Boehringer Gets FDA Breakthrough Status and Starts Phase III MASH Trials for Survodutide

Zealand Pharma has announced a significant milestone in the development of treatments for metabolic dysfunction-associated steatohepatitis (MASH). Boehringer Ingelheim, a partner of Zealand Pharma, has received the U.S. FDA Breakthrough Therapy designation for survodutide (BI 456906). This designation is aimed at accelerating the development and review process for treatments that show substantial improvements over current options for serious or life-threatening conditions.

Survodutide is a dual glucagon/GLP-1 receptor agonist, showing promising results in treating adults with non-cirrhotic MASH and moderate or advanced fibrosis (stages 2 or 3). The decision to grant this designation was based on groundbreaking results from Phase II studies, which indicated that survodutide could be a leading therapy for obesity-related MASH.

Boehringer Ingelheim has also initiated two significant Phase III clinical trials for survodutide. The first, named LIVERAGE, will investigate the efficacy of survodutide in improving MASH and fibrosis in approximately 1,800 adults over 52 weeks. The study aims to assess whether the treatment can reduce the risk of end-stage liver disease outcomes over roughly seven years. This trial focuses on individuals with moderate to advanced liver fibrosis (stages 2 or 3).

The second trial, LIVERAGE-Cirrhosis, will include around 1,590 adults with MASH and compensated cirrhosis (stage 4). This study will evaluate whether survodutide can lower the risk of end-stage liver disease outcomes over a period of approximately four and a half years.

Dr. David Kendall, Chief Medical Officer at Zealand Pharma, expressed enthusiasm about advancing survodutide into these Phase III trials. He highlighted the growing concern over obesity-related co-morbidities like MASH, which currently have limited treatment options. Dr. Kendall noted that the impressive Phase II data underscored survodutide’s potential as a leading incretin-based therapy for MASH and obesity.

LIVERAGE and LIVERAGE-Cirrhosis are global trials examining the safety and efficacy of survodutide. Participants in LIVERAGE will receive weekly injections of either survodutide or a placebo, with the primary endpoints being the proportion of patients achieving MASH resolution without worsening fibrosis and improvement in fibrosis without worsening MASH after 52 weeks. The trial will continue to monitor participants for approximately seven years to observe liver-related events or all-cause mortality.

The LIVERAGE-Cirrhosis trial has a similar structure but focuses on individuals with more severe liver conditions. The primary endpoint for this trial is the time to the first occurrence of all-cause mortality or liver-related events over about four and a half years.

Survodutide’s development has received recognition and support from various regulatory bodies. In addition to the U.S. FDA Breakthrough Therapy designation, it has been granted Fast Track designation by the U.S. FDA in May 2021. The European Medicines Agency included survodutide in its PRIME scheme in November 2023, and China’s National Medical Products Administration awarded it Breakthrough Therapy designation in June 2024. Boehringer Ingelheim holds the global development and commercialization rights for survodutide, with Zealand Pharma retaining co-promotion rights in the Nordic countries.

MASH is a severe form of metabolic dysfunction-associated steatotic liver disease (MASLD), characterized by a buildup of fat in the liver. It is closely linked with cardiovascular, renal, and metabolic diseases, with a significant portion of obese individuals also suffering from MASH. The disease is assessed using a fibrosis scale ranging from F0 (no fibrosis) to F4 (cirrhosis).

Zealand Pharma, founded in 1998 and headquartered in Copenhagen, Denmark, is dedicated to developing peptide-based medicines. The company has several drug candidates in clinical development and partnerships with various pharmaceutical companies.