Ascletis Pharma Inc. has announced the completion of enrollment for its Phase III clinical trial of ASC40 (denifanstat), a once-daily oral tablet being investigated 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 study aims to evaluate the safety and efficacy of denifanstat in patients with moderate to severe acne vulgaris. Participants were randomized in a 1:1 ratio to receive either 50 mg of oral denifanstat once daily or a matching placebo for a duration of 12 weeks. The first patient was enrolled on January 24, 2024, and topline results are expected in the second quarter of 2025.
The primary efficacy endpoints of the trial include the proportion of patients achieving treatment success at week 12, defined as at least a 2-point reduction in Investigator’s Global Assessment (IGA) score from baseline and a score of clear (0) or almost clear (1). Additional primary endpoints are the percentage change from baseline in total lesion count and inflammatory lesion count at week 12.
Novel 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.
Prior Clinical Evidence
Previously, Ascletis announced positive results from a Phase II clinical trial of denifanstat for acne vulgaris. The Phase II trial met its primary and key secondary endpoints, demonstrating superior efficacy compared to placebo. Specifically, 19.4% of patients achieved treatment success at week 12 in the denifanstat arm, compared to 5.1% in the placebo arm. The drug also exhibited a good safety profile.
Management 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," stated Dr. Jinzi J. Wu, Founder, Chairman, and CEO of Ascletis.
