TOPLINE:

Pemvidutide, an investigational drug that is a dual agonist for GLP-1 and glucagon receptors, significantly improved fibrosis in adults with metabolic dysfunction-associated steatohepatitis (MASH) and stage F2 or F3 fibrosis, as determined by an artificial intelligence (AI) research algorithm in a phase 2 clinical trial.

METHODOLOGY:

• The IMPACT study included 212 adults with MASH and F2 or F3 fibrosis randomly assigned to once-weekly subcutaneous pemvidutide at doses of 1.2 mg (n = 41), 1.8 mg (n = 85), or placebo (n = 86).
• Patients’ biopsies were assessed by conventional pathology and further quantified by Liver Explore, a research algorithm not for diagnosis.
• Patients with missing biopsy data or those who discontinued treatment early were considered nonresponders.
• The primary outcome was the change in the proportion of the biopsy sample with pathologic liver fibrosis from baseline to week 24.

TAKEAWAY:

• The change from baseline in the area of pathologic fibrosis was significantly greater with both the 1.2-mg and 1.8-mg doses than with placebo, with absolute changes of -0.40% (P = .039) for 1.2 mg vs placebo, -0.69% (P < .001) for 1.8 mg vs placebo, and +0.38% for placebo.
• In a further analysis, 24% of the 1.2-mg group and 34% of the 1.8-mg group achieved a 60% relative decrease in early fibrosis compared with the placebo group.
• About 27% of patients in the 1.8-mg group had a 60% relative reduction in advanced fibrosis compared with 11% of patients in the placebo group.

IN PRACTICE:

“Pemvidutide significantly reduced the AI-quantified total fibrosis burden at 24 weeks, with effects in the early and advanced fibrosis compartments. Future studies should evaluate the relationship of continuous fibrosis improvement to outcomes,” the study authors concluded.

SOURCE:

The study was presented by Julio Gutierrez, MD, Scripps Health, San Diego, at The Liver Meeting 2025: American Association for the Study of Liver Diseases (AASLD).

LIMITATIONS:

The findings were limited by the small study population.

DISCLOSURES:

The study was funded by Altimmune. Gutierrez disclosed serving as a consultant for multiple companies including Altimmune.