NGM Bio reports topline results from 24-week phase IIb ALPINE 2/3 study of aldafermin in NASH.

The trial was an equally randomized, double-blind, placebo-controlled study that assessed the efficacy, safety and tolerability of 0.3 mg, 1 mg and 3 mg doses of aldafermin once-daily subcutaneous injections compared to placebo. The study did not meet its primary endpoint evaluating a dose response showing improvement in liver fibrosis by >1 stage with no worsening of NASH at week 24 (p=0.55), analyzed using a dose response-driven statistical analysis plan (Multiple Comparison Procedure Modeling, or MCP-Mod). The study did achieve statistical significance versus placebo on certain secondary endpoints, including NASH resolution (at the 3 mg dose) and multiple non-invasive measures of NASH, including liver fat content reduction by MRI-PDFF, ALT, AST and Pro-C3 (at the 1 mg and 3 mg doses). "The lack of significant fibrosis improvement was unexpected given the consistency of histology findings previously seen with aldafermin in our adaptive four-cohort Phase II study,” said David J. Woodhouse, Ph.D., Chief Executive Officer at NGM. “However, in line with the data from that study, ALPINE 2/3 achieved statistical significance on multiple non-invasive measures of NASH at the two higher doses. That said, given the failure to meet the primary endpoint, we have decided to shift resources that had previously been reserved for a Phase 3 F2/F3 NASH development program toward advancing our other programs.”