Altimmune's pemvidutide hits key 48-week endpoints in the Phase 2b IMPACT MASH trial

Altimmune said its experimental drug pemvidutide met key goals in a mid-stage trial for metabolic dysfunction-associated steatohepatitis, or MASH, after 48 weeks of treatment ^[1]. The company reported statistically significant improvements in blood and imaging tests that track liver scarring, along with continued weight loss and a low rate of people stopping treatment because of side effects ^[1].

The Phase 2b trial, called IMPACT, enrolled 212 people with biopsy-confirmed MASH and moderate to advanced liver fibrosis, randomly assigning them to weekly injections of pemvidutide at 1.2 mg, 1.8 mg, or a placebo for 48 weeks ^[1]. Pemvidutide is a "balanced" dual agonist that activates both glucagon and GLP-1 receptors in a 1:1 ratio, a design intended to target liver fat and inflammation through the glucagon pathway while also driving weight loss through the GLP-1 pathway ^[1].

On a liver stiffness test called LSM, the 1.2 mg dose reduced scores by 3.04 points and the 1.8 mg dose by 3.97 points, compared with a 0.03-point drop on placebo ^[1]. On the ELF blood test for fibrosis, the 1.2 mg and 1.8 mg doses cut scores by 0.49 and 0.58 points, respectively, versus a 0.16-point increase for placebo ^[1]. Both differences were statistically significant, with p-values below 0.05 for LSM and below 0.0001 for ELF ^[1]. Liver fat content fell 45.2% and 54.7% at the two doses, compared with 8.2% for placebo, and liver enzyme ALT dropped by roughly 37 points at both doses versus about 10 points on placebo ^[1].

Weight loss reached 4.5% on the 1.2 mg dose and 7.5% on the 1.8 mg dose by week 48, compared with 0.2% for placebo, and the company said the 1.8 mg group had not plateaued, meaning weight loss was still continuing at that point ^[1]. Side effects leading people to quit the trial were rare: 0% on the 1.2 mg dose, 1.2% on the 1.8 mg dose, and 3.5% on placebo, and no serious or severe treatment-related adverse events were reported ^[1]. Altimmune also said it met with the FDA and reached agreement on the design for a registrational Phase 3 trial in MASH patients with moderate to advanced fibrosis, which it plans to start in 2026 ^[1].

Why it matters for patients

MASH is a liver disease in which fat buildup and inflammation can progress to scarring, cirrhosis, liver failure, or cancer, and it is one of the leading causes of liver transplants in the U.S. ^[1]. Right now, treatment mostly relies on lifestyle changes, and existing options may not fully address both the metabolic causes and the fibrosis itself ^[1]. If pemvidutide's results hold up in larger trials, it could offer people with this progressive disease a drug that targets liver scarring directly rather than only weight or blood sugar.

It's important to note these are non-invasive test results, not liver biopsy findings, though the company and an outside investigator said tests like ELF and LSM are strongly linked to biopsy-confirmed fibrosis changes ^[1]. The trial's original primary goal, measured at 24 weeks, was based on biopsy results showing MASH resolution or fibrosis improvement, and that data was reported separately from this 48-week release ^[1]. This announcement is Altimmune's own topline summary, and it has not yet been published in a peer-reviewed journal or reviewed line-by-line by the FDA for approval.

What happens next

Altimmune said it plans to launch a Phase 3 trial of pemvidutide in MASH patients with moderate to advanced liver fibrosis sometime in 2026, following the recent end-of-Phase 2 meeting with the FDA ^[1]. The company is also running separate mid-stage trials of pemvidutide for alcohol use disorder and alcohol-associated liver disease, which started in May and July 2025 ^[1]. Pemvidutide remains investigational and is not approved for any use in the United States.