Boehringer gains FDA Breakthrough Therapy status and starts phase III MASH trials for survodutide

On October 8, 2024, Boehringer Ingelheim announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for survodutide (BI 456906). This dual glucagon/GLP-1 receptor agonist is being developed for treating adults with non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH) and moderate to advanced fibrosis (stages 2 or 3). The designation aims to speed up the development and review processes for treatments addressing serious or life-threatening conditions, where preliminary clinical evidence indicates substantial improvement compared to existing therapies.

Boehringer Ingelheim also announced the commencement of two Phase III clinical trials designed to evaluate survodutide's efficacy in treating adults with MASH and fibrosis. The LIVERAGE study will examine whether survodutide can improve MASH and/or fibrosis after 52 weeks and reduce the risk of end-stage liver disease outcomes over approximately seven years. The LIVERAGE-Cirrhosis study aims to determine whether survodutide can reduce the risk of end-stage liver disease outcomes over around four and a half years in adults with MASH and compensated cirrhosis (fibrosis stage 4).

Dr. Arun Sanyal, Professor of Medicine at Virginia Commonwealth University School of Medicine and Director of VCU’s Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, emphasized the significant burden of MASH and the need for novel therapeutic approaches. He expressed optimism about the potential of the LIVERAGE studies to address this medical need through survodutide’s dual glucagon and GLP-1 receptor agonist mechanism.

Shashank Deshpande, Head of Human Pharma at Boehringer Ingelheim, highlighted the importance of advancing the understanding and treatment of MASH, as the number of patients is expected to rise globally. He underscored that the Phase III trial program for survodutide is among the largest of its kind and aims to redefine the treatment landscape, specifically targeting patients with advanced fibrosis, including those with cirrhosis due to MASH.

Survodutide is licensed to Boehringer Ingelheim from Zealand Pharma, with Boehringer responsible for global development and commercialization. Zealand Pharma retains co-promotion rights in the Nordic countries.

The LIVERAGE and LIVERAGE-Cirrhosis trials are global Phase III clinical investigations to assess the efficacy and safety of survodutide in adults with MASH and fibrosis stages 2 or 3, and those with compensated MASH cirrhosis (stage 4), respectively. LIVERAGE plans to enroll about 1,800 adults, while LIVERAGE-Cirrhosis will enroll approximately 1,590 adults. Participants in both trials will be randomized to receive weekly injections of either survodutide, up to a maximum dose of 6 mg, or a placebo.

The LIVERAGE trial has two parts: the first part’s primary endpoints are the proportion of patients achieving MASH resolution without worsening fibrosis, and a 1-point improvement in fibrosis without worsening MASH after 52 weeks. The second part, extending over seven years, focuses on the time to the first occurrence of liver-related events or all-cause mortality. LIVERAGE-Cirrhosis will measure the time to the first occurrence of all-cause mortality or liver-related events over approximately four and a half years.

Survodutide’s dual action on glucagon and GLP-1 receptors targets metabolic functions, making it a promising candidate for addressing MASH and fibrosis. The robust Phase III clinical development program includes the LIVERAGE studies for MASH and fibrosis and the SYNCHRONIZE studies for individuals with overweight or obesity.

MASH, or metabolic dysfunction-associated steatohepatitis, is a chronic liver disease characterized by fat accumulation in the liver. It is a severe form of metabolic dysfunction-associated steatotic liver disease (MASLD). In the U.S., MASH cases are predicted to increase significantly from 16.5 million in 2015 to 27.0 million by 2030. The disease is closely linked to cardiovascular, renal, and metabolic conditions. It is estimated that 34% of individuals with obesity also suffer from MASH.

Boehringer Ingelheim is a leading biopharmaceutical company focusing on human and animal health. The company invests heavily in research and development to create innovative therapies for areas with high unmet medical needs. Established in 1885, Boehringer Ingelheim remains independent and committed to sustainability, employing over 53,500 people across 130 markets globally.