Sagimet Biosciences Inc. (SGMT) announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to denifanstat for the treatment of noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis). This designation highlights the potential of denifanstat to address a critical unmet need in patients with MASH, a severe form of non-alcoholic fatty liver disease (NAFLD). The stock traded up over 11% in the pre-market in reaction to the news.
Clinical Significance of Breakthrough Therapy Designation
The FDA's Breakthrough Therapy designation is intended to expedite the development and review of drugs for serious or life-threatening conditions. To qualify, preliminary clinical evidence must indicate that the drug may demonstrate substantial improvement over available therapies on at least one clinically significant endpoint. This designation provides Sagimet with increased access to the FDA, including more frequent meetings and guidance, potentially accelerating the path to market for denifanstat.
Denifanstat: A Novel FASN Inhibitor
Denifanstat is a first-in-class, oral fatty acid synthase (FASN) inhibitor. FASN is a key enzyme in the de novo lipogenesis (DNL) pathway, which is responsible for the synthesis of fatty acids from non-lipid precursors. In MASH, DNL is often upregulated, leading to excessive fat accumulation in the liver, inflammation, and fibrosis. By inhibiting FASN, denifanstat aims to reduce hepatic fat accumulation, improve liver function, and resolve MASH.
Ongoing Phase 3 Program
Sagimet is currently preparing to initiate a Phase 3 clinical program for denifanstat by the end of 2024. This pivotal trial will evaluate the efficacy and safety of denifanstat in a larger population of patients with MASH and moderate to advanced liver fibrosis. The primary endpoints of the Phase 3 trial are expected to include resolution of MASH without worsening of fibrosis and improvement in fibrosis stage by at least one stage without worsening of MASH. Successful completion of this trial could pave the way for regulatory approval and commercialization of denifanstat.
Current Treatment Landscape for MASH
MASH is a progressive liver disease that affects millions of people worldwide. Currently, there are limited approved therapies for MASH, and treatment primarily focuses on lifestyle modifications, such as diet and exercise. The development of effective pharmacologic therapies for MASH is a major area of unmet medical need. Denifanstat represents a promising new approach to treating MASH by targeting the underlying metabolic dysfunction that drives disease progression.
