Novo Nordisk's Wegovy (semaglutide) 2.4 mg has shown promising results in treating metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver fibrosis. The Phase III ESSENCE trial revealed that Wegovy was significantly more effective than placebo in improving liver histology. These findings offer hope for a condition affecting millions worldwide, with prevalence expected to surge in the coming years.
The ESSENCE trial, a two-part study, involved 1,200 patients randomized to receive either Wegovy 2.4 mg or placebo, in addition to standard care, over 240 weeks. Part one of the trial assessed the impact of Wegovy on liver histology after 72 weeks, while part two is designed to evaluate the drug's ability to reduce the risk of liver-related clinical events over 240 weeks; results for part two are expected in 2029.
Key Findings at 72 Weeks
At the 72-week mark, 37% of patients treated with Wegovy exhibited improvement in liver fibrosis without any worsening of steatohepatitis, compared to just 22.5% in the placebo group. Furthermore, 62.9% of patients on Wegovy achieved resolution of steatohepatitis without worsening of liver fibrosis, versus 34.1% on placebo.
"We are very pleased about the ESSENCE clinical trial results and the potential of semaglutide to help people living with MASH,” said Martin Holst Lange, EVP, head of development, Novo Nordisk, in a press release. He also noted that MASH affects one in three people with overweight or obesity, highlighting the significant unmet need.
Safety and Tolerability
The safety profile of Wegovy in the ESSENCE trial was consistent with previous studies, indicating that the drug is generally well-tolerated. Common adverse effects included nausea, diarrhea, vomiting, constipation, stomach pain, and headache.
MASH: A Growing Concern
Over 250 million people worldwide are estimated to have MASH, and this number is projected to increase significantly. Experts predict that the prevalence of MASH will rise by 63% by 2030, potentially making it the leading cause of liver transplants in the United States as early as next year. Currently, it is estimated that 1.5% to 6.5% of adults in the United States have MASH.
Addressing Stigma and Improving Awareness
Lorraine Stiehl, CEO of the American Liver Foundation, emphasized the importance of the recent name change from NASH to MASH. "Patients, providers, scientists, non-profits, and advocates in the worldwide liver community came together last year to modify the way we talk about NASH—now MASH—in an effort to better identify who has the disease or is at risk for the disease," said Stiehl. She added that the name change aims to reduce stigma associated with the terms 'fatty' and 'alcoholic,' which can hinder screening, diagnosis, and treatment.
Regulatory Plans
Novo Nordisk intends to file for regulatory approval of Wegovy for the treatment of MASH in both the United States and Europe by mid-2025. These submissions could pave the way for a new treatment option for a disease with limited therapeutic interventions.
