Ascletis Pharma Inc. has announced the completion of enrollment for its Phase III clinical trial of ASC40 (denifanstat), a once-daily oral tablet intended for the treatment of moderate to severe acne. The trial, which enrolled a total of 480 patients, is a randomized, double-blind, placebo-controlled, multicenter study conducted in China.
The trial aims to evaluate the safety and efficacy of denifanstat, with patients randomized in a 1:1 ratio to receive either 50 mg of ASC40 or a matching placebo once daily for 12 weeks. The first patient was enrolled on January 24, 2024, and topline results are anticipated in the second quarter of 2025.
Primary Endpoints and Treatment Success
The primary efficacy endpoints of the trial include the proportion of patients achieving treatment success at week 12, the percentage change from baseline in total lesion count at week 12, and the percentage change from baseline in inflammatory lesion count at week 12. Treatment success is defined as at least a 2-point reduction in Investigator’s Global Assessment (IGA) score from baseline and an IGA score of clear (0) or almost clear (1).
Previous Phase II Results
Ascletis previously announced positive results from its Phase II clinical trial for denifanstat on May 2, 2023. The Phase II trial met its primary and key secondary endpoints, demonstrating superior efficacy compared to placebo, with 19.4% of patients achieving treatment success at week 12 versus 5.1% in the placebo group. The drug also exhibited a good safety profile.
Mechanism of Action
Denifanstat is a first-in-class, once-daily oral, selective small molecule inhibitor of fatty acid synthase (FASN). Its mechanisms of action for acne treatment involve direct inhibition of facial sebum production through the inhibition of de novo lipogenesis (DNL) in human sebocytes, as well as the reduction of inflammation by decreasing cytokine secretion and Th17 differentiation. Ascletis has licensed denifanstat from Sagimet Biosciences Inc. for exclusive rights in Greater China.
Executive Perspective
"As a first-in-class once-daily oral drug candidate with a novel mechanism for acne treatment, ASC40 has shown positive efficacy and a good safety profile in the Phase II study. We look forward to announcing topline results of the ASC40 (denifanstat) Phase III trial in the second quarter 2025," said Dr. Jinzi J. Wu, Founder, Chairman, and CEO of Ascletis.
