Pemvidutide Shows Significant MASH Effects, Weight Loss at 24 Weeks in Phase 2b IMPACT Trial

Altimmune has announced positive topline results from the phase 2b IMPACT trial of pemvidutide in patients with metabolic dysfunction-associated steatohepatitis (MASH).1

According to a June 26, 2025, press release, the trial met its primary endpoint with statistically significant MASH resolution without worsening of fibrosis in up to 59.1% of participants and fibrosis improvement without worsening of MASH in up to 34.5% of participants in intent-to-treat (ITT) analyses as well as weight loss of up to 6.2% at 24 weeks with no plateauing. Of note, the data make pemvidutide the first product candidate to demonstrate significant MASH effects and weight loss at 24 weeks.1

“These data represent an important step forward in the development of pemvidutide for the treatment of MASH and reinforce our conviction in its potential to disrupt the treatment paradigm in this serious and rapidly growing disease,” Vipin Garg, PhD, President and Chief Executive Officer of Altimmune, said in a press release.1 “Despite a prevalence expected to exceed 27 million by 2030 in the United States alone, current treatment options are limited. We are excited to continue our efforts to bring this potentially transformative therapy to MASH patients.”

A novel, investigational, peptide-based 1:1 GLP-1/glucagon dual receptor agonist, pemvidutide is currently in development for the treatment of MASH, obesity, alcohol use disorder (AUD), and alcohol-associated liver disease (ALD). In clinical trials to date, once-weekly pemvidutide has demonstrated statistically significant MASH resolution and positive trends in liver fibrosis improvement, weight loss with class-leading lean mass preservation, and reductions in liver fat content, triglycerides, LDL cholesterol and blood pressure. The US Food and Drug Administration granted Fast Track designation to pemvidutide for the treatment of MASH in October 2023.1,2

Pemvidutide completed the MOMENTUM phase 2 obesity trial in 2024 and is being studied in the ongoing IMPACT phase 2b MASH trial, which enrolled 212 participants with biopsy-confirmed MASH and fibrosis stages F2/F3 with and without diabetes who were randomized in a 1:2:2 ratio to receive either weekly subcutaneous pemvidutide at 1.2 mg and 1.8 mg doses or placebo for 24 weeks. Key efficacy endpoints were MASH resolution without worsening of fibrosis, or fibrosis improvement without worsening of MASH at 24 weeks. Secondary endpoints included weight loss and non-invasive tests of fibrosis. Participants will receive a total of 48 weeks of treatment, with a final readout anticipated in the fourth quarter of 2025.1

In IMPACT, treatment discontinuation rates were low, with 9% of participants prematurely discontinuing treatment. In an ITT analysis, in which participants with missing biopsies were considered non-responders, the proportions of participants achieving MASH resolution without worsening of fibrosis at 24 weeks were 59.1% and 52.1% for pemvidutide 1.2 mg and 1.8 mg, respectively, versus 19.1% for placebo (P <.0001 both doses). The effects on fibrosis improvement without worsening of MASH in an ITT analysis were 31.8% and 34.5% for pemvidutide 1.2 mg and 1.8 mg, respectively, compared with 25.9% for placebo (differences not statistically significant).1

Additional supplemental AI-based analysis demonstrated statistically significant reductions in fibrosis, including 30.6% of participants receiving pemvidutide 1.8 mg achieving a ≥ 60% reduction in fibrosis compared to 8.2% receiving placebo (P <.001). Statistically significant changes in well-established non-invasive tests of fibrosis, including enhanced liver fibrosis score (ELF) and vibration-controlled transient elastography (VCTE), were also observed compared with placebo at both doses.1

At 24 weeks, mean weight loss in pemvidutide-treated participants was 5.0% and 6.2% at the 1.2 mg and 1.8 mg doses, respectively, versus 1.0% in the placebo arm (P <.001, both doses). Pemvidutide also demonstrated favorable safety and tolerability, with 0.0% and 1.2% adverse events related discontinuations in the pemvidutide 1.2 mg and 1.8 mg groups versus 2.4% in the placebo group, and there were no serious adverse events related to study medication.1

“The combination of MASH resolution and weight loss achieved at only 24 weeks is unique among drugs in development for MASH. The tolerability of pemvidutide was also impressive, with one of the lowest rates of AE-related drug discontinuations observed in any MASH clinical trial to date,” Mazen Noureddin, MD, MHSc, Professor of Medicine at the Houston Methodist Hospital and Co-Chairman of the Board for Summit and Pinnacle Clinical Research, commented.1 “The significant reduction in fibrosis in AI-based readings and its corroboration with established NITs suggest that pemvidutide has potent anti-fibrotic activity and that statistical significance on the fibrosis improvement endpoint could be achieved with longer durations of treatment.”

Investigational New Drug applications for pemvidutide in AUD and ALD have received FDA clearance, with a phase 2 trial in AUD underway and a phase 2 trial in ALD scheduled to commence in the third quarter of 2025.1

“Based on the results generated in the IMPACT trial, pemvidutide demonstrated significant MASH resolution and encouraging evidence of fibrosis improvement at 24 weeks. Additionally, when one considers the weight loss and favorable tolerability associated with pemvidutide, we believe that there is a clear path to a successful End of Phase 2 meeting with the FDA in the fourth quarter of 2025, enabling rapid progression to Phase 3,” Scott Harris, Chief Medical Officer of Altimmune, said in a statement.1

References

1. Altimmune. Altimmune Announces Positive Topline Results from the IMPACT Phase 2b Trial of Pemvidutide in the Treatment of MASH. June 26, 2025. Accessed June 26, 2025. https://ir.altimmune.com/news-releases/news-release-details/altimmune-announces-positive-topline-results-impact-phase-2b

2. Altimmune. Altimmune Granted Fast Track Designation by FDA for Pemvidutide for the Treatment of Non-Alcoholic Steatohepatitis (NASH). October 26, 2023. Accessed June 26, 2025. https://ir.altimmune.com/news-releases/news-release-details/altimmune-granted-fast-track-designation-fda-pemvidutide