Once-weekly pemvidutide begins phase 3 trial for MASH

Altimmune has begun enrolling patients in a global phase 3 trial to assess pemvidutide in patients with metabolic dysfunction-associated steatohepatitis (MASH), a serious liver disease that causes the liver to swell and can lead to cirrhosis, liver cancer and liver failure. It is linked to Type 2 diabetes and other metabolic conditions such as obesity and affects about 7% of the global population.

Pemvidutide is an investigational glucagon/GLP-1 dual receptor agonist. Activating glucagon receptors results in direct effects on the liver, including reductions in liver fat, inflammation and fibrosis, while activating the GLP-1 receptor leads to appetite suppression and weight loss. Altimmune’s EuPort technology is able to prolong the half-life of pemvidutide, which allows for weekly dosing, animal studies find.

“With the balanced one-to-one glucagon/GLP-1 receptor agonism providing direct effects on the liver, as well as metabolic benefits, pemvidutide may offer an important new treatment option for patients with MASH and serious liver diseases,” Christophe Arbet-Engels, M.D., Ph.D., chief medical officer of Altimmune, said in a news release.

The PERFORMA trial is a global, randomized, double-blind, placebo-controlled study evaluating the efficacy, safety, and clinical outcomes of pemvidutide in MASH patients with moderate to advanced fibrosis. The trial will enroll almost 1,800 patients.

The study includes two cohorts; cohort 1 will enroll approximately 990 patients and is designed to support the accelerated approval pathway based on a biopsy-assessed primary efficacy endpoint of MASH resolution and/or fibrosis improvement at 52 weeks. A second cohort will enroll approximately 800 patients with fibrosis to add to the safety data.

The trial will integrate the AIM-MASH AI Assist tool to help standardize histological assessment of liver biopsy samples. Developed by PathAI, the tool was qualified by both the FDA and EMA for use within the context of clinical trials for MASH therapies and has been validated to be as accurate as pathologists in scoring liver biopsies.

In May 2026, the company reported data from the phase 2b IMPACT study. In this analysis, pemvidutide at 48 weeks reduced elevated lipids while improving multiple cardiometabolic risk factors in patients with MASH. The study demonstrated reductions in triglycerides by 23.7% and total cholesterol by 15.4%. Additionally, patients experienced a weight loss of 7% and improvements in blood pressure.

Previously, the company had reported IMPACT phase 2b trial results of pemvidutide on the Enhanced Liver Fibrosis (ELF), a blood test that is used to evaluate liver scarring severity, and the Liver Stiffness Measurement (LSM), an ultrasound test. In the trial, 27.8% of patients who received pemvidutide 1.2 mg and 32.4% for pemvidutide 1.8 mg achieved improvements in these endpoints compared with 3.2% of patients who received placebo.

Approximately 1% of patients receiving pemvidutide discontinued treatment due to adverse events (AEs), which the company said was lower than with placebo. The majority of adverse events were mild to moderate, and most gastrointestinal adverse events were mild to moderate in severity and generally occurred within the first eight weeks.

Pemvidutide also is in development for the treatment of alcohol use disorder (AUD) and alcohol-associated liver disease (ALD). In July 2026, the company announced topline results from the RECLAIM phase 2 trial in alcohol use disorder. In RECLAIM, pemvidutide 2.4 mg delivered a statistically significant and clinically meaningful reduction in heavy drinking days, the primary endpoint of the trial.

The RESTORE trial in alcohol-associated liver disease was initiated in July 2025, and enrollment completion is expected in the third quarter 2026.