Altimmune's GLP-1/Glucagon Agonist Shows Mixed Results in Phase 2 MASH Trial

Altimmune's pemvidutide, a GLP-1/glucagon dual receptor agonist, has demonstrated a mix of promise and setbacks in a recent phase 2 trial for metabolic dysfunction-associated steatohepatitis (MASH). The study results, while highlighting the drug's potential in weight loss, have led to a significant drop in the company's stock price.

Trial Outcomes: A Hit and a Miss

The phase 2 trial, which enrolled 212 MASH patients, evaluated weekly subcutaneous doses of pemvidutide at 1.2 mg and 1.8 mg against a placebo. The study achieved one of its primary endpoints, with 59.1% of the 1.2-mg cohort and 52.1% of the 1.8-mg cohort experiencing MASH resolution without worsening fibrosis, compared to 19.1% in the placebo group.

However, pemvidutide failed to demonstrate a statistically significant difference in improving fibrosis without worsening MASH, the trial's other key endpoint. The 1.2-mg and 1.8-mg cohorts saw 31.8% and 34.5% of patients achieve this goal, respectively, compared to 25.9% in the placebo group.

Despite this setback, Altimmune emphasized that 30.6% of patients on the 1.8 mg dose experienced a 60% or greater reduction in fibrosis, compared to 8.2% in the placebo group. The company views these data as "strong evidence of anti-fibrotic activity of pemvidutide in the MASH population."

Weight Loss Potential and Market Implications

In the increasingly competitive obesity treatment landscape, pemvidutide showed promising results. The 1.2-mg and 1.8-mg cohorts demonstrated mean weight losses of 5% and 6.2%, respectively, compared to 1% for placebo. Notably, the weight loss trajectory showed no signs of plateauing at 24 weeks.

These findings build on previous phase 2 obesity trial results, which linked pemvidutide to a mean weight loss of 15.6% after 48 weeks, with most of the weight lost coming from fat rather than muscle. This positions Altimmune's drug as a potential contender in the burgeoning GLP-1 market for obesity and MASH treatment.

The mixed results, however, have had a significant impact on investor confidence. Altimmune's stock plummeted 59% in premarket trading following the announcement, dropping from $7.71 to $3.18.

Industry Context and Future Outlook

The MASH treatment landscape is evolving rapidly, with several pharmaceutical companies making strides in this historically challenging area. Novo Nordisk is awaiting an FDA decision on semaglutide for MASH treatment, while Eli Lilly's tirzepatide and Boehringer Ingelheim's survodutide have also shown promise in addressing the condition.

Altimmune remains optimistic about pemvidutide's future, with plans for an end-of-phase 2 meeting with the FDA in the fourth quarter of 2025. The company aims to progress rapidly to phase 3 trials, banking on the drug's demonstrated efficacy in MASH resolution and weight loss, coupled with its favorable tolerability profile.

As the pharmaceutical industry continues to explore dual-agonist approaches in obesity and liver health therapeutics, pemvidutide's unique GLP-1/glucagon mechanism may offer advantages in addressing both weight loss and liver health. However, the path forward will depend on further clinical validation and regulatory discussions in the coming months.