Sagimet Biosciences has announced the progression of its lead candidate, denifanstat, an oral, selective fatty acid synthase (FASN) inhibitor, into Phase III trials for treating metabolic dysfunction-associated steatohepatitis (MASH).
The US Food and Drug Administration (FDA) has supported the advancement following successful end-of-Phase II interactions.
Earlier this month, the FDA granted breakthrough therapy designation to the therapy for treating non-cirrhotic MASH.
Formerly known as non-alcoholic steatohepatitis (NASH), MASH is a chronic liver disease affecting more than 115 million individuals globally. There is currently only one approved treatment in the US and none in Europe.
The Phase III programme is expected to begin by the end of this year and is aiming to include a minimum of 1,800 patients exposed to denifanstat.
It will include two double-blind, placebo-controlled multicentre trials, FASCINATE-3 and FASCINIT.
These trials will assess the efficacy and safety of denifanstat in patients with MASH and metabolic dysfunction-associated steatotic liver disease (MASLD).
Sagimet CEO Dave Happel said: “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 programme for denifanstat in MASH.
“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.”
FASCINATE-3 will focus on patients with F2/F3 (non-cirrhotic) MASH while FASCINIT will involve those with a suspected or confirmed diagnosis of MASLD/MASH.
The primary endpoints for FASCINATE-3 are liver biopsy and 4.5-year clinical outcomes, whereas FASCINIT will focus on safety and tolerability, with secondary endpoints including non-invasive biomarkers.
