Sagimet Receives FDA Breakthrough Therapy Designation for Denifanstat in MASH

Sagimet Biosciences Inc. recently announced the US FDA granted Breakthrough Therapy designation to denifanstat for treatment of noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis).

“The FDA’s Breakthrough Therapy designation for denifanstat underscores the global incidence of MASH and the continuing need for new therapies,” said David Happel, Chief Executive Officer of Sagimet. “As the only fat synthesis inhibitor that directly targets the three main drivers of MASH— fat accumulation, inflammation, and fibrosis— we believe denifanstat is well-positioned to offer a leading treatment option for patients living with MASH.”

Treatments that receive Breakthrough Therapy designation must target a serious or life-threatening disease and preliminary clinical evidence must indicate that the drug may demonstrate a substantial improvement over existing therapies on one or more clinically significant endpoints. Drugs that receive Breakthrough Therapy designation are eligible for all the benefits of Fast Track designation, as well as intensive guidance by FDA on an efficient drug development program and organizational commitment involving FDA senior managers.

Breakthrough Therapy designation of denifanstat was supported by positive data from the Phase 2b FASCINATE-2 clinical trial in biopsy-confirmed MASH patients with stage 2 or stage 3 fibrosis. In the trial, denifanstat showed statistically significant improvements relative to placebo on both primary endpoints of MASH resolution without worsening of fibrosis with ≥2-point reduction in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS), and ≥2-point reduction in NAS without worsening of fibrosis. Denifanstat-treated patients also showed statistically significant fibrosis improvement by ≥ 1 stage with no worsening of MASH, and a statistically significantly greater proportion of MRI-derived proton density fat fraction (MRI-PDFF) ≥30% responders relative to placebo. In the intent to treat (ITT) population, denifanstat achieved statistically significant results on primary and secondary liver biopsy endpoints, including both histology endpoints recommended in the FDA draft guidance for accelerated approval in MASH. Safety data showed that denifanstat was generally well tolerated. The Company plans to initiate the Phase 3 clinical program for denifanstat in MASH by the end of 2024.

MASH is a progressive and severe liver disease which is estimated to impact more than 115 million people worldwide, for which there is only one recently approved treatment in the United States and no currently approved treatments in Europe. In 2023, global liver disease medical societies and patient groups formalized the decision to rename non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated steatotic liver disease (MASLD) and nonalcoholic steatohepatitis (NASH) to MASH. Additionally, an overarching term, steatotic liver disease (SLD), was established to capture multiple types of liver diseases associated with fat buildup in the liver. The goal of the name change was to establish an affirmative, non-stigmatizing name and diagnosis.

Sagimet is a clinical-stage biopharmaceutical company developing novel fatty acid synthase (FASN) inhibitors that are designed to target dysfunctional metabolic pathways in diseases resulting from the overproduction of the fatty acid, palmitate. Sagimet’s lead drug candidate, denifanstat, is an oral, once-daily pill and selective FASN inhibitor in development for the treatment of MASH. FASCINATE-2, a Phase 2b clinical trial of denifanstat in MASH with liver biopsy-based primary endpoints, was successfully completed with positive results. For additional information about Sagimet, please visit www.sagimet.com.