Pemvidutide Shows Continued Antifibrotic Activity for MASH, Progresses to Phase 3 Trial

Altimmune has announced positive topline results from the phase 2b IMPACT trial of pemvidutide, a balanced 1:1 glucagon/GLP-1 dual receptor agonist, in patients with metabolic dysfunction-associated steatohepatitis (MASH) at 48 weeks.1

As described in a December 19, 2025, press release from the Company, topline 48-week data showed treatment with pemvidutide achieved statistically significant improvements across treatment arms in key noninvasive tests (NITs), including Enhanced Liver Fibrosis (ELF) and Liver Stiffness Measurement (LSM), versus placebo. Of note, these data exhibited continued reductions from week 24 and provide evidence of continued improvement in antifibrotic activity with both treatment doses.1

“The magnitude of response versus placebo on measures such as ELF and LSM at 48 weeks makes these data particularly compelling, as these noninvasive markers have been shown to correlate with histologic fibrosis stage. These results reinforce that pemvidutide may address both liver-specific and metabolic drivers of MASH without compromising tolerability – three critical elements of a potential effective treatment for this patient population,” Mazen Noureddin, MD, IMPACT trial principal investigator, professor of medicine at Houston Methodist Hospital and co-chairman of the Board for Summit and Pinnacle Clinical Research, said in a statement.1 “I am encouraged by the dose response observed and the performance of the 1.8 mg arm and I am eager to see this differentiated therapeutic candidate advance into Phase 3 evaluation.”

Additionally, Altimmune announced that it held a productive End-of-Phase 2 meeting with the US Food and Drug Administration (FDA) resulting in alignment on the parameters for a registrational phase 3 trial of pemvidutide for MASH patients with moderate to advanced liver fibrosis.1

Pemvidutide is a novel, investigational peptide with balanced 1:1 glucagon/GLP-1 dual receptor agonist activity, in development for the treatment of MASH, alcohol use disorder (AUD) and alcohol-associated liver disease (ALD).1

The randomized, placebo-controlled, double-blind IMPACT trial enrolled 212 participants with biopsy-confirmed MASH and fibrosis stages F2 or F3, with and without diabetes. Study participants were randomly assigned in a 1:2:2 ratio to receive weekly subcutaneous pemvidutide doses at either 1.2 mg, 1.8 mg or placebo for 48 weeks.1

The primary efficacy endpoints, measured at 24 weeks, were MASH resolution without worsening of fibrosis, or fibrosis improvement without worsening of MASH. Secondary endpoints included non-invasive tests of fibrosis and weight loss measured at 24 and 48 weeks.1

Results showed pemvidutide-treated participants achieved statistically significant reductions in primary non-invasive markers of fibrosis, including ELF and LSM:

• ELF: 1.2 mg and 1.8 mg doses achieved a mean reduction from baseline of -0.49 and -0.58 respectively, versus +0.16 in placebo-treated patients (P <.0001, both doses)
• LSM: 1.2 mg and 1.8 mg doses achieved a mean reduction from baseline of -3.04 (P <.05) and -3.97 (P <.001), respectively, versus -0.03 in placebo-treated participants

The proportion of participants receiving pemvidutide 1.2 mg and 1.8 mg who achieved both a ≥0.5 reduction in ELF and a 30% reduction in LSM were 27.8% (P <.001) and 32.4% (P <.0001) respectively, versus 3.2% in placebo-treated participants.1

Further analysis revealed participants who received the pemvidutide 1.2 mg and 1.8 mg doses achieved a mean reduction in liver fat content from baseline of 45.2% and 54.7% respectively, compared to 8.2% in participants who received placebo (P <.0001). For ALT, 1.2 mg and 1.8 mg achieved a mean reduction from baseline of -37.8 IU/L and -37.4 IU/L respectively, versus -10.3 IU/L in placebo-treated participants (P <.0001, both doses). For cT1, 1.2 mg and 1.8 mg achieved a mean reduction from baseline of -124 and -140 milliseconds respectively, versus -21 milliseconds in placebo-treated participants (P <.0001, both doses).1

Results additionally showed participants receiving pemvidutide 1.2 mg and 1.8 mg achieved weight loss of 4.5% and 7.5%, respectively, compared with 0.2% of placebo-treated participants (P <.0001, both doses). Of note, no plateauing at 48 weeks was observed with the 1.8 mg dose.1

Adverse events leading to treatment discontinuation occurred in 0% and 1.2% of patients treated with pemvidutide 1.2 mg and 1.8 mg, respectively, versus 3.5% of participants on placebo. Investigators noted no serious or severe adverse events related to treatment were reported.1

Altimmune and the FDA have aligned on the parameters for a registrational phase 3 trial of pemvidutide for MASH patients with moderate to advanced liver fibrosis. With the FDA’s recent qualification of AIM-MASH AI Assist, the Agency was open to the Company’s intent to integrate use of this AI tool into the phase 3 trial.1,2

“With the benefit of FDA feedback and these 48-week data now in hand, we are greatly looking forward to progressing pemvidutide to a Phase 3 program which we intend to initiate in 2026. Strong evidence of antifibrotic improvements based upon non-invasive tests, combined with an attractive tolerability profile, highlight pemvidutide’s differentiation and potential to be a meaningful treatment option for the MASH patient community,” said Vipin Garg, PhD, Chief Executive Officer of Altimmune.1

References

1. Altimmune. Altimmune Announces that Pemvidutide Achieved Key Measures of Success at 48 Weeks in IMPACT Phase 2b MASH Trial. December 19, 2025. Accessed December 19, 2025. https://www.globenewswire.com/news-release/2025/12/19/3208385/0/en/Altimmune-Announces-that-Pemvidutide-Achieved-Key-Measures-of-Success-at-48-Weeks-in-IMPACT-Phase-2b-MASH-Trial.html

2. US Food and Drug Administration. FDA Qualifies First AI Drug Development Tool, Will Be Used in 'MASH' Clinical Trials. December 8, 2025. Accessed December 19, 2025. https://www.fda.gov/drugs/drug-safety-and-availability/fda-qualifies-first-ai-drug-development-tool-will-be-used-mash-clinical-trials