Novo Nordisk: Semaglutide 2.4 mg excels in liver fibrosis and MASH resolution in ESSENCE trial

Bagsværd, Denmark, 1 November 2024 – Novo Nordisk has announced the headline results from part 1 of the ongoing ESSENCE trial, a phase 3, 240-week, double-blinded trial involving 1,200 adults with metabolic dysfunction-associated steatohepatitis (MASH) and moderate to advanced liver fibrosis (stage 2 or 3). This section of the trial focused on the effects of once-weekly semaglutide 2.4 mg on liver histology compared to a placebo, alongside standard care in the first 800 randomized participants over 72 weeks.

The trial achieved its primary goals by showing significant improvement in liver fibrosis without worsening steatohepatitis and resolving steatohepatitis without worsening liver fibrosis with semaglutide 2.4 mg compared to a placebo. By week 72, 37% of the participants treated with semaglutide 2.4 mg saw an improvement in liver fibrosis with no worsening of steatohepatitis, compared to 22.5% who received a placebo. Additionally, 62.9% of those on semaglutide 2.4 mg achieved resolution of steatohepatitis with no worsening of liver fibrosis, as opposed to 34.1% on the placebo.

Throughout the trial, semaglutide 2.4 mg demonstrated a safe and well-tolerated profile consistent with previous trials of the same dosage. Martin Holst Lange, executive vice president and head of Development at Novo Nordisk, expressed satisfaction with the results, highlighting the potential of semaglutide to aid people living with MASH. Lange emphasized the significant health impact of MASH on individuals with overweight or obesity, noting that approximately one in three individuals within these groups are affected by the disease.

Novo Nordisk plans to seek regulatory approvals in the US and EU during the first half of 2025. Detailed results from the ESSENCE trial will be presented at a scientific conference in 2024. The second part of the ESSENCE trial will continue, with results expected in 2029.

Metabolic dysfunction-associated steatohepatitis (MASH) is a serious liver condition that can progress and become life-threatening if not managed appropriately. Over 250 million people worldwide suffer from MASH, and the number of individuals in advanced stages of the disease is projected to double by 2030. MASH is prevalent among those who are overweight or obese, with over one-third of such individuals affected. Early stages of MASH often present few or no symptoms, leading to delayed diagnosis. The risk of advancing to severe liver disease, including liver cancer, is higher in people with MASH compared to the general population.

The ESSENCE trial is a phase 3 study assessing the impact of once-weekly subcutaneous semaglutide 2.4 mg in adults with MASH and moderate to advanced liver fibrosis (stage 2 or 3). This two-part trial included 1,200 participants randomized in a 2:1 ratio to receive either semaglutide 2.4 mg or a placebo alongside standard care for 240 weeks. The first part aimed to demonstrate the effects of semaglutide 2.4 mg on liver histology at 72 weeks, based on biopsy samples from the first 800 randomized patients. The second part aims to show that semaglutide 2.4 mg reduces the risk of liver-related clinical events compared to a placebo in adults with MASH and moderate to advanced liver fibrosis over 240 weeks.

Semaglutide 2.4 mg, marketed under the brand name Wegovy®, is a once-weekly GLP-1 receptor agonist. Wegovy® is prescribed alongside a reduced-calorie diet and increased physical activity for chronic weight management in adults with a BMI of 30 kg/m² or greater (obesity), adults with a BMI of 27 kg/m² or greater (overweight) with at least one weight-related comorbid condition, and pediatric patients aged 12 years and older with a BMI at the 95th percentile or greater for age and gender (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, and to aid in long-term weight reduction in adults and pediatric patients aged 12 years and older with obesity, as well as in adults with overweight conditions with at least one weight-related comorbidity.