Novo Nordisk's phase 3 ESSENCE trial has revealed positive results for semaglutide 2.4 mg in treating metabolic dysfunction-associated steatohepatitis (MASH). The double-blinded trial, involving 1,200 adults with MASH and moderate to advanced liver fibrosis, demonstrated significant improvements in liver histology compared to placebo. The company anticipates regulatory submissions in the US and EU in the first half of 2025.
The ESSENCE trial's primary endpoints were met at week 72, with 37.0% of patients treated with semaglutide 2.4 mg achieving 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 experienced resolution of steatohepatitis without worsening of liver fibrosis, versus 34.1% on placebo.
Impact on MASH Treatment
"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 highlighted the significant unmet need, noting that one in three people with overweight or obesity also live with MASH.
MASH affects over 250 million people globally, and the number of individuals in advanced stages of the disease is projected to double by 2030. The condition often presents with few or no specific symptoms in its early stages, leading to delayed diagnosis and increased risk of progression to advanced liver disease, including liver cancer.
Trial Design and Methodology
The ESSENCE trial is a phase 3 study evaluating once-weekly subcutaneous semaglutide 2.4 mg in adults with MASH and moderate to advanced liver fibrosis (stage 2 or 3). Participants were randomized 2:1 to receive semaglutide 2.4 mg or placebo, in addition to standard of care, over 240 weeks. Part 1 of the trial assessed liver histology at 72 weeks in the first 800 randomized patients, while Part 2 aims to demonstrate a reduction in liver-related clinical events at 240 weeks.
Semaglutide 2.4 mg (Wegovy)
Semaglutide 2.4 mg, marketed as Wegovy, is a GLP-1 receptor agonist. It is approved as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with obesity (BMI ≥ 30 kg/m2) or overweight (BMI ≥ 27 kg/m2) with at least one weight-related comorbidity, and in pediatric patients aged 12 years and older with obesity. In the US, Wegovy is also indicated to reduce the risk of major adverse cardiovascular events (MACE) in adults with established cardiovascular disease and either obesity or overweight.
