Altimmune's Pemvidutide Shows Mixed Results in Phase IIb MASH Study

Altimmune, a clinical-stage biopharmaceutical company, faced a significant setback as its dual GLP-1/glucagon agonist pemvidutide delivered mixed results in a Phase IIb trial for metabolic dysfunction-associated steatohepatitis (MASH). The news sent shockwaves through the biotech sector, causing Altimmune's stock to plummet 53% following the data readout.

IMPACT Trial Results: A Double-Edged Sword

The IMPACT trial, which enrolled over 200 patients with biopsy-confirmed MASH and stage F2 or F3 fibrosis, demonstrated pemvidutide's ability to resolve MASH without worsening fibrosis. At 24 weeks, 59.1% of patients in the 1.2-mg dose group and 52.1% in the 1.8-mg dose group achieved MASH resolution, compared to only 19.1% in the placebo group.

However, the drug failed to meet the critical endpoint of improving fibrosis without worsening MASH, a result that investors and analysts viewed as crucial for differentiation in the competitive MASH treatment landscape. William Blair analysts described the outcome as "underwhelming," noting that fibrosis improvement is closely correlated with liver failure, death, and progression to cirrhosis or hepatocellular carcinoma.

Secondary Endpoints and Weight Loss

Pemvidutide did show promise in several secondary endpoints, including reductions in liver fat and liver enzymes. The drug also demonstrated statistically significant weight loss, with patients in the 1.2-mg and 1.8-mg dose groups losing 5% and 6.2% of their body weight at 24 weeks, respectively, compared to 1% in the placebo group.

Despite these positive outcomes, William Blair analysts remained unimpressed with the magnitude of weight loss, describing it as "non-differentiating" when compared to competitors like Eli Lilly's Mounjaro and Boehringer Ingelheim's survoditude, both of which have shown better weight loss profiles.

Market Reaction and Future Prospects

The market's reaction to the news was swift and severe, with Altimmune's stock closing at $3.61 on Thursday, representing a 53% drop from the previous day's closing price. While many investors and analysts view the results as a significant setback, not all outlooks are negative.

Analysts at H.C. Wainwright maintained a more optimistic stance, suggesting that the data "support advancement to Phase III and strengthen the case for pemvidutide as a potential best-in-class therapy." They argued that the sell-off in Altimmune shares was "overdone," indicating potential for recovery.

As the pharmaceutical industry continues to search for effective treatments for MASH, Altimmune's mixed results highlight the challenges and complexities involved in developing therapies for this condition. The company's next steps and the future of pemvidutide in the MASH treatment landscape remain uncertain, as stakeholders digest these latest clinical findings.