Novo’s obesity blockbuster semaglutide before label extension

Danish Novo Nordisk A/S has presented preliminary Phase III data from a two-part pivotal study in 1,200 adults with metabolic dysfunction-associated steatohepatitis (MASH) and moderate to advanced liver fibrosis (stage 2 or 3). In this part of the ESSENCE study, the effect of a once-weekly 2.4 mg dose of semaglutide in addition to standard treatment on liver histology after 72 weeks was investigated in 800 patients. Semaglutide met all primary endpoints and, if the rest of the study proceeds as expected, is about to be extended.

Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as ‘non-alcoholic steatohepatitis (NASH)’, is caused by metabolic inflammation of the liver. It is one of the main causes of liver fibrosis and cirrhosis.

At week 72, 37% of people treated with semaglutide achieved improvement in liver fibrosis without worsening steatohepatitis compared to 22.5% on placebo. 62.9% of people treated with semaglutide 2.4 mg achieved resolution of steatohepatitis without worsening of liver fibrosis, compared to 34.1% on placebo. There were no unknown side effects.

‘Among people who are overweight or obese, one in three are living with MASH,’ said Martin Holst Lange, Executive Vice President and Head of Development at Novo Nordisk, who sees a significant unmet medical need in this indication.

Novo Nordisk expects to submit marketing authorisation applications in the US and EU in the first half of 2025. Part 2 of the ESSENCE study will continue and is expected to be completed in 2029. Part 2 will demonstrate that treatment with semaglutide 2.4 mg in adults with MASH and moderate to advanced liver fibrosis reduces the risk of liver-related clinical events compared to placebo after 240 weeks.

In June, Eli Lilly has announced Phase II results of its SYNERGY-NASH trial in which 54.9% of patients on its dual GLP-1/GIP receptor agonist tirzepatide 5 mg, 51.3% of patients on tirzepatide 10 mg and 51% of patients on tirzepatide 15 mg saw their fibrosis decreaseby at least one stage without their metabolic dysfunction-associated steatohepatitis (MASH) worsening. That compared with just 29.7% of MASH patients in the placebo group who saw their fibrosis improve, according to a late-breaking abstract published ahead of the EASL International Liver Congress.

Both results are better than those obtained with the approved treatmen resmetirom (Rezdiffra) from Madrigal Pharmaceuticals Inc. Eli Lilly and Novo Nordisk have become No 1 and No 2 of the pharma companies concerning annual sales particularly due to the success of their obesity and diabetes drugs.