The peer-reviewed journal, Hepatology Communications, has published a paper by Harrison et al. entitled, “Rencofilstat, a cyclophilin inhibitor: A phase 2a, multicenter, single-blind, placebo-controlled study in F2/F3 NASH,” reviewing the results of Hepion Pharmaceuticals’ (NASDAQ:HEPA) AMBITION clinical trial.
The Phase 2a, multicenter, single-blind, placebo-controlled study randomized 49 presumed F2/F3 NASH subjects to receive either 75 mg or 225 mg of rencofilstat, or placebo, once daily for 28 days. The aim of the study was to determine safety, tolerability, and pharmacokinetics, while exploring NASH efficacy biomarkers, including multi-omic and AI-POWR analyses.
As previously reported, the AMBITION clinical trial demonstrated rencofilstat was safe and well tolerated. A majority of subjects (28/47; 59.6%) who were dosed with rencofilstat, or placebo experienced no adverse events. Of the 36 adverse events recorded in total, 97.2% were graded as mild to moderate, none were serious, and the majority (27/36; 75%) were considered unrelated to administration of rencofilstat. In addition, blood concentrations of rencofilstat in the NASH subjects were similar to those observed previously in healthy subjects.
The reductions in alanine transaminase (ALT), a biomarker of liver damage, were greater in the rencofilstat arms, compared with the placebo groups and was statistically different in the 225-mg cohort, compared with the placebo cohort (-16.3 plus or minus 25.5% versus -0.7 plus or minus 13.4%, respectively).
Reductions in Pro-C3, a biomarker of collagen formation and fibrosis, and C6M, a biomarker of tissue remodeling, were statistically significant in rencofilstat subjects with baseline Pro-C3 levels above 15.0 ng/mL. Pro-C3 levels greater than 15-to-20 ng/mL are generally accepted to represent active NASH disease and a marker of fibrosis in the primary patient population for treatment by many NASH drug candidates.
The paper concluded that the reductions in ALT, Pro-C3, and C6M suggest that rencofilstat has direct antifibrotic effects with longer treatment duration, supporting the advancement of rencofilstat into a larger and longer Phase 2b study.
“The findings of this paper further strengthen the rationale behind our ongoing Phase 2b ASCEND-NASH trial, which initiated screening at the end of August,” Robert Foster, PharmD, Ph.D. and CEO of Hepion, said in a statement.
“The degree of decline in Pro-C3 observed in the AMBITION trial, which had a duration of only 28 days, was comparable to Pro-C3 declines seen in similar studies with durations of several months, particularly in subjects with Pro-C3 levels indicating more advanced disease,” he added.
“Given this observation, we are very much looking forward to seeing the magnitude of rencofilstat’s antifibrotic effects over a 12-month-period in our ongoing Phase 2b trial,” Dr. Foster said
The article may be accessed at: https://doi.org/10.1002/hep4.2100.
