NGM Bio adds to woes in the search for a NASH treatment

Shares of US biotech NGM Biopharmaceuticals (Nasdaq: NGM) closed down more than 40% at $16.81 yesterday, after it revealed a major disappointment with its aldafermin in the treatment of non-alcoholic steatohepatitis (NASH), joining a string of failures in this therapy area.

NGM reported results from the 24-week Phase IIb ALPINE 2/3 study evaluating aldafermin in 171 patients with biopsy-confirmed NASH with stage 2 or 3 liver fibrosis (F2/F3). 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 3mg dose) and multiple non-invasive measures of NASH, including liver fat content reduction by MRI-PDFF, ALT, AST and Pro-C3 (at the 1mg and 3mg doses).

This is in strong contrast to the preliminary Phase II results reported early last year, when aldafermin was seen to be the first drug to demonstrate a robust, statistically-significant effect of greater than 20% of patients achieving the Food and Drug Administration composite regulatory endpoint of fibrosis improvement and resolution of NASH versus placebo, as well as show an impressive impact on both of these endpoints independently.