Significant Improvement in Liver Fibrosis! Semaglutide Treatment Phase III Study Part 1 Successful, Application for New Indication Expected Next Year

On November 1, Novo Nordisk announced the primary positive results from the first part of the ongoing ESSENCE study of semaglutide, with plans to apply for regulatory approval in the US and EU in the first half of 2025.

ESSENCE is a 240-week Phase III double-blind trial designed to evaluate the efficacy of a weekly subcutaneous injection of 2.4 mg semaglutide in adult patients with metabolic dysfunction-associated fatty liver disease (MAFLD) and moderate to advanced liver fibrosis (stages 2 or 3). 

The ESSENCE trial consists of two parts, involving 1,200 patients randomly assigned in a 2:1 ratio to receive either 2.4 mg semaglutide or a placebo on top of standard treatment, for a duration of 240 weeks. The objective of the first part is to demonstrate, based on biopsy samples from the first 800 randomized patients, that 72 weeks of treatment with semaglutide 2.4 mg can improve liver histology. In the second part, the goal is to show that treatment with semaglutide 2.4 mg reduces the risk of liver-related clinical events in patients with MAFLD and moderate to advanced liver fibrosis at 240 weeks, compared to placebo.

The trial showed that semaglutide 2.4 mg significantly improves liver fibrosis compared to placebo, with no instances of worsening fatty liver disease; moreover, it also showed significant statistical significance in the relief of fatty liver disease without any worsening of liver fibrosis compared to placebo. At week 72, 37.0% of patients in the semaglutide 2.4 mg group had improved liver fibrosis with no worsening of fatty liver disease, while only 22.5% of placebo patients showed similar improvement. Furthermore, 62.9% of those on semaglutide 2.4 mg experienced relief from fatty liver disease without worsening liver fibrosis, compared to only 34.1% in the placebo group.

In this trial, the safety and tolerability of semaglutide 2.4 mg were consistent with previous trials.

“We are very pleased with the results of the ESSENCE clinical trial and the potential of semaglutide to help patients with MAFLD,” said Martin Holst Lange, Executive Vice President and Head of Development at Novo Nordisk. “One in three overweight or obese individuals has MAFLD. This poses a serious threat to their health and represents a significant unmet need.”

Detailed results from the ESSENCE study will be presented at a scientific conference in 2024. The second part of the ESSENCE study will continue, with results expected in 2029.