Novo Nordisk's semaglutide, the active ingredient in its popular weight loss medication, has shown positive results in a Phase 3 trial for metabolic dysfunction-associated steatohepatitis (MASH). The company announced it will seek regulatory approval in both the U.S. and Europe in the first half of 2025, potentially making semaglutide one of the first drugs approved for this liver condition.
The Phase 3 trial evaluated semaglutide in individuals with MASH, a condition affecting millions and a leading cause of liver transplants. The study met its primary endpoints, demonstrating statistically significant improvements in key markers of the disease.
Key Trial Results
After 72 weeks of treatment, 37% of participants receiving semaglutide and standard therapy experienced an improvement in liver scarring (fibrosis) without worsening of their MASH, compared to 22.5% in the placebo group. Furthermore, 63% of those on semaglutide saw their MASH resolve without any worsening of liver scarring, versus 34% in the placebo group.
Novo Nordisk reported that semaglutide exhibited a safety profile consistent with previous trials, suggesting it is well-tolerated by patients. Detailed study results, including secondary endpoint data and adverse event information, are expected to be presented at an upcoming medical meeting later in 2024. The trial's second phase is ongoing and will assess semaglutide's long-term ability to prevent cirrhosis, a severe complication of MASH.
Implications for MASH Treatment
Martin Holst Lange, Novo Nordisk’s head of development, emphasized the significant unmet need in MASH treatment, noting that one in three people with overweight or obesity also live with MASH, which seriously impacts their health. The potential approval of semaglutide could provide a valuable new option for these patients.
MASH is characterized by a buildup of fat in the liver, often associated with metabolic disorders like diabetes. While it has been a target for drug development, many previous attempts have failed. Madrigal Pharmaceuticals' Rezdiffra recently gained approval for MASH. Other companies like Akero Therapeutics and 89bio are also developing potential treatments.
Competitive Landscape
GLP-1 drugs like semaglutide are emerging as potential treatments for MASH due to their effects on weight loss and metabolic health. Eli Lilly and Boehringer Ingelheim are also exploring GLP-1-based therapies for MASH. However, some analysts believe that semaglutide's results, while positive, may not represent a "silver bullet" for MASH, suggesting that a combination of therapies may be necessary. According to Leerink Partners’ Thomas Smith, MASH will become “a polypharmacy opportunity with room for multiple liver-directed mechanisms and treatment approaches.”
Analysts from William Blair and RBC Capital Markets noted that the magnitude of semaglutide's effect on fibrosis was similar to that of Rezdiffra and potentially less than what has been observed with drugs from 89bio and Akero, although cross-trial comparisons should be interpreted cautiously.
