Novo Nordisk's semaglutide 2.4 mg has shown promising results in treating metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis. The headline results from part 1 of the ESSENCE trial, a pivotal phase 3 study, indicate that the drug leads to superior improvement in liver fibrosis and MASH resolution compared to placebo.
The ESSENCE trial is a 240-week, double-blinded study involving 1,200 adults with MASH and moderate to advanced liver fibrosis (stage 2 or 3). Part 1 of the trial focused on the first 800 randomized participants over 72 weeks, evaluating the impact of once-weekly semaglutide 2.4 mg on liver tissue histology compared to placebo, both on top of standard of care.
The trial met its primary endpoints, demonstrating a statistically significant improvement in liver fibrosis without worsening of steatohepatitis, as well as resolution of steatohepatitis without worsening of liver fibrosis. Specifically, 37.0% of patients treated with semaglutide 2.4 mg achieved improvement in liver fibrosis without worsening of steatohepatitis, compared to 22.5% in the placebo group. Furthermore, 62.9% of patients on semaglutide 2.4 mg achieved resolution of steatohepatitis without worsening of liver fibrosis, versus 34.1% on placebo.
Safety and Tolerability
The safety profile of semaglutide 2.4 mg in the ESSENCE trial was consistent with previous trials, indicating that the drug is generally safe and well-tolerated.
Management Perspective
"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, executive vice president and head of Development at Novo Nordisk. He also noted the significant unmet need, stating that "Among people with overweight or obesity, one in three live with MASH. This has a serious impact on their health."
Regulatory Plans and Future Steps
Novo Nordisk anticipates filing for regulatory approvals in the US and EU in the first half of 2025. Detailed results from the ESSENCE trial will be presented at a scientific conference later in 2024. Part 2 of the ESSENCE trial is ongoing, with expected results in 2029. This second part aims to assess the impact of semaglutide 2.4 mg on reducing liver-related clinical events.
About MASH
Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease affecting over 250 million people globally. It is characterized by liver inflammation and damage due to fat accumulation. The condition often presents with few or no symptoms in its early stages, leading to delayed diagnosis and increased risk of progression to advanced liver disease, including liver cancer. The prevalence of MASH is particularly high among individuals who are overweight or obese, with more than one in three affected.
Trial Design
The ESSENCE trial is designed as a two-part study. In part 1, the primary objective was to demonstrate that semaglutide 2.4 mg improves liver histology at 72 weeks, based on biopsy samples from the first 800 randomized patients. Part 2 aims to show that semaglutide 2.4 mg reduces the risk of liver-related clinical events compared to placebo over 240 weeks.
About Semaglutide 2.4 mg
Semaglutide 2.4 mg, marketed as Wegovy®, is a GLP-1 receptor agonist approved as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults and adolescents with obesity. In the US, it is also indicated to reduce the risk of major adverse cardiovascular events (MACE) in adults with established cardiovascular disease who are either obese or overweight.
