Weight-Loss Drug Moves Into Alcohol Addiction Treatment: Phase 2 Pemvidutide Trial Reduces Heavy Drinking

A drug originally developed for metabolic and liver diseases is seeking to move into the treatment landscape for alcohol use disorder. Altimmune announced topline results from the Phase 2 RECLAIM trial: participants receiving pemvidutide reduced their weekly heavy drinking days by 4.20 days from baseline, compared with a reduction of 2.75 days in the placebo group. The between-group difference was 1.45 days and was statistically significant (p=0.0014).

RECLAIM was a multicenter, double-blind, placebo-controlled trial that enrolled 100 adults who were overweight or obese and had moderate to severe alcohol use disorder. Participants were assigned in a one-to-one ratio to receive a once-weekly subcutaneous injection of pemvidutide 2.4 mg or placebo for 24 weeks. The trial defined a “heavy drinking day” as at least five drinks in one day for men and at least four drinks for women.

The effect was not limited to the primary endpoint. A two-level reduction in the World Health Organization drinking risk classification was achieved by 64.4% of the pemvidutide group and 34.8% of the placebo group. The proportions with no heavy drinking days at all during the final four weeks of treatment were 42.2% and 17.4%, respectively. Blood phosphatidylethanol (PEth), a biomarker that can reflect alcohol intake, also improved in favor of the treatment group, providing a layer of objective corroboration for self-reported drinking records.

Pemvidutide activates both glucagon and GLP-1 receptors. In addition to regulating appetite, GLP-1 signaling may affect craving and reward circuits, while the glucagon receptor has a more direct effect on liver metabolism. This biological rationale could allow the drug to address drinking behavior, body weight, and alcohol-related liver injury simultaneously, but this trial did not establish how much each of these mechanisms contributed, nor can it determine whether dual agonism is superior to GLP-1 drugs alone.

The efficacy signal came with a clear tolerability cost. The incidence of nausea was 44% in the treatment group and 24% in the placebo group, constipation was 26% and 6%, and vomiting was 18% and 6%, respectively. Five participants receiving pemvidutide discontinued treatment because of adverse events considered related to the drug. The treatment group also had one serious event of hyponatremia, which the principal investigator judged to be possibly related to the drug. Overall discontinuation rates were 20% in the treatment group and 22% in the placebo group.

These findings come from a limited-size Phase 2 trial that included only people who were overweight or obese, and they currently remain company-announced topline data that have not undergone peer review. Direct cross-trial comparisons with drugs such as semaglutide are also prone to confounding from differences in populations, endpoints, and study designs. Altimmune plans to hold an end-of-Phase 2 meeting with the U.S. Food and Drug Administration. Whether the drug can advance into larger trials and whether its effects are durable and applicable to a broader patient population will determine how far this treatment approach can go.