Sagimet Biosciences Completes FDA Phase 2 Meeting for Denifanstat; Phase 3 to Start by End of 2024

Sagimet Biosciences Inc., a biopharmaceutical company that focuses on creating new treatments targeting metabolic and fibrotic pathways, has recently announced a significant milestone. On October 29, 2024, they confirmed the successful completion of their end-of-Phase 2 discussions with the U.S. Food and Drug Administration (FDA), allowing them to advance their lead drug candidate, denifanstat, into Phase 3 clinical trials for metabolic-dysfunction associated steatohepatitis (MASH).

The upcoming Phase 3 program will be comprised of two multicenter, double-blind, placebo-controlled trials named FASCINATE-3 and FASCINIT. These trials will be crucial in evaluating both the safety and efficacy of denifanstat. The FASCINATE-3 trial will focus on patients with F2/F3 (non-cirrhotic) MASH, while the FASCINIT trial will target individuals with a confirmed or suspected diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD)/MASH. The initiation of these trials is expected by the end of 2024.

Dave Happel, the CEO of Sagimet, expressed satisfaction with the FDA's support and guidance. He highlighted the importance of conducting two Phase 3 trials to address the safety and effectiveness of denifanstat in treating F2/F3 MASH. Happel emphasized the need for treatments that directly tackle fat accumulation, inflammation, and fibrosis, which are the primary drivers of liver injury in MASH.

According to ongoing consultations with the FDA, the planned Phase 3 studies will include a minimum of 1,800 patients receiving denifanstat. Both trials will be placebo-controlled and double-blind, ensuring objective results. The FASCINATE-3 trial's primary endpoints will involve liver biopsy and a 4.5-year period focusing on clinical outcomes. In contrast, the FASCINIT trial will focus on the safety and tolerability of denifanstat, utilizing non-invasive biomarkers as part of the secondary endpoints and eliminating the need for end-of-treatment liver biopsies.

MASH is a progressively severe liver condition, impacting an estimated 115 million individuals globally. There is only one newly approved treatment available in the United States, with no current treatments approved in Europe. In 2023, medical societies and patient groups globally adopted the terms metabolic dysfunction-associated steatotic liver disease (MASLD) to replace non-alcoholic fatty liver disease (NAFLD) and metabolic-dysfunction associated steatohepatitis (MASH) to replace nonalcoholic steatohepatitis (NASH). An overarching term, steatotic liver disease (SLD), was introduced to encompass various liver diseases linked to fat accumulation. This terminology change aims to provide a positive, non-stigmatizing diagnosis.

Sagimet Biosciences is a clinical-stage company that specializes in developing novel fatty acid synthase (FASN) inhibitors to target diseases caused by excessive fatty acid production, particularly palmitate. Denifanstat, an oral, once-daily pill, is Sagimet’s leading drug candidate for treating MASH. The Phase 2b clinical trial, FASCINATE-2, which used liver biopsy-based primary endpoints, was successfully completed, yielding positive results.

With the support of the FDA, Sagimet is now poised to commence two critical Phase 3 trials aimed at addressing the urgent need for effective treatments for MASH and MASLD. As the company moves forward, these trials are expected to provide essential data on the safety and efficacy of denifanstat, potentially offering a new therapeutic option for patients suffering from these severe liver conditions.