Altimmune announces results from IMPACT Phase 2b trial of pemvidutide

Altimmune (ALT) announced topline results from the IMPACT Phase 2b trial of pemvidutide in metabolic dysfunction-associated steatohepatitis. The Phase 2b trial enrolled 212 participants with biopsy-confirmed MASH and fibrosis stages F2/F3 with and without diabetes randomized 1:2:2 to receive either weekly subcutaneous pemvidutide at 1.2 mg or 1.8 mg doses or placebo for 24 weeks. Treatment discontinuation rates were low, with only 9% of participants prematurely discontinuing treatment. In an intent-to-treat analysis, in which participants with missing biopsies were considered non-responders, the proportions of participants achieving MASH resolution without worsening of fibrosis at 24 weeks were 59.1% and 52.1% for pemvidutide 1.2 mg and 1.8 mg, respectively versus 19.1% for placebo. The effects on fibrosis improvement without worsening of MASH in an ITT analysis were 31.8% and 34.5% for pemvidutide 1.2 mg and 1.8 mg, respectively compared with 25.9% for placebo. A supplemental AI-based analysis demonstrated statistically significant reductions in fibrosis, including 30.6% of participants receiving pemvidutide 1.8 mg achieving a 60% or more reduction in fibrosis compared to 8.2% receiving placebo. Statistically significant changes in well-established non-invasive tests of fibrosis, including Enhanced Liver Fibrosis score and Vibration-Controlled Transient Elastography were also observed compared with placebo at both doses. Together, these data suggest strong evidence of anti-fibrotic activity of pemvidutide in the MASH population. At 24 weeks, mean weight loss in pemvidutide-treated participants was 5.0% and 6.2% at the 1.2 mg and 1.8 mg doses, respectively, versus 1.0% in the placebo arm. Pemvidutide also demonstrated favorable safety and tolerability, with 0.0% and 1.2% adverse events related discontinuations in the pemvidutide 1.2 mg and 1.8 mg groups versus 2.4% in the placebo group, and there were no serious adverse events related to study medication. In an ITT analysis, MASH resolution without worsening of fibrosis was achieved in 59.1% and 52.1% of participants treated with pemvidutide 1.2 mg and 1.8 mg, respectively, vs. 19.1% of participants treated with placebo. In an additional ITT analysis, fibrosis improvement without worsening of MASH was achieved in 31.8% and 34.5% of participants treated with pemvidutide 1.2 mg and 1.8 mg vs. 25.9% of participants treated with placebo. A supplemental AI-based analysis demonstrated statistically significant reductions in fibrosis, which included 30.6% of participants receiving pemvidutide 1.8 mg achieving a 60% or more reduction in fibrosis compared to 8.2% receiving placebo. Pemvidutide-treated participants also achieved statistically significant reductions in non-invasive tests of fibrosis and inflammation. A total of 25.8% and 24.1% of participants receiving pemvidutide 1.2 mg and 1.8 mg, respectively, achieved the stringent endpoint of MASH resolution and fibrosis improvement versus 13.5% in participants receiving placebo. Participants receiving pemvidutide 1.2 mg and 1.8 mg achieved weight loss of 5.0% and 6.2% vs. 1.0% in placebo, with the trajectory showing no plateauing at 24 weeks. Liver fat reductions of 58.0% and 62.8% were achieved in participants who received pemvidutide 1.2 mg and 1.8 mg, respectively, vs. 16.2% in participants who received placebo. AEs leading to treatment discontinuation were 0.0% and 1.2% for pemvidutide 1.2 mg and 1.8 mg, respectively, vs. 2.4% in participants on placebo. No SAEs related to study drug or arrhythmias were reported at 24 weeks. Glycemic control was maintained with minimal changes in HbA1C regardless of diabetic status.