Sagimet's Denifanstat Advances to Phase III Trials for MASH Treatment

Key Insights

• Sagimet Biosciences' denifanstat, a FASN inhibitor, progresses to Phase III trials for metabolic dysfunction-associated steatohepatitis (MASH) after FDA support.
• The Phase III program includes two double-blind, placebo-controlled multicenter trials, FASCINATE-3 and FASCINIT, aiming to enroll a minimum of 1,800 patients.
• Denifanstat received breakthrough therapy designation from the FDA for treating non-cirrhotic MASH, a liver disease affecting over 115 million people globally.

Sagimet Biosciences has announced that its lead drug candidate, denifanstat, an oral, selective fatty acid synthase (FASN) inhibitor, is advancing into Phase III clinical trials for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). This progression follows successful interactions with the U.S. Food and Drug Administration (FDA) after Phase II trials.

The Phase III program is set to commence by the end of the year and will involve at least 1,800 patients receiving denifanstat. The program includes two double-blind, placebo-controlled, multicenter trials named FASCINATE-3 and FASCINIT.

Breakthrough Therapy Designation

Earlier this month, the FDA granted breakthrough therapy designation to denifanstat for the treatment of non-cirrhotic MASH. MASH, formerly known as non-alcoholic steatohepatitis (NASH), is a chronic liver disease affecting over 115 million people worldwide. Currently, there is only one approved treatment available in the US and none in Europe, highlighting a significant unmet medical need.

Trial Design and Endpoints

The FASCINATE-3 trial will focus on patients with F2/F3 (non-cirrhotic) MASH, while the FASCINIT trial will include patients with suspected or confirmed MASLD/MASH. The primary endpoints for FASCINATE-3 include liver biopsy results and 4.5-year clinical outcomes. The FASCINIT trial will primarily assess safety and tolerability, with secondary endpoints focusing on non-invasive biomarkers.

Sagimet's Perspective

Sagimet CEO Dave Happel stated, "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."

Happel 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."