GLP-1 drugs first made their mark in diabetes and obesity, but many research efforts are underway to bring such therapies to more indications. Altimmune now has mid-stage clinical trial results showing its molecule designed to target two gut hormone receptors led to a reduction in alcohol consumption.
According to the preliminary data reported Tuesday, once-weekly injections of the Altimmune drug, pemvidutide, achieved a statistically significant reduction in heavy drinking days, meeting the main goal of the Phase 2 trial. Based on these results, the company plans to meet with the FDA to discuss the path forward for the drug in alcohol use disorder.
Drugs are already available that pair the activation of GLP-1 receptors with the additional mechanism of hitting another target. The most visible example might be tirzepatide, the Eli Lilly peptide — marketed as Mounjaro for type 2 diabetes and as Zepbound for obesity — designed to bind to and activate the GLP-1 and GIP receptors.
Altimmune’s pemvidutide pairs GLP-1 agonism with the activation of glucagon receptors. The Gaithersburg, Maryland-based biotech specializes in developing drugs for the liver. The company says activating glucagon receptors leads to reduction in liver fat, inflammation, and the organ scarring called fibrosis. The company adds that targeting of GLP-1 receptors by this peptide leads to appetite suppression and weight loss that may play a role in pathways related to craving and reward.
The placebo-controlled Phase 2 test of pemvidutide enrolled 100 men and women with both alcohol use disorder and obesity. These participants reported at least 28 drinks per week for men and 21 drinks per week for women. The main trial goal is measuring the change from baseline in the average number of heavy drinking days per week. A heavy drinking day is defined as five or more drinks per day for men and four or more daily drinks for women.
At week 24, the preliminary results show heavy drinking days per week were reduced by an average of 4.2 days in the study drug group versus a reduction of 2.75 days in the placebo arm. Furthermore, Altimmune said 42.2% of participants in the pemvidutide arm achieved zero heavy drinking days, which was more than twice that of the placebo group. Achieving zero heavy drinking days is an important trial goal for a registrational study in alcohol use disorder, the company said in an investor presentation.
Pemvidutide was generally well tolerated by trial participants, and Altimmune said most adverse events were classified as mild to moderate. One serious adverse event, hyponatremia (low levels of sodium in the blood), was reported in the pemvidutide arm that the principal investor deemed was possibly related to the study drug. Altimmune said more detailed results will be submitted for publication in a peer-reviewed journal and presented at a future medical conference. In the company’s announcement of the results, Altimmune Chief Medical Officer Christophe Arbet-Engels said the data show strong and consistent efficacy across important measures of drinking behavior.
“Given the known detrimental effects of alcohol on the liver, the liver-directed impact of glucagon in pemvidutide may provide further benefit in the treatment of AUD over GLP-1 alone, underscoring pemvidutide’s promising potential differentiation,” he said.
Differentiation could be key. Acknowledging all of the caveats that come with cross-trial comparisons, Leerink Partners analyst Thomas Smith said in a research note that initial results for Altimmune’s drug look encouraging compared to Novo Nordisk’s semaglutide, the GLP-1-targeting peptide component in Ozempic and Wegovy. Pemvidutide’s results de-risk the drug’s clinical and regulatory path forward, Smith said.
William Blair analysts Andy Hsieh and Alexandra Ramsey said in a research note that Altimmune’s drug appears to show a more robust clinical profile than short-duration, low-dose semaglutide. But they noted that Lilly is ahead with brenipatide, a GLP-1 and GIP agonist currently in Phase 3 testing in alcohol use disorder; a data readout is expected in 2028. Altimmune will likely require additional capital for its own pivotal clinical trial in this indication, they said.
The most advanced indication for pemvidutide is actually the fatty liver disease metabolic-dysfunction associated steatohepatitis (MASH). Altimmune said it is on track to start a placebo-controlled Phase 3 test of its drug in MASH in the current quarter. The William Blair analysts acknowledge that the Altimmune drug has demonstrated therapeutic activity in this indication, but they do not believe the drug’s results from the Phase 2b study, called IMPACT, demonstrated clear clinical differentiation from other MASH drugs. This field includes Madrigal Pharmaceuticals’ Rezdiffra, the first FDA-approved MASH drug. Contenders include Boehringer Ingelheim’s survodutide and two from Lilly, tirzepatide and the triple agonist retatrutide.
“Without liver biopsies from the 48-week timepoint in the IMPACT trial, it is our view that the available data cannot meaningfully de-risk pemvidutide prior to Phase 3 initiation, which is expected to occur this quarter,” Hsieh and Ramsey said in the note.
Photo: axelbueckert, Getty Images
