Altimmune has announced positive topline results from the IMPACT Phase IIb trial of pemvidutide, a balanced 1:1 glucagon/GLP-1 dual receptor agonist, in patients suffering with metabolic dysfunction-associated steatohepatitis (MASH).

The trial demonstrated statistically significant improvements in key non-invasive tests (NITs), such as Liver Stiffness Measurement (LSM) and Enhanced Liver Fibrosis (ELF), versus placebo over 48 weeks.

The data showed continued reductions from 24 weeks and indicated ongoing antifibrotic activity for both doses (1.2mg and 1.8mg).

The results indicated that pemvidutide achieved significant reductions in primary non-invasive markers of fibrosis. For ELF, 1.2 mg and 1.8 mg doses showed mean reductions of -0.49 and -0.58, respectively, compared to a +0.16 increase in placebo-treated patients. For LSM, mean reductions were -3.04 and -3.97 for the two doses, respectively, against -0.03 for placebo-treated patients.

The proportion of participants achieving both a ≥0.5 reduction in ELF and a 30% reduction in LSM was 27.8% and 32.4% for 1.2 mg and 1.8 mg doses, respectively, compared to 3.2% for placebo.

Statistically significant reductions were also observed in important non-invasive measures of liver health and hepatic inflammation including corrected T1 (cT1), liver fat content, and alanine aminotransferase (ALT).

Weight loss of 4.5% and 7.5% was recorded for the 1.2 mg and 1.8 mg doses, respectively, compared to 0.2% for placebo. The 1.8mg dose showed no evidence of plateauing at 48 weeks.

Discontinuations due to adverse events occurred in 0% and 1.2% of pemvidutide-treated participants, compared to 3.5% in the placebo group, with no reported serious or severe treatment-related adverse events.

IMPACT trial principal investigator Mazen Noureddin said: “The magnitude of response versus placebo on measures such as ELF and LSM at 48 weeks makes these data particularly compelling, as these noninvasive markers have been shown to correlate with histologic fibrosis stage.

“These results reinforce that pemvidutide may address both liver-specific and metabolic drivers of MASH without compromising tolerability – three critical elements of a potential effective treatment for this patient population. I am encouraged by the dose response observed and the performance of the 1.8 mg arm and I am eager to see this differentiated therapeutic candidate advance into Phase III evaluation.”

Altimmune also announced that it held an End-of-Phase II meeting with the Food and Drug Administration (FDA), leading to alignment on the parameters required for a registrational Phase III trial of pemvidutide in MASH patients suffering with moderate to advanced liver fibrosis.

Following the FDA’s recent qualification of AIM-MASH AI Assist, the regulatory body expressed openness to Altimmune’s plan to incorporate this AI tool into the Phase 3 trial.

AIM-MASH AI Assist is stated to be designed to standardise histologic assessments and cut down the time and resources required for the MASH drug development process.

Altimmune CEO Vipin Garg said: “With the benefit of FDA feedback and these 48-week data now in hand, we are greatly looking forward to progressing pemvidutide to a Phase 3 program which we intend to initiate in 2026.

“Strong evidence of antifibrotic improvements based upon non-invasive tests, combined with an attractive tolerability profile, highlight pemvidutide’s differentiation and potential to be a meaningful treatment option for the MASH patient community.”

In September 2023, Altimmune completed dosing the last subject in its Phase II MOMENTUM clinical trial of pemvidutide for the treatment of obesity or overweight.