Novo Nordisk's semaglutide 2.4mg has demonstrated statistically significant and superior improvement in both liver fibrosis and resolution of metabolic dysfunction-associated steatohepatitis (MASH) compared to placebo in the Phase 3 ESSENCE trial. The trial, involving adults with stage 2 or stage 3 liver fibrosis, met its primary endpoint after 72 weeks of treatment. These findings highlight the potential of semaglutide to address a significant unmet need in individuals with MASH.
Key Findings from the ESSENCE Trial
The ESSENCE trial's topline data revealed that 37.0% of participants treated with semaglutide 2.4mg achieved improvement in liver fibrosis with no worsening of steatohepatitis, compared to 22.5% in the placebo group. Furthermore, 62.9% of semaglutide-treated participants experienced resolution of steatohepatitis without worsening of liver fibrosis, versus only 34.1% in the placebo group. The safety and tolerability profiles of semaglutide 2.4mg were consistent with previous trials.
Management Perspective
Martin Holst Lange, Executive Vice President and Head of Development at Novo Nordisk, expressed enthusiasm about the results, stating, “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.”
MASH Disease Burden and Unmet Needs
MASH is a progressive metabolic liver disease that can be fatal if not effectively managed. In the US, the number of MASH cases is projected to increase by 63% between 2015 and 2030, rising from 16.5 million to 27.0 million. MASH is closely linked to cardiovascular, renal, and other metabolic diseases. It is estimated that one in three adults with obesity also have MASH, many of whom remain undiagnosed due to its asymptomatic nature.
Trial Design and Future Steps
The ESSENCE trial is a two-part clinical trial involving 1200 participants with MASH and moderate-to-advanced liver fibrosis, randomized 2:1 to semaglutide 2.4mg or placebo, in addition to standard of care, over 240 weeks. Part 1 focused on demonstrating improved liver histology based on biopsy evaluation at 72 weeks for the first 800 participants. Part 2 is an open-label extension monitoring endpoints including cirrhosis-free survival for up to 5 years, with results expected in 2029. Novo Nordisk anticipates submitting regulatory applications in the US and Europe in the first half of 2025. Detailed results from part 1 will be presented at an upcoming scientific conference this year.
About Semaglutide
Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist. It is approved in the US as an adjunct to diet and exercise for managing hyperglycemia in type 2 diabetes (Ozempic) and for chronic weight management in obesity or overweight individuals with related comorbidities (Wegovy). It has also received label extensions for cardiovascular risk reduction in specific high-risk patient populations.
