Novo Nordisk's semaglutide has demonstrated positive results in a Phase 3 trial for the treatment of metabolic dysfunction-associated steatohepatitis (MASH), paving the way for regulatory submissions in the US and Europe in early 2025. The ESSENCE trial results indicate that semaglutide, a GLP-1 receptor agonist, could become a significant therapy for this liver disease affecting millions.
ESSENCE Trial Results
The ESSENCE trial evaluated a once-weekly 2.4mg dose of semaglutide against a placebo in approximately 800 patients over 72 weeks. The study met its primary efficacy objectives, demonstrating that semaglutide was more effective than placebo in both resolving MASH and improving liver fibrosis. Specifically, 37% of patients treated with semaglutide experienced an improvement in liver fibrosis without worsening of steatohepatitis, compared to 22.5% in the placebo group. Furthermore, resolution of steatohepatitis without worsening of liver fibrosis was observed in 62.9% of semaglutide-treated patients versus 34.1% in the placebo group.
Comparison to Existing Therapies
Semaglutide's efficacy is being compared to Madrigal Pharma's Rezdiffra (resmetirom), the first FDA-approved therapy for MASH. In the MAESTRO-NASH trial for Rezdiffra, steatohepatitis resolution was achieved in 30% of patients on a 100mg dose, compared to 10% with placebo, after 52 weeks. While cross-trial comparisons should be interpreted cautiously, the data suggest semaglutide could offer a competitive treatment option.
Market Potential and Future Directions
MASH, a form of non-alcoholic fatty liver disease (NAFLD), affects an estimated 6 to 8 million people in the US and is closely linked to obesity and unhealthy lifestyles. The increasing prevalence of MASH in industrialized nations positions it as a substantial market opportunity, potentially worth billions of dollars globally. Approval for MASH would significantly expand semaglutide's market, which already includes Ozempic for diabetes and Wegovy for obesity.
Part 2 of the ESSENCE trial is an open-label extension that will continue to monitor patients for up to five years, focusing on endpoints such as cirrhosis-free survival. These long-term results, expected in 2029, will provide further insights into the durability and overall impact of semaglutide treatment.
Competition in the MASH Treatment Landscape
Other GLP-1-targeted drugs, such as Eli Lilly's tirzepatide and Boehringer Ingelheim's survodutide, have also shown promise in treating MASH. The potential availability of multiple treatment options in the coming years could intensify competition but also expand the market and improve patient outcomes through combination therapies.
