Denifanstat Sustains Acne Improvement Through 52 Weeks in Phase 3 Extension Study
Oral denifanstat, a once-daily fatty acid synthase (FASN) inhibitor under development for moderate to severe acne vulgaris, demonstrated sustained efficacy through 52 weeks in a Phase 3 open-label extension study.
The findings showed 57% Investigator’s Global Assessment (IGA) success, a 72% reduction in total acne lesions, and a 77% reduction in inflammatory lesions. Denifanstat was generally well tolerated.
The drug works by inhibiting FASN, reducing sebum lipid production and targeting inflammation involved in acne development. The findings were presented at the 2026 Fall Clinical Dermatology Conference in Las Vegas, highlighting its potential as an oral treatment option for moderate to severe acne.
The Phase 3 OLE clinical trial, ASC40-304, evaluated the long-term safety of denifanstat in patients with moderate to severe acne vulgaris who were previously enrolled in the 12-week randomized, double-blind, placebo-controlled Phase 3 ASC40-303 clinical trial. Both trials were conducted in China by Ascletis. 240 patients rolled over into the OLE trial, for a total trial duration of up to 52 weeks; 116 of those patients had received denifanstat in the original ASC40-303 trial, and 124 patients had received placebo. Primary endpoints of the OLE evaluated safety and secondary endpoints evaluated efficacy, including Investigator’s Global Assessment (IGA) success and reduction in total lesion count and inflammatory lesion count from baseline. Ascletis’ NDA submission for approval in China to the National Medical Products Association (NMPA) was accepted in December 2025.
2026 Fall Clinical Dermatology Conference Poster Presentation Details:
“The data being presented at the Fall Clinical Dermatology Conference highlight the potential and novel role of FASN inhibition to treat patients and families living with acne,” said David Happel, Chief Executive Officer of Sagimet. “Denifanstat has demonstrated significant and sustained improvements in moderate to severe acne through 52 weeks of treatment. With AURORA sites activated and patient screening beginning this month, we are excited to be advancing denifanstat into our U.S. Phase 3 program.”
About the Ascletis Phase 3 Clinical Trial and Open-Label Extension
ASC40-303 (NCT06192264) was a randomized, double-blind, placebo-controlled 12-week Phase 3 clinical trial of denifanstat in 480 patients with moderate to severe acne vulgaris, conducted in China by Ascletis. Patients were randomized 1:1 to denifanstat 50 mg or placebo once daily. Denifanstat met all primary and secondary endpoints and was generally well-tolerated.
ASC40-304 (NCT06248008) was a multi-center, open-label Phase 3 extension evaluating the long-term safety of denifanstat in patients with moderate to severe acne vulgaris who were previously enrolled in the double-blind, randomized, placebo-controlled 12-week Phase 3 ASC40-303 trial. This open-label Phase 3 trial enrolled 240 subjects who received oral denifanstat 50 mg once daily for up to 40 weeks. Subjects who were originally randomized to denifanstat in ASC40-303 trial had a total of up to 52 weeks of denifanstat exposure. Primary endpoints evaluated safety, and secondary endpoints evaluated efficacy, including the number of patients with IGA success and the reduction in total lesion count and inflammatory lesion count from baseline for up to 52 weeks of denifanstat treatment. Denifanstat was generally well-tolerated. Subjects treated with denifanstat showed improvements in all efficacy endpoints (secondary endpoints of the trial) beyond those observed at 12 weeks.
About the AURORA Phase 3 Clinical Trial
The AURORA (NCT07863193) multi-center, randomized, double-blind, placebo-controlled Phase 3 clinical trial of denifanstat in moderate to severe acne is intended to enroll approximately 800 U.S. patients aged 12 years and older, of which 450 are expected to be adolescents aged 12 to 17 years. Patients will be randomized 2:1 to receive denifanstat 50 mg or placebo once daily for 12 weeks. The trial will have three co-primary endpoints that will be assessed at week 12: the proportion of patients achieving treatment success in a global assessment score, defined as at least a 2-point reduction from baseline with a score of 0 (clear) or 1 (almost clear); absolute change in inflammatory skin lesion counts from baseline; and absolute change in non-inflammatory skin lesion counts from baseline. A subset of approximately 530 patients completing the double-blind period will be eligible to enter a 40-week open-label extension evaluating the long-term safety of denifanstat.
