Survodutide, a Glucagon/GLP-1 RA, Reduces MASH in Phase 2 Trial

Arun Sanyal, MD
Credit: VCU

Use of survodutide was associated with a statistically significant improvement in metabolic dysfunction-associated steatohepatitis (MASH) without worsening fibrosis in a phase 2 trial, according to a release from Boehringer Ingelheim.

Announced on February 26, 2024, results of the trial indicate the glucagon/GLP-1 receptor dual agonist survodutide contributed to improvement of MASH without worsening fibrosis in 83% of patients with this difficult-to-treat metabolic condition. According to Boehringer Ingelheim, the company is examining the agent in 5 phase 3 trials among people with overweight and obesity.¹

“I am thrilled to see these statistically significant results from the Phase II trial of survodutide in MASH and fibrosis. These data position survodutide as a potential leading treatment for a population with great unmet medical needs, and will bring hope to people living with MASH and with fibrosis,” said principal investigator Arun Sanyal, MD, professor of Medicine, Physiology and Molecular Pathology at Virginia Commonwealth University School of Medicine.¹ “I am looking forward to sharing further detail on key secondary endpoints, including the percentage of adults who saw an improvement in fibrosis, at a congress in the first half of this year.”

Co-invented by Boehringer Ingelheim and Zealand Pharma, survodutide received a Fast Track Designation from the US Food and Drug Administration in 2021 for the treatment of MASH and fibrosis. At the American Diabetes Association 2023 Scientific Sessions, Carol Le Roux, MD, PhD, presented data from a phase 2 trial of the agent, then known as BI-456906, in patients with overweight and obesity without type 2 diabetes, which concluded use was associated with a mean body weight reduction of 14.9%, with more than 65% of those receiving the 4.8 mg dose experiencing body weight reductions of 15% or greater.^1,2

The phase 2 MASH trial was a randomized, double-blind, placebo-controlled, dose-finding trial of 295 participants and assessed the efficacy and safety of survodutide 2.4 mg, 4.8 mg, and 6.0 mg relative to placebo therapy. The trial’s primary outcome of interest was the percentage of participants achieving histological improvement of MASH without worsening fibroids at the conclusion of the 48-week treatment period.¹

For inclusion in the trial, patients needed to be living with MASH and have stage F1-F3 fibrosis. Of note, the trial included patients with and without type 2 diabetes. For the purpose of analysis, histological improvement of MASH was defined as a decrease of 2 or more points on the Non-alcoholic Fatty Liver Disease Activity Score, including a 1 point or greater decrease in NASH subscore for lobular inflammation or ballooning, and no increase in fibrosis stage.¹

According to Boehringer Ingelheim, use of survodutide was associated with statistically significant improvement in MASH, with 83.% of the survodutide arm achieving histological remission compared to 18.2% of the placebo arm (response difference, 64.8%; Confidence Interval 51.1-78.6; P < .0001). The release also pointed out improvement in the primary outcome was observed across all doses examined in the trial and the trial also met all key secondary endpoints, which included relative reduction in liver fat content of 30% or greater after 48 weeks, improvement of fibrosis, and absolute change from baseline in total score for NAS after 48 weeks.¹

Results of the trial’s safety analysis revealed there were no unexpected safety or tolerability issues, including with the 6.0 mg dose. In their release, Boehringer Ingelheim noted plans to present full data from the trial in the coming months.¹

“These MASH results show survodutide has potential to become a best-in-class treatment, and we believe its true differentiator is the action of the glucagon receptor agonism which works directly on the liver,” said Carinne Brouillon, head of Human Pharma at Boehringer Ingelheim.¹

References:

1. _{^{Boehringer Ingelheim. Survodutide Phase II trial shows 83% of adults treated achieved groundbreaking results in liver disease due to MASH, with significant improvements in fibrosis. Boehringer Ingelheim. February 26, 2024. Accessed February 26, 2024. https://www.boehringer-ingelheim.com/human-health/metabolic-diseases/survodutide-top-line-results-mash-fibrosis.}}
2. _{^{Campbell P. Survodutide, formerly Bi 456906, impresses in phase 2 dose-finding trial. HCP Live. June 23, 2023. Accessed February 26, 2024. https://www.hcplive.com/view/ada-2023-survodutide-impresses-in-phase-2-dose-finding-trial.}}