Sagimet's Denifanstat Gains FDA Breakthrough Therapy Designation for MASH
Key Insights
Sagimet Biosciences' denifanstat receives Breakthrough Therapy designation from the FDA for treating non-cirrhotic MASH (search) with moderate to advanced liver fibrosis (search).
Phase 2b FASCINATE-2 study results of denifanstat, demonstrating significant improvements in MASH (search) resolution and fibrosis, were published in The Lancet.
Sagimet plans to initiate a Phase 3 program for denifanstat by the end of 2024, supported by successful end-of-Phase 2 interactions with the FDA.
Sagimet Biosciences Inc. (Nasdaq: SGMT) has announced significant progress in the development of denifanstat, a novel therapeutic for metabolic dysfunction-associated steatohepatitis (MASH (search)). The FDA granted Breakthrough Therapy designation to denifanstat for the treatment of non-cirrhotic MASH with moderate to advanced liver fibrosis (search) (F2-F3), potentially accelerating its approval pathway. This designation underscores the urgent need for new therapies to address this serious liver disease, which affects over 115 million people worldwide.
Phase 2b FASCINATE-2 Study Results
The results from the Phase 2b FASCINATE-2 clinical trial of denifanstat were published in The Lancet Gastroenterology & Hepatology. The study demonstrated that denifanstat achieved statistically significant and clinically meaningful improvements in disease activity, MASH (search) resolution, and fibrosis. These findings highlight denifanstat's potential to address the key drivers of MASH: fat accumulation, inflammation, and fibrosis.
Upcoming Phase 3 Program
Sagimet has successfully completed end-of-Phase 2 interactions with the FDA and plans to initiate a Phase 3 program for denifanstat by the end of 2024. The Phase 3 program will consist of two double-blind, placebo-controlled, multicenter registrational trials:
- FASCINATE-3: This trial will evaluate the efficacy and safety of denifanstat in patients with F2/F3 (non-cirrhotic) MASH. The primary endpoints will be liver biopsy assessments at 52 weeks, with Sagimet planning to seek accelerated approval in the US and Europe at this time. The trial will continue until the required number of clinical outcomes is reached, estimated at 3.5 years.
- FASCINIT: This trial will evaluate the efficacy and safety of denifanstat in patients with suspected or confirmed metabolic dysfunction-associated steatotic liver disease (MASLD)/MASH. The primary endpoints will be safety and tolerability at 52 weeks. Non-invasive biomarkers will be assessed as part of the secondary endpoints, without a liver biopsy endpoint.
The Phase 3 program is designed to include a minimum of 1,800 patients exposed to denifanstat.
Financial Position
As of September 30, 2024, Sagimet reported $170.0 million in cash, cash equivalents, and marketable securities. This includes $104.7 million in net proceeds from a January 2024 follow-on offering, which are expected to fund operations through 2025 based on the company's current operating plan.
Management Commentary
"As we approach the end of 2024, the Sagimet team remains focused on advancing denifanstat towards a pivotal Phase 3 program in MASH (search)," said David Happel, Chief Executive Officer of Sagimet. He emphasized denifanstat's differentiated mechanism of action and its potential to address the significant unmet need for new MASH therapies.