Altimmune 的 pemvidutide 在酒精使用障碍 2 期 ReCLAIM 研究中达到主要终点

An experimental drug targeting both GLP-1 and glucagon receptors has curbed heavy drinking in a phase 2 trial providing hope that the ubiquitous weight loss meds can be effectively harnessed against alcohol use disorder (AUD).
In the Reclaim study, patients treated with injections of Altimmune’s pemvidutide had an average of 4.2 fewer heaving drinking days over a 24-week period compared to their prior baselines, the Maryland biotech announced today. Those given placebo saw a 2.75-day reduction, notching pemvidutide a statistically significant win on the trial’s primary endpoint.
Pemvidutide also bested placebo by dropping more patients’ World Health Organization Risk Drinking Levels score by two levels, increasing the number of abstinent days and sharply cutting the amount of phosphatidylethanol, a tell-tale sign of heavy drinking, in the blood.
Altimmune’s stock enjoyed a bump up from $2.96 per share at yesterday’s close to a high of $3.18 when trading opened this morning, but then settled back down by late morning.
“These data reflect pemvidutide’s strong and consistent efficacy across important measures of drinking behavior, together with a generally favorable tolerability profile in this difficult-to-treat disorder,” Christophe Arbet-Engels, M.D., Ph.D., Altimmune’s chief medical officer, said in the release.
Analysts from William Blair wrote in a note today that pemvidutide “demonstrated unequivocal clinical benefits” in AUD.
“We believe the 38% reduction (compared with an increase of 5.9% for placebo) in serum phosphatidylethanol (direct biomarker for alcohol consumption) offered the strongest validation for pemvidutide in this indication,” the analysts wrote.
The safety profile seen in the trial was consistent with past tests of pemvidutide, the analysts added. Most of the side effects reported by Altimmune were gastrointestinal, which is common for GLP-1 drugs. Five patients discontinued pemvidutide due to issues like vomiting, constipation, fatigue and a worsening of hemorrhoids, while nobody on placebo stopped treatment.
While Novo Nordisk’s GLP-1 rock star semaglutide has shown promise in AUD, “pemvidutide appears to exhibit a more robust clinical profile than short-duration low-dose semaglutide,” the analysts wrote.
However, Novo’s chief competitor and GLP-1 juggernaut Eli Lilly also has a next-gen dual-acting candidate in the works, a molecule called brenipatide that is currently in a pair of phase 3 trials for AUD. Brenipatide targets GLP-1 and fellow incretin gastric inhibitory polypeptide or GIP.
Arbet-Engels believes pemvidutide’s dual-action mechanism sets it apart from the crowd, he said in the release.
“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.
Altimmune intends to next meet with the FDA to discuss the results and plan a potential path forward for pemvidutide in the indication, the company said. The biotech is also set to launch a phase 3 trial of the drug candidate in metabolic dysfunction-associated steatohepatitis later this year.
Given Lilly’s two trials are both meant to enroll 1,100 patients, “we believe Altimmune will require additional capital to fund a pivotal program in AUD,” the William Blair analysts wrote. The company held $535 million in cash and cash equivalents as of April 30.