Summary: In the phase 2b IMPACT trial in patients with F2–F3 MASH, 24 weeks of weekly pemvidutide met one primary endpoint, MASH resolution without fibrosis worsening (52–58% vs 20% placebo), but missed the other, fibrosis improvement, which did not significantly exceed placebo at this timepoint.
PICO Summary
| Element | Detail |
|---|---|
| Population | 212 patients with biopsy-confirmed MASH and fibrosis stage F2 or F3 (83 sites, USA and Australia; IMPACT trial). |
| Intervention | Once-weekly subcutaneous pemvidutide (GLP-1/glucagon dual agonist) 1.2 mg or 1.8 mg, no dose titration, for 24 weeks. |
| Comparison | Placebo once weekly (1:2:2 randomisation). |
| Outcome | MASH resolution without fibrosis worsening: 58% (1.2 mg; difference 38%, 95% CI 21–56; p<0.0001) and 52% (1.8 mg; difference 32%, 95% CI 19–46; p<0.0001) vs 20% placebo. Fibrosis improvement without MASH worsening: 33% (p=0.59) and 36% (p=0.27) vs 28%, not significant. Discontinuations for adverse events 0–1% vs 2%; most events mild-moderate. |
Weekly pemvidutide in F2–F3 MASH (IMPACT)
Phase 2b RCT · F2–F3 MASH · 24 weeks
Weekly pemvidutide more than doubled MASH resolution without worsening fibrosis (52% vs 20%; 58% at 1.2 mg), but did not improve fibrosis versus placebo at 24 weeks.
Expert Commentary
MASH is a field crying out for options beyond resmetirom, so a dual GLP-1/glucagon agonist showing a large, highly significant effect on MASH resolution, more than doubling the placebo rate, is a genuinely encouraging signal, and the tolerability with almost no discontinuations is a real plus. Honesty requires equal weight on the endpoint it missed, though: fibrosis improvement did not significantly beat placebo at 24 weeks. I read that as expected rather than damning, since fibrosis regression typically needs 48 weeks or more and resolution usually precedes it, but it remains an unmet co-primary, and the full 48-week data will be the real test. This is also phase 2b, 212 patients, with a deliberately small placebo arm. Can I use this with my patients? Not yet, pemvidutide is investigational, so for now it means counselling MASH patients that effective incretin-based options are advancing and considering trial enrolment where available. I would want the 48-week fibrosis results and phase 3 confirmation before this changes management, but the direction is promising.
References
Noureddin M, Harrison SA, Loomba R, et al. Safety and efficacy of weekly pemvidutide versus placebo for metabolic dysfunction-associated steatohepatitis (IMPACT): 24-week results from a multicentre, randomised, double-blind, phase 2b study. Lancet. 2025;406(10520):2644–2655. doi:10.1016/S0140-6736(25)02114-2