New findings from the IMPACT trial suggest that the GLP-1–glucagon dual receptor agonist, pemvidutide, shows promise in treating metabolic dysfunction-associated steatohepatitis (MASH), a condition with a high global prevalence and limited therapeutic options.¹˒²
Pemvidutide is a dual receptor agonist that targets both the glucagon-like peptide-1 (GLP-1) and glucagon receptors, which are involved in metabolic regulation.
The IMPACT trial is an ongoing 48-week, international, phase 2b, randomised, double-blind, placebo-controlled study.² It enrolled 212 patients from 83 sites in the USA and Australia with biopsy-confirmed MASH and liver fibrosis stage F2 or F3. Participants were randomly assigned (1:2:2) to receive once-weekly subcutaneous injections of placebo, pemvidutide 1.2 mg, or pemvidutide 1.8 mg, administered without dose titration.
The dual primary endpoints for this 24-week analysis were MASH resolution without worsening of fibrosis, or at least a one-stage improvement in liver fibrosis without worsening of MASH.
The trial met its first primary endpoint. MASH resolution without worsening of fibrosis was achieved by 58% of patients in the 1.2 mg pemvidutide group (p<0.0001) and 52% in the 1.8 mg group (p<0.0001), compared to 20% in the placebo group.²
The second primary endpoint was not met at this timepoint. An improvement in fibrosis without worsening MASH was observed in 33% of the 1.2 mg group (p=0.59) and 36% of the 1.8 mg group (p=0.27), compared to 28% of the placebo group. These differences were not statistically significant.
Pemvidutide was reported to be well tolerated. Adverse events occurred in 78% of the 1.2 mg group, 81% of the 1.8 mg group, and 67% of the placebo group, with the majority being mild or moderate. Discontinuations due to adverse events were low: 0% in the 1.2 mg group, 1% in the 1.8 mg group, and 2% in the placebo group.
According to the study authors, “Pemvidutide treatment met the primary endpoint of MASH resolution without worsening of fibrosis at 24 weeks but did not meet the other primary endpoint of fibrosis improvement without worsening of MASH at this timepoint.”²
The IMPACT trial is ongoing to its 48-week conclusion, and the authors note that additional trials of longer duration are planned to further evaluate the effects of pemvidutide.
This study was funded by Altimmune.
References
1. Ho GJK, Tan FXN, Sasikumar NA, et al. High global prevalence of steatotic liver disease and associated subtypes: a meta-analysis. Clin Gastroenterol Hepatol. 2025; published online May 5. https://doi.org/10.1016/j.cgh.2025.02.006
2. 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; published online Nov 11. https://doi.org/10.1016/S0140-6736(25)02114-2
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