Pemvidutide Cuts Liver Fat Sharply in 48-Week MASH Trial

A weekly injection cut liver fat by more than half in a year-long trial whose full 48-week results were published November 12, 2026 in The Lancet Gastroenterology & Hepatology. The drug is pemvidutide, Altimmune's balanced 1:1 glucagon/GLP-1 dual receptor agonist, tested in the IMPACT Phase 2b trial in metabolic dysfunction-associated steatohepatitis, or MASH. At 48 weeks, liver fat content fell 45.2 percent on the 1.2 milligram dose and 54.7 percent on 1.8 milligrams. Placebo fell 8.2 percent. Both gaps were statistically significant at p less than 0.0001.

IMPACT enrolled 212 participants with biopsy-confirmed MASH and stage F2 or F3 fibrosis, with and without diabetes, randomized 1:2:2 to weekly subcutaneous pemvidutide at 1.2 milligrams (41 people), 1.8 milligrams (85 people) or placebo (86 people), with no dose titration. Screening was wide: 1,557 patients were screened between July 27, 2023 and November 21, 2025 to randomize those 212. The trial is registered as NCT05989711 and is complete.

The honest limit sits in the methods. Liver biopsies weren't collected at week 48, so the 48-week readout covers secondary endpoints measured non-invasively: imaging-based liver fat, blood markers of inflammation and fibrosis scores, and liver stiffness. The biopsy verdict came earlier. At 24 weeks, the trial met its primary endpoint, with MASH resolution without worsening of fibrosis in about 59 percent on 1.2 milligrams and 52 percent on 1.8 milligrams, against about 19 percent on placebo. The 48-week data say the non-invasive measures kept improving; they don't directly prove what a biopsy would show.

Responder analyses presented at The Liver Meeting 2026 in Denver sharpen the picture. In the most stringent composite, requiring concurrent improvement in liver fat, the ELF fibrosis score and liver stiffness, 25.8 percent of patients on the 1.8 milligram dose responded, against none on placebo. A broader composite put the figure at up to 42.9 percent against 3.3 percent. Composite non-invasive responses, though, haven't been validated as surrogate endpoints for approval, which is why they support a Phase 3 case rather than substitute for one.

That Phase 3 exists. Altimmune began enrolling PERFORMA in August 2026, planning roughly 990 patients in a biopsy-based cohort with a primary endpoint at 52 weeks and about 800 more in a cohort identified by non-invasive tests, with a 52-week readout expected in 2029. Pemvidutide holds FDA breakthrough therapy designation for MASH, granted in January 2026. The company reported generally favorable tolerability at 48 weeks with few discontinuations for adverse events.

MASH is the progressive form of fatty liver disease, and its treatment market is being built drug by drug, endpoint by endpoint. Pemvidutide's claim is a dual mechanism: GLP-1 for appetite and metabolic control, glucagon aimed directly at burning liver fat. The 48-week numbers keep that claim alive and quantified. What they can't do, and don't pretend to do, is finish the argument. The biopsy cohort in PERFORMA is where this drug's future gets decided.