Altimmune begins Phase 3 PERFORMA trial of pemvidutide in MASH
Altimmune has initiated patient enrolment in PERFORMA, its global Phase 3 registrational trial of pemvidutide in metabolic dysfunction-associated steatohepatitis (MASH). The Gaithersburg, Maryland company said it moved from securing PERFORMA funding to first patient in under three months, a pace chief executive Jerry Durso described as evidence of the organisation's ability to "execute with speed and efficiency."
PERFORMA is a randomised, double-blind, placebo-controlled study targeting adults with MASH and confirmed moderate to advanced liver fibrosis (F2-F3). The design incorporates two parallel cohorts: Cohort 1 will enrol approximately 990 biopsy-confirmed patients and is structured to support an accelerated approval pathway based on MASH resolution and fibrosis improvement at 52 weeks; a second cohort of around 800 patients assessed via non-invasive tests will expand the safety dataset. Final regulatory approval in both cohorts is expected to hinge on liver-related clinical events at roughly 60 months. A 52-week interim readout is targeted for 2029.
Science and regulatory backdrop
Pemvidutide is a peptide designed to activate glucagon and GLP-1 receptors in a balanced 1:1 ratio. Glucagon receptor activation is intended to exert direct effects on the liver, reducing fat accumulation and inflammation, while GLP-1 receptor agonism drives appetite suppression, weight loss, and pathways linked to craving and reward. That dual mechanism underpins Altimmune's argument that pemvidutide may address both the hepatic and metabolic dimensions of MASH, as well as making the molecule relevant to alcohol use disorder (AUD) and alcohol-associated liver disease (ALD).
The trial design incorporates the FDA-qualified AIM-MASH AI Assist tool, which Altimmune says will help standardise histological assessment of liver biopsy samples, an area that has historically introduced variability into MASH trial outcomes. The FDA has granted pemvidutide both Fast Track and Breakthrough Therapy designations for MASH, the latter a relatively high bar that signals the agency sees meaningful potential over existing options. PERFORMA's design also reflects feedback from European regulatory agencies, suggesting the company intends the programme to serve as the basis for a simultaneous or closely sequenced European filing.
Chief medical officer Christophe Arbet-Engels cited the "favorable safety and tolerability" profile generated in the IMPACT Phase 2b study as the key foundation for advancing to Phase 3. In that earlier study, pemvidutide produced statistically significant MASH resolution rates, improvements in non-invasive fibrosis markers, and meaningful weight loss. Naim Alkhouri, chief medical officer at Summit Clinical Research and a PERFORMA principal investigator, noted that the critical question now is whether those improvements translate into meaningful outcomes at scale.
Competitive landscape
MASH has attracted intense pharmaceutical attention over the past three years. Madrigal Pharmaceuticals' resmetirom (Rezdiffra) became the first FDA-approved treatment for MASH with liver fibrosis in early 2024, establishing a commercial benchmark. Several other agents, including obeticholic acid derivatives and further GLP-1-based approaches from larger pharma players, are in late-stage or regulatory review. Altimmune's differentiation argument rests on the balanced glucagon/GLP-1 profile, which the company contends delivers more direct hepatic benefit than GLP-1-only approaches, though head-to-head data against approved agents do not yet exist.
Beyond MASH, Altimmune reported positive topline results from the RECLAIM Phase 2 trial in AUD in July 2026, and its RESTORE trial in alcohol-associated liver disease is enrolling, with completion expected in the third quarter of 2026. The breadth of the pemvidutide franchise across related liver and metabolic indications will be a factor investors and potential partners weigh as PERFORMA data accumulates toward its 2029 readout.