China-based Ascletis Pharma Inc. (HKG: 1672) has announced that its first-in-class, once-daily oral fatty acid synthase (FASN) inhibitor, ASC40 (senifanstat), has successfully met primary and key secondary endpoints in a Phase II clinical trial for acne vulgaris.
ASC40’s Mechanism of Action and Trial Design
ASC40 is an oral, selective small-molecule inhibitor of FASN, with mechanisms targeting acne through direct inhibition of facial sebum production by inhibiting de novo lipogenesis (DNL) in human sebocytes, and by reducing inflammation through decreased cytokine secretion and Th17 differentiation. The randomized, double-blind, placebo-controlled, multicenter clinical trial in China evaluated the safety and efficacy of ASC40 for treating patients with moderate to severe acne. A total of 180 patients were enrolled and randomized into three active treatment arms or one placebo control arm at a 1:1:1:1 ratio to receive ASC40 (25 mg, 50 mg, or 75 mg) or matching placebo orally. Patients taking ASC40 at 25 mg, 50 mg, and 75 mg once daily for 12 weeks showed a significant response in skin lesions compared to the placebo group.
Safety and Efficacy of ASC40
ASC40 demonstrated a favorable safety profile with no grade 3 or 4 adverse events (AEs) or serious adverse events (SAEs) related to the drug. No deaths were reported during the trial. The oral, once-daily, 12-week treatment at all doses was well tolerated, indicating the potential for ASC40 to be a safe and effective treatment option for acne vulgaris.
Recommendations for Phase III and Other Developments
Based on the efficacy and safety assessment, a 50 mg, oral, once-daily dose of ASC40 is recommended for the Phase III clinical trial, which is expected to commence in the second half of 2023. The other two doses are under consideration for inclusion in the Phase III trial. ASC40 is also being developed for the treatment of nonalcoholic steatohepatitis (NASH) and recurrent glioblastoma in combination with bevacizumab, showcasing the drug’s potential in addressing multiple therapeutic areas.-Fineline Info & Tech
