Maryland-based Altimmune, Inc. (Nasdaq: ALT) reported positive topline results from the RECLAIM study, a Phase II trial of pemvidutide in moderate-to-severe alcohol use disorder, positioning the drug as the first dual glucagon/GLP-1 receptor agonist to demonstrate statistically significant efficacy in this indication. The data are notable not only for the primary endpoint result but because two secondary endpoints — zero heavy drinking days and a two-level reduction in WHO Risk Drinking Levels — are FDA-recognized registrational endpoints, giving Altimmune a cleaner path into a pivotal program.
The FDA has approved only three drugs for AUD — disulfiram, naltrexone, and acamprosate — and all three are used by fewer than 2% of patients with the disorder. No approved agent addresses the metabolic and hepatic comorbidities common in this population.
Pemvidutide activates glucagon and GLP-1 receptors in a balanced 1:1 ratio. GLP-1 receptor engagement suppresses appetite and may modulate craving and reward pathways, while glucagon receptor activation drives direct hepatic effects including reductions in liver fat and fibrosis — a potentially relevant mechanism in a population where alcohol-related liver damage is prevalent.
In RECLAIM, approximately 100 patients with moderate-to-severe AUD and BMI above 25 kg/m² were randomized 1:1 to pemvidutide 2.4 mg or placebo once weekly for 24 weeks. The primary endpoint — change from baseline in heavy drinking days per week — showed a least-squares mean reduction of 4.20 in the pemvidutide arm versus 2.75 with placebo, a treatment difference of 1.45 (p=0.0014). On the two registrational secondary endpoints, 64.4% of pemvidutide-treated patients achieved a two-level WHO Risk Drinking Level reduction versus 34.8% on placebo (odds ratio 3.31; p=0.0049), and 42.2% reached zero heavy drinking days in weeks 21–24 versus 17.4% (odds ratio 3.84; p=0.0066). Serum phosphatidylethanol, an objective biomarker of alcohol intake, fell by a least-squares mean of 153.4 units in the pemvidutide arm versus a 22.0-unit increase with placebo (p<0.0001). Body weight declined by a placebo-adjusted 9.1% at 24 weeks with no evidence of plateauing.
Gastrointestinal adverse events were more frequent with pemvidutide — nausea 44% versus 24%, constipation 26% versus 6% — and five patients (10%) discontinued due to drug-related adverse events. Treatment discontinuation rates were similar between arms (20% pemvidutide, 22% placebo). One serious adverse event, hyponatremia, was deemed possibly related to study drug.