Altimmune alcohol use disorder drug hits the mark in phase 2
A dual GLP-1 and glucagon agonist developed by Altimmune has been shown to reduce drinking in people with alcohol use disorder (AUD), adding to the evidence that incretin therapies may have a role to play in addiction.
In the phase 2 RECLAIM trial, a 2.4 mg subcutaneous injection of pemvidutide, given once a week, achieved a statistically significant reduction in weekly heavy drinking days (HDD), compared to placebo, in patients with moderate to severe AUD.
Over 24 weeks of follow-up, the pemvidutide group saw a 4.2-day reduction in HDD, compared to 2.75 days with placebo, with a two-level reduction on the WHO Risk Drinking Levels (RDL) scale seen in 64.4% and 34.8%, respectively.
In addition, the proportion of patients with no HDDs at all in weeks 21 to 24 was 42.2% with pemvidutide and 17.4% with placebo, while Altimmune's drug was associated with 38.9% fully abstinent days, compared to 20.5% in the control group.
Other incretin drugs acting on the GLP-1 pathway, including Novo Nordisk's semaglutide, have also shown efficacy in reducing alcohol intake in AUD, with researchers speculating they may work by reducing cravings.
Altimmune said that the results of the 100-subject study include clinical endpoints that are recognised by the FDA as being suitable for registration trials, and it plans to meet with the FDA to discuss a potential route to market for pemvidutide in AUD.
The drug is also being developed for metabolic dysfunction-associated steatohepatitis (MASH), with a phase 3 trial due to start later this year, and in patients with alcohol-associated liver disease (ALD), so Altimmune is sidestepping the competitive weight-loss and diabetes markets currently accounting for most incretin drug sales.
The company's chief medical officer, Christophe Arbet-Engels, called the results in AUD "compelling" with "strong and consistent efficacy across important measures of drinking behaviour, together with a generally favourable tolerability profile."
Like other GLP-1-acting drugs, pemvidutide caused gastrointestinal side effects such as nausea and vomiting, but discontinuation rates were similar to placebo, and the company has developed a new, two-step titration that can improve GI tolerability.
Moreover, "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," added Arbet-Engels. That could differentiate the drug from GLP-1 drugs being developed for AUD, such as semaglutide, Eli Lilly's brenipatide, and Baseline Therapeutics' BT-001.
If these encouraging results are backed up in further trials, pemvidutide could offer an alternative to current AUD therapies like naltrexone, acamprosate, and disulfiram, which alter brain chemistry and have limited efficacy.
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