Altimmune has released updated 48-week results from its phase 2 trial of pemvidutide, a GLP-1/glucagon dual receptor agonist being developed for metabolic dysfunction-associated steatohepatitis (MASH), demonstrating continued weight loss and sustained improvements in liver fibrosis markers that could support the company’s planned phase 3 program.
The updated data comes nearly six months after disappointing 24-week results that triggered a sharp decline in Altimmune’s stock price, as reported by Fierce Biotech. The earlier readout failed to meet its primary endpoint, improvement in fibrosis without worsening MASH, raising questions about the drug’s efficacy. The new 48-week findings aim to tell a more encouraging story, though with important nuances.
Weight loss emerged as a particularly strong benefit. Patients receiving the high dose of pemvidutide showed accelerating weight reduction between the 24- and 48-week marks, with weight loss increasing from 6.2% to 7.5% and showing no signs of plateauing. In contrast, patients on the lower dose largely maintained their earlier weight loss but showed minimal additional improvement, declining from 5% to 4.5% between timepoints. This dose-response pattern suggests the higher dose provides ongoing metabolic benefit.
Liver fibrosis markers also demonstrated improvements, though with mixed results. Enhanced liver fibrosis (ELF) scores, noninvasive markers that correlate with histologic fibrosis stages, improved on the high dose from -0.5 to -0.58, while the low dose plateaued at -0.49. Liver stiffness measurements showed mean reductions from baseline of 3.04 and 3.97 for low and high doses, respectively. Study principal investigator Dr. Mazen Noureddin emphasized the significance of these noninvasive markers, stating they correlate with actual histologic fibrosis stage, making them clinically meaningful indicators of liver health.
However, liver fat content reduction presented a concerning trend. Both doses showed lower reductions at Week 48 compared to Week 24, dropping from 58% to 45.2% on the low dose and from 62.8% to 54.7% on the high dose. This reversal suggests the drug’s effect on hepatic steatosis may not be durable, though fat reduction remained substantially better than placebo.
Safety and tolerability remained a bright spot. Adverse events leading to treatment discontinuation occurred in only 0% and 1.2% of patients on low and high doses, respectively, compared to 3.5% on placebo, indicating pemvidutide is well-tolerated overall.
Despite positive elements, investor reaction was cautious, with Altimmune’s stock initially rising then slipping in premarket trading as investors weighed the mixed data. Nevertheless, the company is moving forward confidently, preparing for FDA discussions about launching a phase 3 trial next year.
Altimmune highlighted a favorable development for its planned trial: the FDA recently qualified a new artificial intelligence tool for MASH assessment. The company intends to integrate this tool into its phase 3 program to standardize histologic evaluation and reduce development timelines and costs, a potentially significant advantage in the competitive MASH space.
