Sagimet Biosciences has announced that its lead drug candidate, denifanstat, has entered Phase III clinical trials for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). Denifanstat is an oral, selective fatty acid synthase (FASN) inhibitor. The advancement to Phase III follows successful interactions with the U.S. Food and Drug Administration (FDA) after the completion of Phase II studies. Earlier this month, the FDA granted Breakthrough Therapy Designation to denifanstat for the treatment of non-cirrhotic MASH, underscoring the urgent need for new therapies.
MASH, previously known as non-alcoholic steatohepatitis (NASH), is a chronic liver disease affecting over 115 million people worldwide. Currently, only one treatment is approved in the US and none in Europe, highlighting the significant unmet medical need.
Phase III Trial Design
The Phase III program is set to commence by the end of the year and will involve a minimum of 1,800 patients exposed to denifanstat. The program will consist of two double-blind, placebo-controlled, multicenter trials named FASCINATE-3 and FASCINIT. These trials will evaluate the efficacy and safety of denifanstat in patients diagnosed with MASH and metabolic dysfunction-associated steatotic liver disease (MASLD).
FASCINATE-3 will enroll patients with F2/F3 (non-cirrhotic) MASH, while FASCINIT will include patients with suspected or confirmed MASLD/MASH. The primary endpoints for FASCINATE-3 include liver biopsy results and clinical outcomes assessed over 4.5 years. FASCINIT will primarily focus on safety and tolerability, with secondary endpoints including non-invasive biomarkers.
Executive Commentary
Sagimet CEO Dave Happel commented, "Following the recent breakthrough therapy designation for denifanstat for the treatment of non-cirrhotic MASH, we are pleased with the outcome of our end-of-Phase II interactions with the FDA and are appreciative of the agency’s support and guidance on our Phase III program for denifanstat in MASH."
He further added, "The agency supports our strategy to conduct two Phase III trials to assess the safety and efficacy of denifanstat in F2/F3 MASH, a complex disease where treatments with novel/differentiated mechanisms of action that directly target the three main drivers of liver injury: fat accumulation, inflammation, and fibrosis are urgently needed."
