Gannex Pharma Co. Ltd. announced the completion of the U.S. Phase I trial of ASC43F, an in-house developed, first-in-class dual targeting fixed-dose combination (FDC) tablet for non-alcoholic steatohepatitis (NASH). ASC43F is a once-a-day (QD), single tablet, FDC of 5 mg ASC41, a thyroid hormone receptor beta (THRß) agonist, and 15 mg ASC42, a farnesoid X receptor (FXR) agonist. The U.S. Phase I trial (ClinicalTrials.gov [1]
Identifier: NCT05118516) was an open-label, single-dose study evaluating the safety, tolerability and pharmacokinetics of ASC43F in healthy subjects. The results showed that ASC43F was safe and well tolerated, without clinically significant adverse effects. The pharmacokinetic parameters of ASC41 and ASC42 from ASC43F are similar to those of ASC41 and ASC42 as monotherapy. Previous Phase I studies in the U.S. and China have shown ASC41 at 5 mg to be safe and well tolerated in both healthy volunteers, overweight and obese subjects and patients with non-alcoholic fatty liver disease (NAFLD). In these studies, ASC41 significantly reduced low density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) in overweight and obese subjects with elevated LDL-C, a population that is characteristics of NASH. Previous Phase I clinical data indicated that ASC42 was safe and well tolerated, with no pruritus and with LDC-C values remaining within normal range during 14-day treatment with once-daily therapeutic dose of 15 mg. FXR target engagement biomarkers Fibroblast Growth Factor 19 (FGF19) increased 1,780% and 7a-hydroxy-4-cholesten-3-one (C4) decreased 91% on Day 14 of treatment with 15 mg, once-daily dose.