NGM's shares drop after mid-stage trial miss for aldafermin in NASH

Shares in NGM Biopharmaceuticals nearly halved on Monday after the company said that it will halt development of aldafermin in certain patients with non-alcoholic steatohepatitis (NASH) following the failure of a Phase IIb study. "These results are certainly disappointing," remarked CEO David Woodhouse, adding "the lack of significant fibrosis improvement was unexpected given the consistency of histology findings previously seen with aldafermin."

The ALPINE 2/3 trial randomised 171 patients with biopsy-confirmed NASH with F2-F3 liver fibrosis to receive once-daily subcutaneous injections of aldafermin at one of three doses or placebo. The study's primary objective was to evaluate a dose-response showing fibrosis improvement >1 stage with no worsening of NASH at week 24, while secondary goals included NASH resolution with no worsening of fibrosis, as well as fibrosis improvement and NASH resolution.

No dose-related response

Top-line results showed that 31% of patients who received aldafermin at a dose of 0.3 mg achieved the main goal, while in the 1-mg and 3-mg dose groups, the rates were 15% and 30% respectively, versus 19% for placebo. NGM noted that the study did achieve statistical significance on certain secondary endpoints, including NASH resolution with no worsening of fibrosis at the 3-mg dose, where the rate was 22% versus 6% for placebo.

Woodhouse added "in line with the data from [an earlier] study, ALPINE 2/3 achieved statistical significance on multiple non-invasive measures of NASH at the two higher doses." However, the executive said "given the failure to meet the primary endpoint, we have decided to shift resources that had previously been reserved for a Phase III F2/F3 NASH development programme toward advancing our other programmes."

Meanwhile, chief medical officer Hsiao Lieu noted "we plan to continue enrolment in our ongoing 48-week Phase IIb ALPINE 4 study to understand the profile of aldafermin in patients with F4 NASH and compensated cirrhosis." The experimental drug is an engineered analogue of the human hormone FGF19.

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