Pemvidutide reduces heavy drinking days in alcohol use disorder in Phase 2 RECLAIM trial – Altimmune

Altimmune has presented positive results from the Phase 2 RECLAIM trial of pemvidutide in adults with moderate-to-severe alcohol use disorder (AUD). Pemvidutide is an investigational, balanced 1:1 glucagon/GLP-1 dual receptor agonist. The data were presented in a late-breaker session at The Liver Meeting 2026, hosted by the American Association for the Study of Liver Diseases (AASLD) in Denver, Colorado.

RECLAIM is the first multicentre Phase 2 study of a dual glucagon/GLP-1 agonist in AUD to report results. Approximately 100 adults with AUD and a BMI above 25 kg/m² were randomised 1:1 to once-weekly pemvidutide 2.4 mg or placebo for 24 weeks. All participants also received standardised behavioural intervention.

Drinking outcomes

The trial met its primary endpoint. Heavy drinking days (HDDs) per week fell by 4.20 days with pemvidutide, compared with 2.75 days with placebo (treatment difference −1.45 days; p=0.0014). The two groups separated as early as Week 4. Key secondary endpoints included:

• 42.2% of patients on pemvidutide had zero HDDs, versus 17.4% on placebo (OR 3.8; p=0.0066)
• 64.4% achieved a two-level reduction in WHO Risk Drinking Level, versus 34.8% (OR 3.3; p=0.0049)
• The percentage of abstinent days rose to 38.9%, versus 20.5% (p=0.0075)
• Phosphatidylethanol (PEth), an objective blood marker of alcohol intake, fell by 153.4 ng/mL, compared with a 22.0 ng/mL rise on placebo (difference −175.4 ng/mL; p<0.0001)

The FDA recognises zero HDDs and a two-level WHO risk reduction as registrational endpoints.

Weight and liver health

Participants on pemvidutide lost 8.7% of their body weight on average, while those on placebo gained 0.4% (difference −9.1%; p<0.0001). Among patients with elevated baseline FIB-4 (≥1.3), 50% normalised to below 1.3, compared with 17% on placebo.

“These results, validated by PEth concentration, a biochemical measure of alcohol use, alongside improvements in weight and markers of liver health, suggest that pemvidutide may offer a novel approach to addressing the interconnected health consequences of AUD,” said Henry R. Kranzler, MD, Director of the Center for Studies of Addiction at the University of Pennsylvania’s Perelman School of Medicine.

Safety

Adverse events were mainly mild to moderate. Gastrointestinal events were the most common: nausea (44% vs 24% on placebo), vomiting (18% vs 6%), diarrhoea (20% vs 10%) and constipation (26% vs 6%). Discontinuation rates were similar in both arms (20% vs 22%).

Altimmune also presented new 48-week data from the IMPACT Phase 2b study in MASH. Compared with placebo, pemvidutide reduced liver stiffness, ELF score, liver fat and ALT.

Altimmune will hold an End-of-Phase 2 meeting with the FDA in December to discuss the design of a Phase 3 registrational programme in AUD.