Altimmune reports positive Phase 2 results for pemvidutide in alcohol use disorder

Altimmune, a biopharmaceutical company, said its investigational drug pemvidutide met the main goal of a Phase 2 trial called RECLAIM in people with moderate to severe alcohol use disorder (AUD), reducing heavy drinking days by a statistically significant margin compared with placebo ^[1]. The company plans to ask the FDA for an End-of-Phase 2 meeting to discuss next steps ^[1].

Pemvidutide is not semaglutide or tirzepatide. It is a different molecule that activates both glucagon and GLP-1 receptors in a 1:1 balance, and it is being developed for liver diseases including MASH and alcohol-associated liver disease, not yet approved for any use ^[1].

In the trial, about 100 adults with AUD and a body mass index over 25 were randomly assigned to weekly pemvidutide at 2.4 mg or placebo for 24 weeks ^[1]. Patients on pemvidutide reduced heavy drinking days per week by 4.20 on average, versus 2.75 for placebo, a difference of 1.45 heavy drinking days that was highly statistically significant (p=0.0014) ^[1]. On a secondary measure, 64.4% of pemvidutide patients achieved a two-level drop in WHO Risk Drinking Levels, compared with 34.8% on placebo, an outcome the FDA recognizes as a registrational endpoint ^[1]. About 42.2% of pemvidutide patients had zero heavy drinking days in the final month of the study, versus 17.4% on placebo ^[1]. A blood biomarker of alcohol intake, PEth, fell sharply in the drug group (-153.4) while it rose slightly in the placebo group (22.0), a difference the company called highly significant (p<0.0001) ^[1]. Patients on pemvidutide also lost more weight, with a placebo-adjusted difference of 9.1% at 24 weeks ^[1].

Side effects were more common with pemvidutide than placebo. Nausea occurred in 44% of drug-treated patients versus 24% on placebo, vomiting in 18% versus 6%, diarrhea in 20% versus 10%, and constipation in 26% versus 6% ^[1]. Serious adverse events were rare, at 4% for pemvidutide and 2% for placebo, and one serious case of low blood sodium was judged possibly related to the drug ^[1]. Discontinuation rates were similar between groups, at 20% for pemvidutide and 22% for placebo ^[1]. Altimmune's chief medical officer said the drug's effect on the liver, through its glucagon activity, could offer benefits beyond what GLP-1-only drugs provide, since heavy alcohol use damages the liver directly ^[1].

Why it matters for patients

The FDA has approved only three drugs for AUD, and fewer than 2% of the estimated 28 million U.S. adults with the condition use them, according to Altimmune, largely because current options have limited effectiveness ^[1]. If these results hold up in larger trials, pemvidutide could become a new option for people who have moderate or severe AUD and have not found existing treatments helpful. It is worth noting this is not a semaglutide or tirzepatide product; it works through a different combined mechanism, and it is still years away from being available even if later trials succeed ^[1].

The gastrointestinal side effects seen here, especially nausea, vomiting, and constipation, are similar in kind to those reported with other GLP-1-class drugs, though rates and severity can differ by drug and population ^[1]. Because this is one mid-size trial of about 100 people, more data will be needed to confirm both the size of the benefit and the safety profile before any regulatory decision is made ^[1].

What happens next

Altimmune plans to request an End-of-Phase 2 meeting with the FDA to map out next steps for pemvidutide in AUD ^[1]. The company also said full RECLAIM results will be submitted for presentation at a medical conference and for publication in a peer-reviewed journal ^[1]. Separately, Altimmune's RESTORE trial testing pemvidutide in alcohol-associated liver disease was expected to complete enrollment in the third quarter of 2026, and a Phase 3 trial in MASH, called PERFORMA, was planned to start in the same quarter ^[1]. No timeline for a possible AUD approval has been given ^[1].