Altimmune Reports Reduced Heavy Drinking With Pemvidutide in Phase 2 Trial

Altimmune announced detailed results from its Phase 2 RECLAIM study on November 9, 2026, showing that once-weekly pemvidutide significantly reduced heavy drinking days and improved other measures of alcohol consumption in adults with moderate-to-severe alcohol use disorder (AUD). The findings were presented in a late-breaking session at The Liver Meeting 2026, hosted by the American Association for the Study of Liver Diseases (AASLD) in Denver, Colorado.

At Week 24, pemvidutide achieved a statistically significant reduction in heavy drinking days compared with placebo, alongside higher rates of abstinence and improvements in phosphatidylethanol (PEth), an objective biomarker of alcohol intake. Participants also experienced substantial weight loss and improvements in a non-invasive liver fibrosis risk measure. Altimmune plans to meet with the US Food and Drug Administration (FDA) in December 2026 to discuss the design of a Phase 3 registrational programme.

RECLAIM Study Design and Primary Endpoint

RECLAIM (NCT06987513) was a Phase 2, randomized, double-blind, placebo-controlled, multicentre study evaluating pemvidutide in adults with AUD and a body mass index (BMI) above 25 kg/m². Approximately 100 participants were randomized 1:1 to receive once-weekly pemvidutide 2.4 mg or placebo for 24 weeks, alongside a standardized behavioural intervention.

The primary endpoint was the change from baseline in the average number of heavy drinking days (HDD) per week, defined as five or more drinks per day for men and four or more for women. Secondary endpoints included a two-level reduction in World Health Organization (WHO) Risk Drinking Level (RDL), achievement of zero HDD, and changes in PEth concentrations.

 Pemvidutide Reduces Heavy Drinking and Improves Abstinence

Pemvidutide met the primary endpoint, reducing HDD by 4.20 days per week compared with 2.75 days with placebo. The treatment difference was 1.45 fewer heavy drinking days per week (), with separation from placebo observed as early as Week 4. The result remained statistically significant in a sensitivity analysis ().

Key secondary endpoints demonstrated broad treatment benefits:

• Zero Heavy Drinking Days: Achieved by 42.2% of pemvidutide-treated participants versus 17.4% with placebo (; ).
• WHO Risk Drinking Level: A two-level reduction occurred in 64.4% versus 34.8%, respectively (; ).
• Abstinent Days: Increased to 38.9% compared with 20.5% with placebo ().
• Alcohol Intake: Drinks per drinking day declined by 4.9 with pemvidutide versus 3.8 with placebo.
• PEth Biomarker: Concentrations decreased by  with pemvidutide, compared with an increase of  with placebo (treatment difference ; ).

The reduction in PEth provides objective biochemical validation of reduced alcohol intake, reinforcing self-reported consumption data.

Weight Loss and Liver Health Findings

Participants receiving pemvidutide achieved mean weight loss of 8.7% at Week 24, compared with a 0.4% weight gain with placebo, representing a treatment difference of 9.1 percentage points ().

Among participants with elevated baseline FIB-4 scores (), a non-invasive measure used to assess hepatic fibrosis risk, 50% achieved normalization to below 1.3 compared with 17% in the placebo group. These findings suggest potential metabolic and liver-related benefits alongside reduced alcohol consumption. However, FIB-4 normalization does not establish histological fibrosis regression or demonstrate long-term clinical liver outcomes.

Safety and Tolerability

Pemvidutide was generally well tolerated, with adverse events primarily mild to moderate. Gastrointestinal events were more frequent than with placebo, including:

• Nausea: 44% vs 24%
• Vomiting: 18% vs 6%
• Diarrhoea: 20% vs 10%
• Constipation: 26% vs 6%

Treatment discontinuation rates were comparable between groups, at 20% with pemvidutide and 22% with placebo.

Additional IMPACT Findings Strengthen MASH Development Programme

Altimmune also presented 48-week analyses from its Phase 2b IMPACT study evaluating pemvidutide in metabolic dysfunction-associated steatohepatitis (MASH). Treatment produced concurrent reductions in two non-invasive fibrosis measures liver stiffness and the Enhanced Liver Fibrosis (ELF) score alongside reductions in liver fat and alanine aminotransferase (ALT) compared with placebo.

Separate IMPACT analyses showed that gastrointestinal adverse events were predominantly mild to moderate, with no severe gastrointestinal treatment-emergent events reported. Discontinuations due to adverse events were lower with pemvidutide than with placebo. These findings add to the evidence supporting pemvidutide’s development in MASH, although changes in non-invasive markers should not be interpreted as confirmed histological fibrosis improvement.

Clinical Implications

Pemvidutide is an investigational peptide with balanced 1:1 glucagon/GLP-1 dual receptor agonist activity. Glucagon receptor activation is associated with direct hepatic effects, while GLP-1 receptor activity contributes to metabolic effects, including appetite suppression, weight loss, and modulation of central craving and reward pathways.

The FDA has granted Fast Track designation for pemvidutide in both AUD and MASH, alongside Breakthrough Therapy Designation for MASH. Altimmune initiated the Phase 3 PERFORMA study in MASH in July 2026 and completed enrolment in the Phase 2 RESTORE study in alcohol-associated liver disease (ALD) in August 2026.

While RECLAIM provides encouraging evidence in AUD for adults with elevated BMI, conclusions remain limited by the trial’s size (~100 participants), 24-week duration, substantial background response in the placebo/behavioural intervention arm, and lack of head-to-head comparison with established AUD therapies. The planned December 2026 End-of-Phase 2 FDA meeting will guide the design of larger Phase 3 trials needed to confirm durable efficacy and safety.

Reference

Altimmune Presents Positive Late-Breaking Pemvidutide Data at AASLD The Liver Meeting® 2026 in Patients with Alcohol Use Disorder, altimmune, 09 November 2026

RECLAIM STUDY: Phase 2 Study of the Efficacy and Safety of Pemvidutide in the Treatment of Alcohol Use Disorder (AUD) in Subjects with Obesity or Overweight, ClinicalTrials.gov ID NCT06987513