Survodutide Improves Liver Fibrosis Without MASH Worsening in 64.5% of F2/F3 Patients

Boehringer Ingelheim has announced significant findings from a Phase II trial of survodutide, highlighting its efficacy in treating metabolic dysfunction-associated steatohepatitis (MASH) and related fibrosis. This news builds on the previously revealed primary endpoint, where 83.0% of adults experienced significant improvement in MASH compared to 18.2% with placebo.

The new data from the secondary endpoint reveal that up to 52.3% of patients with fibrosis stages F1, F2, and F3 showed improvement in fibrosis due to MASH after 48 weeks of treatment with survodutide, versus 25.8% with placebo. A further sub-analysis indicated that up to 64.5% of patients with moderate to advanced scarring (fibrosis stages F2 and F3) experienced fibrosis improvement without worsening MASH, compared to 25.9% who received placebo.

These findings were presented at the European Association for the Study of the Liver Congress (EASL) 2024 and published in The New England Journal of Medicine. The results underscore the potential of survodutide as a leading treatment for MASH, particularly given its novel mechanism as a glucagon/GLP-1 receptor dual agonist. The glucagon component is believed to increase energy expenditure and directly impact the liver, contributing to fibrosis improvement. Meanwhile, the GLP-1 component helps reduce appetite and increase feelings of fullness.

Dr. Arun Sanyal, a key figure in the trial, expressed excitement about these results, noting the promising role of glucagon agonism alongside GLP-1 in improving both MASH and fibrosis. The trial assessed the improvement as at least one stage decrease in fibrosis after 48 weeks. Fibrosis progression is crucial in MASH, which affects over 115 million people globally and can lead to severe liver diseases, including cirrhosis and liver cancer.

In addition to fibrosis improvement, survodutide showed positive results in all secondary endpoints. Up to 87.0% of patients achieved at least a 30% reduction in liver fat, compared to 19.7% with placebo. Moreover, the reduction in liver fat content reached up to 64.3% with survodutide, against 7.3% with placebo. The Non-alcoholic Fatty Liver Disease Activity Score (NAS), used to measure MASH improvement, significantly dropped by up to -3.3 with survodutide compared to -0.4 with placebo.

Carinne Brouillon, Head of Human Pharma at Boehringer Ingelheim, hailed these breakthrough results, emphasizing the urgent need for new MASH treatments, especially given its links to obesity and other metabolic conditions. She confirmed that Phase III trials would commence swiftly.

Survodutide, licensed to Boehringer Ingelheim by Zealand Pharma, has been granted Fast Track Designation by the U.S. FDA and access to the EMA PRIME Scheme for MASH with fibrosis. The drug is also being investigated in five Phase III studies for obesity and overweight individuals. These studies include sub-populations with comorbidities and aim to evaluate the impact of survodutide on liver fat reduction and weight loss.

This ongoing research is part of Boehringer Ingelheim’s commitment to developing innovative treatments that address significant unmet medical needs across cardiovascular, renal, and metabolic diseases. The findings from the Phase II trial position survodutide as a potentially transformative treatment for MASH and associated fibrosis, promising meaningful clinical benefits for patients worldwide.