Altimmune eyes phase 3 MASH trial as weight loss deepens

 Altimmune has shared an update on the metabolic dysfunction-associated steatohepatitis (MASH) study that sank its stock in June. The 48-week readout linked the top dose of the GLP-1/glucagon dual receptor agonist to continued weight loss and improvements on noninvasive measures of liver fibrosis.

Maryland-based Altimmune published 24-week data from the phase 2 trial in June. Pemvidutide failed to beat placebo on an endpoint that tracked patients who had improved fibrosis without worsening MASH, contributing to a steep drop in Altimmune’s share price. With no biopsies taken at Week 48, Altimmune is reliant on noninvasive measures of fibrosis to try to change the narrative around pemvidutide.

Between the two readouts, enhanced liver fibrosis (ELF) scores on the high dose improved from -0.5 to -0.58. However, patients on the lower dose gave up some of their earlier gains, with ELF scores changing from -0.6 at Week 24 to -0.49 at Week 48. Both doses were significantly better than placebo at Week 48.

Altimmune also shared liver stiffness measurement (LSM) data, reporting mean reductions from baseline of 3.04 and 3.97, respectively, on the low and high doses. Mazen Noureddin, M.D., principal investigator for the study, said in a statement that the ELF and LSM results are particularly compelling because the 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,” Noureddin said. 

Noureddin added that he is encouraged by the dose response, which was evident in the weight loss data. Patients on the low dose largely maintained the weight lost by Week 24, with the figure falling from 5% to 4.5% over the following 24 weeks. But people on the high dose continued to shed the pounds, with weight loss increasing from 6.2% to 7.5% between the two readouts and yet to plateau. 

Yet, in other areas, even the high dose gave up some of the earlier gains. The reduction in liver fat content was lower at both doses at Week 48 than at Week 24. After 24 weeks, Altimmune saw reductions of 58% and 62.8%, respectively, on the low and high doses. The figures after 48 weeks were 45.2% for the low dose and 54.7% on the high dose. 

Safety and tolerability remained a bright spot in the Week 48 data. Adverse events leading to treatment discontinuation occurred in 0% and 1.2%, respectively, of patients on the low and high doses, compared to 3.5% of their peers on placebo.

Shares in Altimmune slipped slightly, after initially rising, in premarket trading as investors digested the data. While investors appear to have doubts, Altimmune is projecting confidence as it prepares for talks with the FDA about a phase 3 trial it plans to start next year.

The biotech highlighted the FDA’s recent qualification of a MASH artificial intelligence tool as a positive for its phase 3 program. Altimmune plans to integrate the tool into the trial to help standardize histologic assessment and reduce the time and resources needed for MASH drug development. The biotech ended September with $211 million.  

https://www.fiercebiotech.com/biotech/altimmune-eyes-phase-3-mash-trial-weight-loss-deepens