Survodutide Demonstrates Significant Improvement in Patients with Liver Fibrosis Associated with Metabolic Dysfunction-Associated Steatohepatitis

Image Credit: Adobe Stock Images/David A. Litman

Results from Boehringer Ingelheim’s Phase II MASH trial demonstrated that survodutide produced a major improvement in patients with fibrosis without worsening of metabolic dysfunction-associated steatohepatitis (MASH). According to the company, survodutide also demonstrated a clinically meaningful improvement in liver scarring across all fibrosis stages (F1 to F3) compared to placebo. Survodutide is the first glucagon/GLP-1 receptor dual agonist to demonstrate promising results in this area, according to the company.¹

“I am particularly excited about the findings of the Phase II trial in survodutide, which demonstrate the potential for glucagon agonism, in addition to GLP-1, to both improve MASH and shift the needle on fibrosis,” said Arun Sanyal, MD, professor of medicine, physiology and molecular pathology, Virginia Commonwealth University School of Medicine, principal investigator of the trial, in a press release. “These data position survodutide as a leading glucagon/GLP-1 receptor dual agonist that could be a game-changer for people living with MASH and clinically significant fibrosis.”

The randomized double-blind placebo-controlled dose-finding MASH trial enrolled 295 participants to evaluate weekly subcutaneous injections of survodutide in individuals living with MASH and fibrosis (F1, F2 and F3). The primary endpoint of this trial is the number of patients achieving histological improvement of MASH without worsening of fibrosis after 48 weeks of treatment. Secondary endpoints included a minimum of 30% relative reduction in liver fat content after 48 weeks of treatment compared to baseline, either complete or relative reduction in liver fat content after 48 weeks of treatment compared to baseline, improvement of fibrosis after 48 weeks of treatment, and a complete change from baseline in total score for MASH after 48 weeks of treatment.

The data showed that up to 64.5% of patients with moderate to advanced scarring experienced an improvement in fibrosis without MASH worsening compared to 25.9% in the placebo group after 48 weeks of treatment. Additionally, around 52.3% of adults treated with survodutide experienced a major improvement in liver scarring (fibrosis) across all three stages when treated with survodutide, compared with 25.8% in the placebo cohort after 48 weeks. Further, around 87% of patients in the survodutide arm achieved a minimum of 30% relative reduction in liver fat compared to 19.7% in the placebo group, with a relative reduction in liver fat content of up to 64.3% compared to 7.3% with placebo.

Safety results in the trial remained consistent with GLP-1 based molecules, as there were no new safety concerns reported. In 2021, survodutide received Fast Track Designation from the FDA and Priority Medicine Scheme from the European Medicines Agency this past November. Full results of the current data were presented at the European Association for the Study of the Liver Congress and published in The New England Journal of Medicine.

Currently, survodutide is also being tested across five different Phase III studies for patients who are overweight or struggle with obesity, a two-part Phase I trial in cirrhosis and liver dysfunction, and a Phase III trial determining whether survodutide can effectively reduce liver fat and weight loss among people living with overweight or obesity with a confirmed or presumed diagnosis of MASH.¹

“[These] breakthrough fibrosis results further reinforce survodutide’s potential as a best-in-class treatment for people living with MASH. We will advance quickly into Phase III trials,” said Carinne Brouillon, head of Human Pharma, Boehringer Ingelheim, in a press release. “New treatments are urgently needed for MASH, a disease connected with cardiovascular, renal and metabolic conditions like obesity, and we are excited to continue these important discussions with healthcare authorities.”

Reference

1. Boehringer Ingelheim’s survodutide shows breakthrough improvement in liver fibrosis with no worsening of MASH in 64.5% of patients with F2 and F3 fibrosi. Boehringer Ingelheim. June 7, 2024. Accessed June 7, 2024. https://www.boehringer-ingelheim.com/human-health/metabolic-diseases/breakthrough-phase-2-survodutide-data-liver-fibrosis-mash