Sagimet Biosciences Reports Positive Phase 2b Results for Denifanstat in F2/F3 NASH

In a recent clinical trial, denifanstat demonstrated significant efficacy in patients with non-alcoholic steatohepatitis (NASH) who possess moderate-to-severe fibrosis. Conducted over a 52-week period, the Phase 2b FASCINATE-2 study involved 168 patients diagnosed with stage 2 or 3 fibrosis through biopsy. The treatment group received a 50 mg daily dose of denifanstat, an oral selective FASN inhibitor, while a control group was administered a placebo.

The study’s primary endpoints showcased promising results. Specifically, 36% of denifanstat-treated patients experienced NASH resolution without any fibrosis progression and achieved a ≥2-point reduction in the NAFLD Activity Score (NAS), compared to just 13% in the placebo group. Furthermore, 52% of those treated with denifanstat saw a ≥2-point decrease in NAS without worsening fibrosis, against 20% in the placebo cohort. These differences were statistically significant, underscoring the potential of denifanstat in treating NASH.

Secondary endpoints also revealed substantial improvements. Among the patients receiving denifanstat, 41% demonstrated fibrosis improvement by at least one stage without worsening NASH, compared to 18% in the placebo group. Additionally, 38% of the denifanstat group achieved NASH resolution without any fibrosis deterioration, versus 16% in the control group. These outcomes bolstered the evidence supporting the efficacy of denifanstat.

Beyond efficacy, the trial assessed several other measures such as ALT percentage change from baseline and MRI-PDFF responder rates. Denifanstat-treated patients exhibited a mean ALT reduction of 30.5%, against 17.2% in the placebo group. Also, 65% of those on denifanstat met the criteria for MRI-PDFF responders, defined as a ≥30% relative reduction of liver fat, while only 21% of the placebo group reached this mark.

Safety and tolerability were carefully monitored throughout the trial. Denifanstat was generally well-tolerated, with no serious adverse events (SAEs) linked to treatment. Most adverse events (AEs) were classified as mild to moderate. Common AEs included disorders related to the eyes, gastrointestinal system, and skin. Treatment-related discontinuation rates were higher in the denifanstat group (19.6%) compared to the placebo group (5.4%).

Gannex Pharma Co., a subsidiary of Ascletis, holds exclusive rights to develop, manufacture, and market denifanstat in Greater China, under a license agreement with Sagimet Biosciences. Gannex, founded in 2019, focuses on discovering and developing new treatments for NASH and has brought forward three clinical-stage drug candidates targeting FASN, THRβ, and FXR.

Sagimet Biosciences’ announcement of these results highlights the significant potential of denifanstat in addressing the severe and currently unmet needs in NASH treatment. As the company continues to move forward, the positive outcomes of this trial mark a crucial step in the drug’s development and future clinical applications.