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Altimmune Announces Positive Topline Results from Reclaim Phase 2 Trial of Pemvidutide in Alcohol Use Disorder
Altimmune, Inc. announced positive topline results from the RECLAIM Phase 2 trial evaluating pemvidutide, an investigational balanced glucagon/GLP-1 dual receptor agonist, in patients with moderate to severe alcohol use disorder (AUD). The trial met its primary endpoint with a highly statistically significant reduction in heavy drinking days (HDD) versus placebo, with consistent positive results across important secondary endpoints, including the World Health Organization (WHO) Risk Drinking Levels (RDL), zero HDD and phosphatidyl ethanol (PEth) levels. A generally favorable tolerability profile was observed in the trial. The Company plans to request an End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) based on the results of the trial. Pemvidutide 2.4 mg delivered a statistically significant and clinically meaningful reduction in heavy drinking days, the primary endpoint of the trial. Important secondary endpoints were also met, including two-level reduction in WHO risk drinking levels and zero heavy drinking days, both of which are recognized by the FDA as registrational endpoints. Efficacy Data: Change from baseline in HDD/Week at Week 24 (Primary Endpoint): Placebo -2.75 (LS mean), Pemvidutide -4.20 (LS mean), Treatment Effect -1.45 (LS mean difference), P-value 0.0014. 2-level Reduction in WHO-RDL: Placebo 34.8% (16/46), Pemvidutide 64.4% (29/45), Odds Ratio 3.31, P-value 0.0049. Zero HDD in Week 21 through Week 24: Placebo 17.4% (8/46), Pemvidutide 42.2% (19/45), Odds Ratio 3.84, P-value 0.0066. Change from baseline in Percent of Days with Abstinence: Placebo 20.5% (LS mean), Pemvidutide 38.9% (LS mean), 18.4% (LS mean difference), P-value 0.0075. Change from baseline in Serum PEth at Week 24: Placebo 22.0 (LS mean), Pemvidutide -153.4 (LS mean), -175.3 (LS mean difference). Key efficacy results included: Statistically significant reduction in the primary endpoint of HDD per week versus placebo (p=0.0014). Statistically significant results on secondary endpoints, including two that are registrational endpoints: Two-level reduction in WHO Risk Drinking Levels versus placebo (p=0.0049), Zero heavy drinking days versus placebo (p=0.0066). Statistically significant change in percent of days with abstinence versus placebo (p=0.0075). Statistically significant reduction in PEth levels versus placebo. The new, simple two-step titration for the 2.4 mg dose may improve gastrointestinal (GI) tolerability compared to prior pemvidutide titration schemes. The majority of adverse events were mild to moderate in severity. There was one serious adverse event (SAE) (hyponatremia) in the pemvidutide arm that was deemed possibly related to treatment drug by the principal investigator. Based on these data, Altimmune plans to request an End-of-Phase 2 (EOP2) meeting with the FDA to discuss the path forward for pemvidutide in AUD. Results from the RECLAIM trial will be submitted for presentation at a forthcoming medical conference and for publication in a peer-reviewed journal. RECLAIM (NCT06987513) is a Phase 2 trial evaluating the safety and efficacy of pemvidutide in Alcohol Use Disorder (AUD) patients with BMI >25 kg/m2, and is the first Phase 2 multicenter study evaluating a dual glucagon-GLP-1 agonist in AUD to report results. Approximately 100 patients were randomized 1:1 to receive either 2.4 mg pemvidutide or placebo once weekly for 24 weeks. The primary endpoint of the trial was the change from baseline in the average number of heavy drinking days (HDD) per week, with secondary endpoints including the proportion of patients achieving a 2-level reduction in World Health Organization (WHO) Risk Drinking Levels (RDL), zero HDD, and absolute change from baseline in average levels of phosphatidylethanol (PEth), an objective serum biomarker of alcohol intake. The 2-level reduction in WHO risk drinking levels and zero HDD are recognized by the FDA as registrational endpoints. Pemvidutide is a novel, investigational peptide with balanced 1:1 glucagon/GLP-1 dual receptor agonist activity, in development for the treatment of metabolic dysfunction-associated steatohepatitis (MASH), alcohol use disorder (AUD) and alcohol-associated liver disease (ALD). The activation of glucagon receptors results in direct effects on the liver, including reductions in liver fat, inflammation and fibrosis, while GLP-1 receptors mediate metabolic effects such as appetite suppression and weight loss, and may play a role in pathways related to craving and reward. The FDA granted Fast Track designations to pemvidutide for the treatment of MASH and AUD, as well as Breakthrough Therapy Designation for MASH. In December 2025, the Company announced 48-week data from the IMPACT Phase 2b trial in MASH. In July 2026, the Company announced results from the RECLAIM Phase 2 trial in AUD. The RESTORE trial in ALD was initiated in July 2025, and enrollment completion is expected in the third quarter 2026. The Company plans to initiate the PERFORMA Phase 3 trial, a multinational, randomized, double-blind, placebo-controlled, parallel-group study of pemvidutide in patients with MASH in the third quarter of 2026.