Novo Nordisk's semaglutide 2.4mg has shown positive results in the treatment of metabolic dysfunction-associated steatohepatitis (MASH) and moderate to advanced liver fibrosis. The Phase III ESSENCE trial met its primary endpoints, demonstrating a significant improvement in liver fibrosis compared to placebo.
The double-blinded, 240-week study involved 1,200 adults with MASH and stage two or three liver fibrosis. During the first part of the trial, the effects of semaglutide on liver tissue were assessed in 800 participants over 72 weeks. Semaglutide 2.4mg, a glucagon-like peptide 1 (GLP-1) receptor agonist known as Wegovy, was administered subcutaneously once weekly.
Key Findings from the ESSENCE Trial
The trial revealed that 37% of participants treated with semaglutide experienced an improvement in liver fibrosis without steatohepatitis worsening at 72 weeks, compared to 22.5% in the placebo group. Additionally, 62.9% of participants in the semaglutide group achieved resolution of steatohepatitis without any worsening of liver fibrosis, versus 34.1% in the placebo group.
The safety and tolerability profile of semaglutide 2.4mg was consistent with previous trials, reinforcing its potential as a viable treatment option for MASH.
Regulatory Plans and Future Outlook
Novo Nordisk plans to seek regulatory approvals in the US and European Union (EU) in the first half of next year. The second part of the ESSENCE trial is ongoing, with results expected in 2029.
Martin Holst Lange, Executive Vice President and Head of Development at Novo Nordisk, stated, "We are very pleased about the ESSENCE clinical trial results and the potential of semaglutide to help people living with MASH... Among people with overweight or obesity, one in three live with MASH. This has a serious impact on their health and represents a significant unmet need."
Context of MASH and Semaglutide
MASH is a severe and progressive liver disease associated with metabolic disorders. Semaglutide (Wegovy) is already approved for use alongside a reduced-calorie diet and increased physical activity to reduce the risk of major adverse cardiovascular events (MACE) in adults with cardiovascular disease and obesity or those deemed overweight in the US.
Novo Nordisk also plans to file for a label expansion for its oral semaglutide, Rybelsus, in the US and EU, following positive outcomes from the Phase III SOUL trial.
