Pemvidutide

Safety and Efficacy of Pemvidutide in Metabolic Dysfunction-Associated Steatohepatitis (MASH) — IMPACT Phase 2b

IMPACT is a multicentre, randomised, double-blind, placebo-controlled Phase 2b study evaluating once-weekly subcutaneous pemvidutide (1.2 mg or 1.8 mg) versus placebo for 24 weeks in adults with biopsy-confirmed MASH and fibrosis stages F2/F3. Primary 24-week results published in The Lancet (2025, PMID 41237796): MASH resolution without fibrosis worsening was achieved in 58% (1.2 mg) and 52% (1.8 mg) versus 20% with placebo (p<0.0001). Fibrosis improvement of ≥1 stage achieved in 34.5% (1.8 mg) vs placebo. The FDA granted Breakthrough Therapy Designation for pemvidutide in MASH in January 2026. New 48-week extension data presented at EASL 2026 (May 2026) showed sustained and significant reductions in triglycerides and total cholesterol, improvements in weight, waist circumference, and blood pressure. Altimmune plans to initiate Phase 3 registration trial in MASH in 2026.

A Phase 2 Study to Evaluate the Safety and Efficacy of ALT-801 (Pemvidutide) in Adults With Obesity or Overweight — MOMENTUM

MOMENTUM is a randomised, double-blind, placebo-controlled Phase 2b study evaluating once-weekly subcutaneous pemvidutide at 1.2 mg, 1.8 mg, and 2.4 mg versus placebo in adults with obesity or overweight over 48 weeks. Results presented at ADA 84th Scientific Sessions (2024): mean weight loss of 10.3%, 11.2%, and 15.6% at 1.2 mg, 1.8 mg, and 2.4 mg respectively versus 2.2% with placebo at week 48. Significant reductions in liver fat (up to 78.6% at high dose) and favourable lipid profile improvements observed. Altimmune completed end-of-Phase 2 meeting with FDA in 2026, advancing towards Phase 3 in obesity.

RECLAIM STUDY: A Phase 2 Evaluating the Efficacy and Safety of Pemvidutide in the Treatment of Alcohol Use Disorder (AUD) in Subjects With Obesity or Overweight

RECLAIM is a randomised, double-blind, placebo-controlled Phase 2 trial evaluating once-weekly subcutaneous pemvidutide 2.4 mg versus placebo for 24 weeks in approximately 100 adults with alcohol use disorder (AUD) and comorbid obesity or overweight (BMI >25 kg/m²), the first Phase 2 multicentre study of a dual glucagon/GLP-1 agonist in AUD to report results. Altimmune announced positive topline results July 28, 2026: the trial met its primary endpoint, change from baseline in heavy drinking days (HDD) per week at week 24, with pemvidutide reducing HDD by -4.20 (LS mean) versus -2.75 with placebo (treatment difference -1.45, p=0.0014). Key secondary endpoints (both FDA-recognized registrational endpoints) were also met: 2-level reduction in WHO Risk Drinking Levels (64.4% vs 34.8%, OR 3.31, p=0.0049) and zero heavy drinking days at weeks 21-24 (42.2% vs 17.4%, OR 3.84, p=0.0066). Percent days with abstinence increased 18.4 percentage points more than placebo (p=0.0075), and serum phosphatidylethanol (PEth), an objective alcohol-intake biomarker, fell significantly more with pemvidutide (p<0.0001). Bodyweight fell a placebo-adjusted 9.1% at 24 weeks (p<0.0001) with no plateau. Tolerability was generally favorable; most adverse events (nausea, vomiting, diarrhea, constipation) were mild-to-moderate. Altimmune plans to request an End-of-Phase 2 meeting with the FDA. The FDA has granted Fast Track Designation to pemvidutide for AUD.

RESTORE TRIAL: A Phase 2 Study Evaluating the Efficacy and Safety of Pemvidutide in the Treatment of Alcohol-Associated Liver Disease (ALD)

RESTORE is a Phase 2, randomised, double-blind, placebo-controlled trial evaluating pemvidutide in adults with alcohol-associated liver disease (ALD). The study targets the dual hepatic and metabolic mechanism of pemvidutide — its glucagon receptor agonism directly reduces liver fat, inflammation and fibrosis, while GLP-1 receptor activation provides appetite suppression and weight loss. ALD is a distinct indication from MASH with active alcohol exposure as the primary driver. Trial was initiated in late 2025; per Altimmune's August 12, 2026 business update, patient enrollment has been completed, with enrollment completion previously guided for Q3 2026. FDA has granted Fast Track Designation for pemvidutide in ALD.

Phase 3 Study of the Efficacy, Safety, and Clinical Outcomes of Pemvidutide in MASH (PERFORMA)

PERFORMA is Altimmune's global, randomised, double-blind, placebo-controlled, event-driven Phase 3 registrational trial of pemvidutide in adults with metabolic dysfunction-associated steatohepatitis (MASH) and confirmed moderate-to-advanced liver fibrosis (F2-F3), initiated August 3, 2026 following positive IMPACT Phase 2b data and incorporating FDA/EU regulatory feedback. Cohort 1 (~990 patients, biopsy-confirmed) supports an accelerated-approval pathway via a primary efficacy endpoint of MASH resolution and/or fibrosis improvement at 52 weeks; Cohort 2 (~800 patients, non-invasive-test-confirmed fibrosis) adds to the safety dataset. Both cohorts will support final regulatory approval based on liver-related clinical outcomes at approximately 60 months. Dosing uses a simplified 1-2 step monthly titration from 1.2 mg to 1.8 mg or 2.4 mg. The trial integrates the FDA-qualified AIM-MASH AI Assist tool to standardize histological assessment. 52-week data readout anticipated in 2029.