FDA Grants Breakthrough Therapy Designation to Boehringer Ingelheim’s Survodutide for Non-Cirrhotic Metabolic Dysfunction-Associated Steatohepatitis

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The FDA has granted Breakthrough Therapy designation to Boehringer Ingelheim’s survodutide (BI 456906), a dual glucagon/GLP-1 receptor agonist for adults with non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH) and moderate to advanced fibrosis. According to the company, the Breakthrough Designation was based on preliminary clinical data, which demonstrated potential improvement over existing therapies for MASH and moderate to advanced fibrosis. Moving forward, Boehringer will evaluate survodutide in two Phase III trials, LIVERAGE and LIVERAGE-Cirrhosis.¹

“Given the significant burden of MASH and the limited therapeutic options, novel approaches are urgently needed,” said Arun Sanyal, MD, professor of medicine, Virginia Commonwealth University School of Medicine, director, VCU’s Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, in a press release. “The Phase III LIVERAGE studies represent an exciting opportunity to investigate whether survodutide, with its dual glucagon and GLP-1 receptor agonist mechanism of action, can help address this significant medical need.”

LIVERAGE and LIVERAGE-Cirrhosis are global clinical trials investigating the efficacy and safety of survodutide in adults with MASH and fibrosis stages 2 or 3, and in those with compensated MASH cirrhosis, respectively. The LIVERAGE trial will enroll approximately 1,800 adults and is divided into two parts.

The primary endpoints of the first part of LIVERAGE are proportion of patients achieving MASH resolution without worsening of fibrosis, and at least a one-point improvement in fibrosis without worsening of MASH, after 52 weeks of treatment. For part two, the primary endpoint is time to first occurrence of liver-related events or all-cause mortality after seven years. LIVERAGE-Cirrhosis will enroll approximately 1,590 adults with the primary endpoint of time to first occurrence of all-cause mortality or liver-related events. Both studies are expected to randomly assign patients to receive weekly injections of either survodutide, reaching a maximum dose of 6 mg, or placebo.¹

Boehringer Ingelheim states that an estimated 250 million people are currently living with MASH globally. It is considered a more serious form of metabolic dysfunction associated steatotic liver disease, which is the most common liver disease in Western industrialized nations, affecting one out of four adults.² In the United States, cases are expected to rise by 63% between 2015 and 2030, from 16.5 million to 27.0 million cases. It is also estimated that 34% of people living with obesity also have MASH.¹

From 2016-2020, approximately 1.8 million people in the United States were diagnosed with MASH. Further, it is the biggest cause for liver transplants in women and patients over 65 years of age in the United States.³

"With the number of MASH patients expected to rise worldwide in the coming years, advancing our understanding of this condition is more crucial than ever," said Shashank Deshpande, head, human pharma, Boehringer Ingelheim, in the press release. "Our Phase III trial program with survodutide is one of the largest of its kind in terms of countries and sites involved. Notably, the program’s innovative design, which specifically targets advanced fibrosis including patients living with cirrhosis due to MASH – the most in-need population, is set to redefine the treatment landscape. The Breakthrough Therapy designation underscores that this potential best-in-class therapy has an opportunity to fundamentally change how MASH is treated."

Survodutide is licensed to both Boehringer Ingelheim and Zealand Pharma. Boehringer Ingelheim will be solely responsible for global development and commercialization, with Zealand Pharma having a co-promotion right in the Nordic countries.¹

References

1. Boehringer receives U.S. FDA Breakthrough Therapy designation and initiates two phase III trials in MASH for survodutide. Boehringer Ingelheim. October 8, 2024. Accessed October 8, 2024. https://www.boehringer-ingelheim.com/human-health/metabolic-diseases/survodutide-us-fda-breakthrough-therapy-phase-3-trials-mash

2. MASH. Boehringer Ingelheim. Accessed October 8, 2024. https://www.boehringer-ingelheim.com/human-health/metabolic-diseases/mash

3. About MASH. MASH Awareness. Accessed October 8, 2024. https://www.mashawareness.com/?&utm_source=google&utm_medium=cpc&utm_term=mash&utm_campaign=MASH_Acronym&mkwid=s-dc_pcrid_701588700365_pkw_mash_pmt_p_slid__product_&pgrid=165974104689&ptaid=kwd-298859835515&gad_source=1&gclid=Cj0KCQjwsJO4BhDoARIsADDv4vA2YkR-hWWyoN3UEgykP2UMh6UFF49Ennr-Cna0m-HkZ5SlGY0EHZEaArLrEALw_wcB&gclsrc=aw.ds