Altimmune says pemvidutide met 48-week liver markers in Phase 2b MASH trial

On December 19, 2025, Altimmune reported that its investigational drug pemvidutide met key 48-week measures in the Phase 2b IMPACT trial in people with metabolic dysfunction-associated steatohepatitis (MASH), with statistically significant improvements in non-invasive liver tests compared with placebo ^[1].

The trial enrolled 212 people with biopsy-confirmed MASH and fibrosis stages F2 or F3, with and without diabetes. Participants were randomly assigned in a 1:2:2 ratio to weekly under-the-skin injections of pemvidutide 1.2 mg, pemvidutide 1.8 mg, or placebo for 48 weeks ^[1]. The company's primary efficacy endpoints — MASH resolution without worsening of fibrosis, or fibrosis improvement without worsening of MASH — were measured at 24 weeks. The 48-week results announced here cover non-invasive tests rather than repeat biopsies ^[1].

On the Enhanced Liver Fibrosis (ELF) test, the 1.2 mg and 1.8 mg doses produced mean reductions from baseline of 0.49 and 0.58, compared with a mean increase of 0.16 in placebo-treated participants (p<0.0001 for both doses). Liver Stiffness Measurement (LSM) fell by a mean of 3.04 with 1.2 mg (p<0.05) and 3.97 with 1.8 mg (p<0.001), versus 0.03 with placebo. The share of participants who reached both a reduction of at least 0.5 in ELF and a 30% reduction in LSM was 27.8% at 1.2 mg (p<0.001) and 32.4% at 1.8 mg (p<0.0001), versus 3.2% on placebo ^[1]. The company said the improvements continued from the 24-week timepoint ^[1].

Pemvidutide-treated participants also had larger reductions in other non-invasive measures. Liver fat content fell by a mean of 45.2% at 1.2 mg and 54.7% at 1.8 mg, versus 8.2% on placebo (p<0.0001). Alanine aminotransferase (ALT) fell by 37.8 IU/L and 37.4 IU/L, versus 10.3 IU/L on placebo (p<0.0001 for both). Corrected T1 (cT1) fell by 124 and 140 milliseconds, versus 21 ms on placebo (p<0.0001 for both) ^[1].

Weight loss averaged 4.5% at 1.2 mg and 7.5% at 1.8 mg, compared with 0.2% on placebo (p<0.0001 for both). The company said weight loss with the 1.8 mg dose was still continuing at 48 weeks, with no evidence of a plateau ^[1].

Adverse events that led to discontinuation occurred in 0% of the 1.2 mg group and 1.2% of the 1.8 mg group, compared with 3.5% of placebo participants. No serious or severe adverse events related to treatment were reported, according to the company ^[1].

Altimmune also said it held an End-of-Phase 2 meeting with the U.S. Food and Drug Administration and reached alignment on parameters for a registrational Phase 3 trial in MASH patients with moderate to advanced liver fibrosis. The FDA recently qualified an artificial intelligence tool, AIM-MASH AI Assist, and the agency was open to integrating it into the Phase 3 trial to help standardize histologic assessment ^[1].

Why it matters for patients

Pemvidutide is not approved and is not a GLP-1 medicine on its own. It is an investigational peptide designed to activate both glucagon and GLP-1 receptors in a balanced 1:1 ratio. The glucagon activity is intended to act directly on the liver, while the GLP-1 activity drives appetite suppression and weight loss ^[1]. People taking semaglutide (Ozempic, Wegovy, Rybelsus) or tirzepatide (Mounjaro, Zepbound) cannot get pemvidutide today, and this announcement does not include any comparison between pemvidutide and those medicines.

The results come from 212 people in a mid-stage trial, and they rest on blood tests and imaging rather than follow-up liver biopsies. The company describes ELF and LSM as well-established markers of fibrosis and liver inflammation that are strongly associated with histological changes and liver-related events ^[1], but whether the marker improvements translate into fewer cases of cirrhosis, liver failure or liver cancer has not been reported. MASH is a progressive disease that can lead to cirrhosis, liver failure or liver cancer and is a common reason for liver transplantation in the U.S.; management relies largely on lifestyle changes, and the company says currently approved treatments may not fully address both the metabolic drivers and the fibrosis ^[1].

The tolerability figures matter because nausea, vomiting and similar side effects are a common reason people stop GLP-1-based therapies. In this trial, the discontinuation rate for adverse events was lower in both pemvidutide groups than on placebo, though researchers were not blinded to which group they were in from the participants' perspective — the study was described as double-blind ^[1].

What happens next

Altimmune said it intends to begin a Phase 3 program in 2026 ^[1]. No specific start date, size, duration or cost has been disclosed. The FDA granted pemvidutide Fast Track designations for MASH and for alcohol use disorder, which is meant to speed review but does not guarantee approval ^[1]. Separate Phase 2 trials in alcohol use disorder (RECLAIM) and alcohol-associated liver disease (RESTORE) began in May 2025 and July 2025 and are ongoing ^[1]. It has not been reported when 48-week biopsy-based histology results from IMPACT will be available.