FDA Grants Fast Track Designation to Pemvidutide for Treatment of Alcohol Use Disorder

itakdalee/AdobeStock

Altimmune today announced that the US Food and Drug Administration (FDA) has granted Fast Track designation to pemvidutide for the treatment of alcohol use disorder (AUD). Pemvidutide is a novel, investigational, peptide-based 1:1 GLP-1/glucagon dual receptor agonist.¹

The phase 2 trial RECLAIM (NCT06987513) evaluating the safety and efficacy of pemvidutide in AUD is currently enrolling. Investigators anticipate needing approximately 100 participants, who will be randomly assigned 1:1 to receive either 2.4 mg pemvidutide or placebo once weekly for 24 weeks. The primary endpoint of the trial is the change from baseline in the average number of heavy drinking days, with key secondary endpoints including the proportion of subjects achieving a 2-level reduction in World Health Organization (WHO) risk drinking level and absolute change from baseline in average levels of phosphatidylethanol (PEth), a serum biomarker of alcohol intake. The trial began enrolling in May 2025.

“Despite an estimated prevalence of AUD in more than 28 million adults in the US alone, the scarcity of effective treatment options has created a sizeable treatment gap in AUD, with only 2% being treated with medication today,” said Vipin K. Garg, PhD, the president and CEO of Altimmune. “Currently approved therapies have shown limited effectiveness and fail to adequately address the comorbidities of AUD, such as hepatic steatosis, hyperlipidemia and hypertension, or other comorbidities of obesity from which individuals with AUD often suffer. The Fast Track designation recognizes both the urgent unmet need associated with AUD and the potential for pemvidutide to play a role in the treatment of this serious condition.”

Pemvidutide is in development for not only the treatment of AUD, but also metabolic dysfunction-associated steatohepatitis (MASH), alcohol-associated liver disease (ALD), and obesity. Pemvidutide works via activation of the GLP-1 and glucagon receptors, which is believed to mimic the complementary effects of diet and exercise on weight loss, with GLP-1 suppressing appetite and glucagon increasing energy expenditure. Investigators also recognize glucagon has direct effects on hepatic fat metabolism, which could lead to rapid reductions in levels of liver fat and serum lipids.

The FDA previously granted Fast Track designation to pemvidutide for the treatment of MASH. In the ongoing IMPACT phase 2b trial, at week 24, once-weekly pemvidutide demonstrated statistically significant MASH resolution without worsening of fibrosis, positive trends in liver fibrosis stage improvement without worsening of MASH, statistically significant reductions in noninvasive tests of fibrosis, weight loss, and liver fat content, and improvements in blood pressure.² In a post-hoc AI-based analysis of the biopsies from the IMPACT trial, pemvidutide also achieved a statistically significant reduction in liver fibrosis. In previous trials, pemvidutide also demonstrated class-leading lean mass preservation and robust reductions in triglycerides and LDL cholesterol. In terms of safety profile, pemvidutide was well tolerated in the IMPACT trial and demonstrated potentially best-in-class tolerability among drugs in development for MASH with very low rates of discontinuation due to adverse events. The ongoing IMPACT phase 2b MASH trial 48-week readout is expected in late 2025.

In terms of additional research, the phase 2 RECLAIM trial in AUD and the phase 2 RESTORE 2 trial in ALD were initiated in May 2025 and July 2025, respectively.

“There is a clear scientific rationale for the use of pemvidutide in AUD. Fatty liver develops in up to 90% of problem drinkers and places individuals with AUD at risk for alcohol-associated hepatitis. Treatment with GLP-1 agonists is recognized to reduce cravings for alcohol, while glucagon is recognized to reduce hepatic steatosis and inflammation. In a preclinical model of free-choice alcohol use, pemvidutide was shown to produce rapid and significant reduction in alcohol intake,” said Scott Harris, MD, the chief medical officer of Altimmune. “We look forward to evaluating the potential of pemvidutide in the treatment of AUD through the ongoing RECLAIM trial.”

References

1. Altimmune Announces FDA Fast Track designation for pemvidutide in alcohol use disorder (AUD). News release. August 19, 2025. https://ir.altimmune.com/news-releases/news-release-details/altimmune-announces-fda-fast-track-designation-pemvidutide

2. Altimmune announces positive topline results from the IMPACT phase 2b trial of pemvidutide in the treatment of MASH. News release. June 26, 2025. Accessed Augus 19, 2025. https://ir.altimmune.com/news-releases/news-release-details/altimmune-announces-positive-topline-results-impact-phase-2b