Hepion Pharmaceuticals Inc (NASDAQ: HEPA) is a clinical-stage biopharma company that focuses on developing therapeutic medications that can help treat liver diseases caused by non-alcoholic steatohepatitis. The company recently announced that they received positive topline results from the ‘Ambition’ NASH trial. In addition, they said that they met all the primary endpoints.
AMBITION NASH was a randomized Phase 2a, single-blind, placebo-controlled, multi-center trial designed to monitor the oral administration of 225 mg and 75 mg of CRV431 to the presumed subjects of F2 and F3 NASH for twenty-eight days. This was then to be followed by safety protocols that dictated they have an extra two-week observation period.
AMBITION’s primary outcome measure was the incidence of both tolerability and safety of the CRV431 drug versus placebo. The CRV431 drug at both doses was considered well-tolerated. There were no severe adverse events recorded. The few adverse events that were seen were unrelated to the drug and mostly mild.
In this trial, after the oral administration of either the 225 mg or 75 mg once daily doses, CRV431 blood concentration reached the effective range predicted for NASH treatment. In addition, it took only two hours for the study drug to reach maximum concentrations and roughly thirty minutes for an effective half-life. This all helped support once-daily dosing of the drug.
Recent reports have claimed that you can use serum alanine aminotransferase reductions as surrogate measures for NASH’s histologic improvement. The AMBITION clinical trial didn’t include any liver biopsies, but early efficacy indications were seen with both dosing cohorts and were disguised as ALT reductions. The ALT change that occurred from baseline to the 28th day displayed a CRV431 vs. placebo dose-to-response numerically. These declines were significant from placebo when both CRV431 doses were pooled.
AUC, or area-under-the-ALT-curve, for ALT changes, was calculated. The CRV431 study drug showed reduced ALT AUCs with larger doses, which helped indicate the positive dose-response.