FDA Grants Survodutide Breakthrough Therapy Designation for Treatment of Adults With MASH

Survodutide (BI 456906; Boehringer Ingelheim) was granted a breakthrough therapy designation by the FDA for treatment of non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH) and moderate or advanced fibrosis in adults. The decision is based on positive results from a phase 2 study (NCT04771273) and will pave the way to continued investigations of survodutide.¹

The researchers reported adverse effects such as nausea, diarrhea, and vomiting were more frequent in patients receiving survodutide. Image Credit: © Yura Yarema - stock.adobe.com

MASH is a chronic, progressive liver disease characterized by the excessive buildup of fat in the liver, resulting in aching of the upper abdomen, weakness and fatigue, loss of appetite, and unexplained weight loss, as well as jaundice in more advanced stages. It is a more severe form of metabolic dysfunction-associated steatotic liver disease and closely linked to interconnected cardiovascular, renal, and metabolic conditions. In the United States, there is an anticipated rise in cases by 63% between 2015 and 2030.^2,3

Lifestyle modifications in combination with medications is the standard treatment for MASH. The advent of glucagon-like peptide-1 (GLP-1) receptor agonists has greatly expanded therapeutic options for patients across various disease states, including MASH. In the phase 2 study, researchers investigated the use of survodutide, a glucagon/GLP-1 receptor dual agonist that activates the glucagon and GLP-1 receptors to better control metabolic function.^2,3

In the 48-week, 293 adults with biopsy-confirmed MASH and fibrosis stage F1 through F3 were randomly assigned in a 1:1:1:1 ratio to receive once-weekly subcutaneous injections of survodutide at a dose of 2.4, 4.8, or 6.0 mg, or placebo. The first phase of the trial consisted of a 24-week, rapid-dose-escalation phase, followed by a 24-week maintenance phase. The safety and efficacy of survodutide was determined based on reduction in MASH with no worsening of fibrosis, as well as a decrease in liver fat content by at least 30% and biopsy-assessed reduction in fibrosis by at least 1 stage.⁴

According to the data, survodutide demonstrated a 47% improvement in MASH with no worsening of fibrosis at a dose of 2.4 mg, 62% at the 4.8 mg dosage, and 43% at the 6.0-mg dosage as compared with 14% of those in the placebo group. There was a 30% decrease in liver fat content in 63% of the participants in the survodutide 2.4 mg group, 67% of those in the 4.8 mg group, 57% of those in the 6.0 mg group, and 14% of those in the placebo group.⁴

The researchers reported adverse effects such as nausea, diarrhea, and vomiting were more frequent in patients receiving survodutide compared with placebo.⁴

“Given the significant burden of MASH and the limited therapeutic options, novel approaches are urgently needed,” Arun Sanyal, MD, professor of medicine at Virginia Commonwealth University (VCU) School of Medicine and director of VCU’s Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, said in a press release. “The phase 3 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.”³

REFERENCES

1. A study to test safety and efficacy of bi456906 in adults with non-alcoholic steatohepatitis (nash) and fibrosis (f1-f3). ClinicalTrials.gov Identifier: NCT04771273. Updated April 30, 2024. Accessed October 8, 2024. https://clinicaltrials.gov/study/NCT04771273

2. Metabolic dysfunction-associated steatohepatitis. Cleveland Clinic. May 3, 2022. Accessed October 8, 2024. https://my.clevelandclinic.org/health/diseases/22988-nonalcoholic-steatohepatitis

3. 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

4. Sanyal A, Bedossa P, Fraessdorf M, et al. A phase 2 randomized trial of survodutide in mash and fibrosis. N Engl J Med. June 7, 2024. doi: 10.1056/NEJMoa2401755