Safety and efficacy of weekly pemvidutide versus placebo for metabolic dysfunction-associated steatohepatitis (IMPACT): 48-week results from a multicentre, randomised, double-blind, phase 2b study
Noureddin M, Alkhouri N, Loomba R, et al. (2026). The Lancet Gastroenterology & Hepatology.
Summary
A 48-week randomised, double-blind, placebo-controlled phase 2b trial (IMPACT, NCT05989711) of weekly pemvidutide, a glucagon and GLP-1 receptor dual agonist, in 212 adults with biopsy-confirmed MASH and fibrosis stage F2 or F3. Participants at 83 sites in the United States and Australia were assigned to pemvidutide 1.2 mg (41 people), pemvidutide 1.8 mg (85) or placebo (86). The primary endpoints, MASH resolution without worsening of fibrosis and at least one stage of fibrosis improvement without worsening of MASH, were assessed on liver biopsy at 24 weeks. No biopsy was taken at week 48, so this paper reports secondary non-invasive measures only. Least-squares mean liver fat changed by -45.2% on 1.2 mg and -54.7% on 1.8 mg, against -8.2% on placebo. The 1.8 mg difference from placebo was -46.5 percentage points (95% confidence interval -57.7 to -35.3). Corrected T1 changed by -124.2 ms on 1.2 mg and -139.5 ms on 1.8 mg, against -20.5 ms. Alanine aminotransferase changed by -37.8 IU/L on 1.2 mg and -37.4 IU/L on 1.8 mg, against -10.3 IU/L. The enhanced liver fibrosis score changed by -0.49 on 1.2 mg and -0.58 on 1.8 mg, against +0.16 on placebo. The authors report each of these differences from placebo as statistically significant (p<0.0001). Nausea was the most common adverse event in that comparison: 9 of 41 people (22%) on 1.2 mg, 35 of 85 (41%) on 1.8 mg, and 15 of 86 (17%) on placebo. Treatment stopped because of an adverse event in none of the 1.2 mg group, 1 of 85 (1%) on 1.8 mg, and 3 of 86 (3%) on placebo. No severe or serious adverse event was defined as related to the study medication. The authors say the non-invasive results warrant a phase 3 trial. Altimmune funded the trial, and several authors are company employees. The company's 12 November 2026 announcement says the PERFORMA phase 3 trial is underway; that is the company's statement, not a finding in the abstract. Published online on 11 November 2026. Pemvidutide is investigational and not an approved medicine.