FDA grants Breakthrough Therapy designation for denifanstat by Sagimet in MASH
Sagimet Biosciences has announced that the U.S. Food and Drug Administration (FDA) has awarded Breakthrough Therapy designation to denifanstat. This designation is for the treatment of noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver fibrosis, specifically stages F2 to F3.
The Breakthrough Therapy designation highlights the significant global prevalence of MASH and the ongoing demand for new treatment options. Denifanstat is unique as it inhibits fat synthesis and directly addresses the three main contributors to MASH: fat accumulation, inflammation, and fibrosis. This positions denifanstat as a promising treatment option for individuals living with MASH.
To qualify for Breakthrough Therapy designation, a treatment must target a serious or life-threatening condition, and initial clinical evidence must suggest that it could offer considerable improvements over existing therapies in important clinical outcomes.
Treatments designated as Breakthrough Therapy receive all the advantages of Fast Track designation, along with enhanced support from the FDA in terms of a streamlined drug development process and oversight from senior FDA officials.
The Breakthrough Therapy designation for denifanstat was backed by positive results from the Phase 2b FASCINATE-2 clinical trial, which involved patients with biopsy-confirmed MASH and stage 2 or stage 3 fibrosis.
In this trial, denifanstat demonstrated statistically significant improvements compared to a placebo across both primary endpoints: achieving MASH resolution without worsening fibrosis and a ≥2-point reduction in the Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS).
Additionally, patients treated with denifanstat showed a statistically significant improvement in fibrosis by ≥1 stage without worsening MASH. A higher percentage of these patients also achieved MRI-derived proton density fat fraction (MRI-PDFF) ≥30% responders compared to those on placebo.
In the intent-to-treat population, denifanstat produced significant results on both primary and secondary liver biopsy endpoints, aligning with the histological criteria recommended in the FDA's draft guidance for accelerated approval in MASH. Safety data suggested that denifanstat was largely well tolerated.
