Semaglutide Shows Promise in MASH Treatment, Phase III Trial Results
Key Insights
Semaglutide significantly improved liver fibrosis and MASH (search) resolution compared to placebo in a Phase III trial, marking a potential breakthrough in treatment.
The ESSENCE trial demonstrated that semaglutide led to higher rates of steatohepatitis resolution without worsening fibrosis (63% vs 34%) and fibrosis improvement (37% vs 23%).
Patients on semaglutide achieved a dual secondary endpoint of both MASH (search) resolution and liver fibrosis improvement at twice the rate of those on placebo (33% vs 16%).
Semaglutide (Wegovy) has demonstrated significant efficacy in treating metabolic dysfunction-associated steatohepatitis (MASH (search)), according to interim results from a Phase III trial. The study, known as ESSENCE, revealed that semaglutide not only improved liver fibrosis but also led to greater rates of MASH resolution compared to placebo.
Key Findings from the ESSENCE Trial
Philip Newsome, PhD, of King's College Hospital in London, presented the findings at the annual meeting of the American Association for the Study of Liver Diseases. The data showed that after 72 weeks, 63% of patients treated with semaglutide experienced steatohepatitis resolution without worsening of liver fibrosis, compared to only 34% in the placebo group (P < 0.0001). Additionally, 37% of semaglutide-treated patients showed improvement in liver fibrosis without worsening of steatohepatitis, versus 23% in the placebo group (P < 0.0001).
Notably, twice as many patients on semaglutide achieved both MASH (search) resolution and liver fibrosis improvement (33% vs 16%, P < 0.0001). Patients also experienced an average body weight reduction of 11% with semaglutide, compared to 2% with placebo.
Detailed Study Design and Patient Population
The ESSENCE trial is a double-blind, multicenter Phase III study involving 1,200 adults with biopsy-confirmed MASH (search) and stage 2 or 3 liver fibrosis. Participants were randomized in a 2:1 ratio to receive either once-weekly subcutaneous semaglutide at a dose of 2.4 mg or a matching placebo for 240 weeks. The primary endpoints for the initial phase of the trial focused on steatohepatitis resolution without worsening of liver fibrosis and improvement in liver fibrosis without worsening of steatohepatitis at week 72.
Eligibility criteria included a non-alcoholic fatty liver disease (NAFLD (search)) activity score of 4 or higher. Exclusion criteria encompassed other chronic liver diseases, excessive alcohol use, prior use of GLP-1 receptor (search) agonists, and unstable use of glucose-lowering, lipid-lowering, or weight-loss medications.
The interim analysis included the first 800 participants who completed 72 weeks of treatment. The mean age of these patients was approximately 55 years, with a majority being women. About 55% had type 2 diabetes, the mean body mass index ranged from 34 to 35, and over two-thirds had stage 3 liver fibrosis.
Impact on Cardiometabolic Parameters and Safety Profile
In addition to the primary efficacy endpoints, semaglutide treatment led to improvements in liver enzymes (alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase), liver stiffness (measured by vibration-controlled transient elastography), and cardiometabolic risk parameters, including blood pressure, glycemic control, dyslipidemia, and C-reactive protein levels.
The safety profile of semaglutide was consistent with previous studies. Adverse events were reported in 86% of the semaglutide group and 80% of the placebo group, with nausea, diarrhea, constipation, vomiting, and decreased appetite being the most common. Serious adverse events occurred in 13% of each group, and fatal adverse events were rare (0.4% in the semaglutide group and 1.5% in the placebo group).
Implications for MASH Treatment
These results are particularly significant given the limited treatment options currently available for MASH (search). As Philip Newsome stated, it is a landmark achievement to report the first GLP-1 receptor (search) agonist to demonstrate efficacy in a Phase III trial for MASH. The findings suggest that semaglutide could become a valuable tool in managing this progressive liver disease.
Novo Nordisk, the manufacturer of semaglutide, has announced plans to seek regulatory approval for the drug in MASH (search) based on these results. The ongoing Phase III trial will continue to evaluate semaglutide's long-term effects on cirrhosis-free survival.