Boehringer, Zealand Intensify MASH Race with Positive Phase II Results

In a recent development, Boehringer Ingelheim and Zealand Pharma announced promising Phase II results for their investigational drug survodutide, a GLP-1/glucagon receptor dual agonist. This drug showed significant efficacy in improving liver fibrosis in patients with metabolic dysfunction-associated steatohepatitis (MASH).

The clinical trial results, revealed after 48 weeks of treatment, indicated that survodutide markedly improved liver scarring. Specifically, 52.3% of patients with mild (F1) to advanced (F3) fibrosis experienced improvements, while only 25.8% of those receiving a placebo showed similar progress. This 26.5% treatment effect was statistically significant, underscoring the drug's potential benefits.

Furthermore, the data revealed that 64.5% of patients with moderate (F2) to advanced (F3) fibrosis saw liver scarring improvements without further worsening of MASH, compared to 25.9% in the placebo group. The treatment response of 38.6% was highly significant, reinforcing the drug's efficacy.

These findings were presented at the 2024 Congress of the European Association for the Study of the Liver and published simultaneously in The New England Journal of Medicine. Carinne Brouillon, head of human pharma at Boehringer Ingelheim, described these results as "breakthrough fibrosis results," indicating survodutide's potential to become a leading treatment for MASH. Brouillon confirmed that Boehringer Ingelheim plans to quickly advance the candidate into Phase III trials.

Survodutide, originally discovered and developed by Zealand Pharma, stands out due to its dual agonist mechanism, targeting both GLP-1 and glucagon receptors. These receptors play crucial roles in metabolic regulation, suggesting that survodutide might have advantages over existing single-hormone agonists.

Licensed to Boehringer Ingelheim by Zealand, survodutide's development and commercialization are managed globally by Boehringer. Zealand stands to benefit from milestone payments and royalties on global sales.

In addition to its application for MASH, Boehringer Ingelheim is also investigating survodutide for obesity. A June 2023 report indicated that survodutide could reduce body weight by approximately 20%. The company is currently conducting the Phase III SYCHRONIZE development program, which includes five late-stage trials. Three of these studies—SYNCHRONIZE-1, SYNCHRONIZE-2, and SYNCHRONIZE-CVOT—commenced in May 2023.

The recent data build on previous Phase II results for survodutide in MASH, released in February 2024. Those results showed that 83% of patients had significant biopsy-proven improvement in MASH, without worsening of fibrosis. In contrast, only 18.2% of patients in the placebo group achieved this endpoint.

These advancements position Boehringer Ingelheim and Zealand Pharma in direct competition with Eli Lilly. Earlier this week, Eli Lilly announced that its GLP-1/GIP dual receptor agonist tirzepatide also significantly improved fibrosis in MASH patients. At a 5-mg dose, tirzepatide reduced fibrosis by at least one stage in 54.9% of patients after 52 weeks of treatment, with additional benefits of around 17% body weight reduction.

These data highlight the competitive landscape in the development of treatments for MASH, with both survodutide and tirzepatide showing significant promise. As Phase III trials progress, the potential for these treatments to address liver fibrosis and metabolic dysfunction could mark a significant advancement in patient care.