D05-IgG2, RG-7652, LY3015014, and inclisiran.
88 . A method of treating fibrosis in a subject in need thereof comprising administering to the subject
(a) the compound of Formula (I),
or a pharmaceutically acceptable salt or solvate thereof, and
(b) a compound selected from the group consisting of an ASK1 inhibitor, an ACC inhibitor, a caspase inhibitor, a MCR antagonist, a statin, a PCSK9 inhibitor, or a pharmaceutically acceptable salt or solvate of any of the foregoing,
wherein the amounts of (a) and (b) together are effective in treating NAFLD.
89 . The method of claim 88 , wherein the compound is an ASK1 inhibitor selected from the group consisting of: selonsertib, MSC 2032964A, NQDI 1, TC ASK 10, AGI-1067, GS-444217, K811, K812, and SRT-015.
90 . The method of claim 88 , wherein the compound is an ACC inhibitor selected from the group consisting of:
91 . The method of claim 88 , wherein the compound is a caspase inhibitor selected from the group consisting of: emricasan,
92 . The method of claim 88 , wherein the compound is a MCR antagonist selected from the group consisting of: spironolactone, finerenone, eplerenone, canrenone, mexrenone, amlodipine, apararenone, benidipine, esaxerenone, felodipine, nefedipine, nimodipine, and nitrendipine.
93 . The method of claim 88 , wherein the compound is a statin selected from the group consisting of: atorvastatin, cerivastatin, fluvastatin, lovastatin, mevastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin.
94 . The method of claim 88 , wherein the compound is a PCSK9 inhibitor selected from the group consisting of: alirocumab, evolocumab, bococizumab, 1D05-IgG2, RG-7652, LY3015014, and inclisiran.
95 . A pharmaceutical composition comprising
(a) the compound of Formula (I),
or a pharmaceutically acceptable salt or solvate thereof,
(b) a compound selected from the group consisting of an ASK1 inhibitor, an ACC inhibitor, a caspase inhibitor, a MCR antagonist, a statin, a PCSK9 inhibitor, or a pharmaceutically acceptable salt or solvate of any of the foregoing, and
one or more pharmaceutical excipients.