NGM hunts for light at end of tunnel as midphase NASH trial hits primary goal

If at first you don’t succeed, try again. That’s what NGM Biopharma has done with a previously failed nonalcoholic steatohepatitis candidate in hopes that it could provide some light at the end of a dark time in the clinic.

The biotech announced Thursday in a first-quarter earnings report that aldafermin cleared the main goal of a phase 2b study called ALPINE 4 in 160 patients with the liver disease who had compensated cirrhosis. The disease has long troubled even the biggest pharmas, so a win could mean big things—especially for a biotech like NGM that has been struggling with other pipeline assets.

Aldafermin reduced enhanced liver fibrosis over the 48-week study when compared to placebo, meeting the main goal of the trial. On a secondary endpoint monitoring improvement in liver fibrosis stage, the 1-mg dose had a 21% change and the 3-mg dose had a 23% change, compared to 15% with placebo. These results were not statistically significant, with p-values of 0.39 and 0.36 for the 1-mg and 3-mg doses, respectively. NGM noted that the trial was not powered for this endpoint.

Aldafermin previously failed a phase 2b study called ALPINE 2/3 that was based on fibrosis stage improvement. 

On safety, NGM reported that aldafermin was generally well tolerated with no treatment-related serious adverse events. The safety and tolerability profile was consistent with previous studies of the therapy, which showed a higher rate of gastrointestinal events in patients receiving the treatment than those who took placebo.

Even with the hit on the main endpoint, NGM indicated that aldafermin will not advance without some help. “We look forward to having conversations with potential partners to determine further development of the program,” Chief Medical Officer Hsiao Lieu, M.D., said in the release.

NGM reported cash and equivalents of $231 million as of March 31, compared to $271.5 million on Dec. 31, 2022. The company is also seeing revenue from a partnership with Merck & Co. decline as that company narrows a major collaboration originally signed in 2015. NGM said that revenue from the Merck partnership was $2.2 million for the first quarter of 2023 compared to $20.9 million for the same period a year earlier. That revenue decline is expected to continue this year, according to the release.

Last month, NGM moved to reduce its head count by 33% after the midphase failure of Merck-partnered eye disease candidate NGM621 in October 2022. That restructuring is expected to be mostly complete by the end of this quarter, NGM said in the earnings release. NGM is reallocating resources toward its solid tumor oncology portfolio and drug discovery efforts.