Pemvidutide Gets Breakthrough Therapy Designation for MASH

The United States (US) Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) for pemvidutide for the treatment of metabolic dysfunction-associated steatohepatitis (MASH).1

“The FDA’s Breakthrough Therapy Designation for pemvidutide in MASH reinforces the promise of its clinical profile and potential to address significant unmet needs in this serious, progressive liver disease,” Jerry Durso, President and Chief Executive Officer of Altimmune, said in a statement1. “As I step into the CEO role, this designation represents an important validation for pemvidutide. Phase 2b data support its differentiated profile and the meaningful role it could play in MASH, and potentially other serious liver diseases. With this breakthrough designation and alignment with the FDA on registrational Phase 3 trial parameters, we are laser-focused on strengthening the foundation of Altimmune to advance pemvidutide through late-stage development – guided by our commitment to serve patients and create value for our stakeholders.”

Pemvidutide is a balanced 1:1 glucagon/GLP-1 dual receptor agonist. The FDA granted BTD to the therapy based on 24-week data from the IMPACT Phase 2b trial that demonstrated statistically significant MASH resolution without worsening of fibrosis and early and substantial improvements in liver fat and non-invasive tests (NITs) of fibrosis and hepatic inflammation.

More recently, 48-week data reported by Altimmune in December 2025 demonstrated that treatment with pemvidutide achieved statistically significant improvements across treatment arms in key 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.2

Impact enrolled 212 participants with biopsy-confirmed MASH and fibrosis stages F2 or F3, with or without diabetes. Participants were randomized in a 1:2:2 ratio to receive weekly subcutaneous pemvidutide at doses of 1.2 mg or 1.8 mg, or placebo, for 48 weeks. The primary efficacy endpoints, assessed at 24 weeks, were MASH resolution without worsening of fibrosis or improvement in fibrosis without worsening of MASH, while secondary endpoints included noninvasive tests of fibrosis and weight loss evaluated at both 24 and 48 weeks.2

At 24 weeks, pemvidutide treatment resulted in statistically significant improvements in key noninvasive markers of fibrosis. Mean ELF score reductions from baseline were −0.49 with the 1.2 mg dose and −0.58 with the 1.8 mg dose, compared with a mean increase of +0.16 in the placebo group (P < .0001 for both doses). Mean liver stiffness measurement (LSM) decreased by −3.04 with 1.2 mg (P < .05) and −3.97 with 1.8 mg (P < .001), versus −0.03 with placebo. A composite response of both a ≥0.5 reduction in ELF and a ≥30% reduction in LSM was achieved by 27.8% of participants receiving 1.2 mg and 32.4% receiving 1.8 mg, compared with 3.2% of placebo-treated participants (P < .001 and P < .0001, respectively).2

Additional analyses showed substantial metabolic and hepatic improvements with pemvidutide. Mean liver fat content was reduced by 45.2% with 1.2 mg and 54.7% with 1.8 mg, compared with 8.2% with placebo (P < .0001). Mean ALT decreased by −37.8 IU/L and −37.4 IU/L with the 1.2 mg and 1.8 mg doses, respectively, versus −10.3 IU/L with placebo (P < .0001 for both), while cT1 was reduced by −124 ms and −140 ms versus −21 ms (P < .0001). Weight loss reached 4.5% and 7.5% with pemvidutide 1.2 mg and 1.8 mg, respectively, compared with 0.2% with placebo (P < .0001), with no plateau observed at 48 weeks for the 1.8 mg dose. Adverse events leading to treatment discontinuation occurred in 0% and 1.2% of patients receiving pemvidutide 1.2 mg and 1.8 mg, respectively, compared with 3.5% in the placebo group, and no serious or severe treatment-related adverse events were reported.2

Altimmune has aligned with the FDA on the parameters for a planned registrational phase 3 trial of pemvidutide for MASH patients with moderate to advanced liver fibrosis evaluating multiple pemvidutide doses over a 52-week treatment period and incorporating biopsy-based endpoints to support a potential accelerated approval and the use of AIM-MASH AI Assist, the first AI pathology tool qualified by the FDA for use in MASH clinical trials.

References

1. Altimmune Receives FDA Breakthrough Therapy Designation for Pemvidutide in MASH. News release. Altimmune. January 5, 2026. https://www.globenewswire.com/news-release/2026/01/05/3212638/0/en/Altimmune-Receives-FDA-Breakthrough-Therapy-Designation-for-Pemvidutide-in-MASH.html

2. 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