Positive Phase 2b Results for Denifanstat in F2/F3 NASH Trial

In a recent clinical trial, denifanstat, a drug developed by Sagimet Biosciences Inc., demonstrated significant effectiveness in treating non-alcoholic steatohepatitis (NASH) in patients with stage 2 or 3 fibrosis. The 52-week study involved 168 participants and compared the outcomes of those who received denifanstat to those who received a placebo.

The primary goals of the trial were to assess NASH resolution without an increase in fibrosis and a reduction in NAS (NAFLD Activity Score) by at least 2 points. In the group treated with denifanstat, 36% of patients achieved NASH resolution without fibrosis worsening, compared to only 13% in the placebo group, with a p-value of 0.002. Additionally, a reduction in NAS by at least 2 points without fibrosis worsening was observed in 52% of denifanstat-treated patients versus 20% in the placebo group, with a p-value of 0.0001.

Secondary endpoints also showed promising results. Fibrosis improvement by at least one stage without NASH worsening was noted in 41% of patients treated with denifanstat, compared to 18% in the placebo group, with a p-value of 0.005. MRI-PDFF, a measure of liver fat, showed a decline of at least 30% from baseline in 65% of denifanstat-treated patients, significantly higher than the 21% observed in the placebo group, with a p-value less than 0.0001.

The drug was found to be generally well-tolerated, with no serious adverse events related to treatment. Most side effects were mild to moderate. Sagimet Biosciences is planning an End-of-Phase 2 meeting with the FDA and intends to start a Phase 3 program for denifanstat in the second half of 2024.

Denifanstat works by targeting the fatty acid synthase (FASN) enzyme, which plays a crucial role in the development of NASH and its progression to cirrhosis. The drug is designed to reduce fat accumulation, inflammation, and fibrosis, which are the main drivers of NASH. The positive results from the trial indicate that blocking fatty acid synthesis in the liver is a critical approach for treating NASH and improving fibrosis.

Sagimet Biosciences is a clinical-stage biopharmaceutical company focused on developing FASN inhibitors to target dysfunctional metabolic pathways. Denifanstat is their lead drug candidate for the treatment of NASH, a condition for which there are currently no approved treatments in the United States or Europe. The successful completion of the Phase 2b FASCINATE-2 clinical trial with positive results is a significant milestone for the company and the treatment of NASH.