Results from part 1 of the ongoing Phase 3 ESSENCE trial - evaluating the effect of once-weekly subcutaneous semaglutide 2.4mg on liver tissue (histology) compared with placebo in people with metabolic dysfunction-associated steatohepatitis (MASH) and moderate to advanced liver fibrosis (stage 2 or 3) - showed that at Week 72, primary endpoints showed 62.9% of people treated with semaglutide 2.4mg achieved resolution of steatohepatitis with no worsening of liver fibrosis compared to 34.1% on placebo.
The results, presented at the 75th American Association for the Study of Liver Diseases (AASLD), also revealed 37% of people treated with semaglutide 2.4mg achieved improvements in liver fibrosis with no worsening of steatohepatitis compared to 22.5% on placebo. Overall, secondary endpoints showed 32.8% of patients treated with semaglutide 2.4 mg achieved both resolution of steatohepatitis with improvements in liver fibrosis (as compared to 16.2% of patients on placebo).
"These initial data shared at The Liver Meeting demonstrated that semaglutide 2.4mg slowed MASH progression and reversed existing liver damage," said Dr Arun Sanyal, principal investigator of the study, and Director, Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University. "The ESSENCE data may represent key findings for patients in the treatment of MASH, which is estimated to affect about one in 20 adults in the US."
In addition to meeting both primary endpoints, secondary endpoints showed histological benefits were reflected in improvements of pre-specified non-invasive tests (NITs) in people treated with semaglutide 2.4mg vs placebo. The additional data showed improvements in liver enzymes (including ALT, AST, and GGT), as well as the Enhanced Liver Fibrosis (ELF) test. In the trial, semaglutide 2.4mg appeared to have a safety profile similar to previous semaglutide 2.4mg trials in other therapeutic area patient populations.
Semaglutide 2.4mg is not approved in the US to treat MASH. Novo Nordisk expects to file for regulatory approvals in the US in the first half of 2025.
ESSENCE is a Phase 3 trial evaluating the effect of once-weekly subcutaneous semaglutide 2.4mg in adults with metabolic dysfunction-associated steatohepatitis with moderate to advanced liver fibrosis (stage 2 or 3). It is a two-part trial where 1,200 planned participants were randomized 2:1 to receive semaglutide 2.4mg or placebo, on top of standard of care for 240 weeks. In part 1, the objective was to demonstrate that treatment with semaglutide 2.4mg improves liver histology at 72 weeks based on biopsy sampling from the first 800 randomised patients. In part 2, the objective is to demonstrate that treatment with semaglutide 2.4mg lowers the risk of liver-related clinical events compared to placebo in adults with MASH and moderate to advanced liver fibrosis at 240 weeks.
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