NGM Biopharmaceuticals, Inc. shared positive, comprehensive results from its Phase 2b ALPINE 4 trial of aldafermin, an engineered FGF19 analog product candidate, in patients with compensated cirrhosis (liver fibrosis stage 4 or F4) due to NASH in an oral plenary presentation at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting®?. The ALPINE 4 trial evaluated the efficacy, safety and tolerability of 1 mg and 3 mg doses of aldafermin compared to placebo in 160 patients with compensated cirrhosis (F4) due to NASH. (A 0.3 mg aldafermin cohort was part of the original design of the trial and enrolled seven patients prior to being discontinued in favor of enrolling more patients in the 1 mg and 3 mg arms of the trial.

Patients in the 0.3 mg arm were primarily evaluated for safety.) The study showed that the primary endpoint was achieved; patients treated with aldafermin 3 mg showed a statistically significant reduction in ELF score compared to the placebo arm after 48 weeks of treatment. ELF is the first and only FDA-approved non-invasive test reflecting NASH prognosis. ELF measures direct markers of liver fibrosis and can be used to predict liver-related events in patients with NASH and compensated cirrhosis.

Although ALPINE 4 was not statistically powered for the secondary endpoint of histological fibrosis improvement of = 1-stage (NASH Clinical Research Network, or CRN, criteria), a dose-dependent trend in fibrosis improvement was observed. Aldafermin demonstrated significant, dose-dependent improvements across all of the study?s non-invasive secondary endpoints, including neoepitope-specific N-terminal propeptide of type III collagen (Pro-C3), alanine aminotransferase (ALT), aspartate aminotransferase (AST), 7alpha-hydroxy-4-cholesten-3-one (C4), bile acids and liver stiffness measurement (LSM) by FibroScan® at week 48. These non-invasive tests are correlated with liver fibrogenesis, liver inflammation and injury, and NASH progression.

Aldafermin was generally well tolerated in the ALPINE 4 study with no treatment-related serious adverse events and a safety and tolerability profile generally consistent with prior trials of aldafermin, including higher levels of gastrointestinal events in patients treated with aldafermin as compared to patients treated with placebo. Aldafermin-associated increase in low-density lipoprotein cholesterol, consistent with on-target inhibition of bile acid synthesis, was mitigated by co-administration of rosuvastatin. There was no observed signal for adverse cardiovascular events in this trial related to aldafermin.