The board of directors of the Ascletis Pharma Inc. announced the completion of 180 patient enrollment for the Phase II clinical trial of ASC40 (denifanstat) for treatment of moderate to severe acne. The study is currently still blind. To date, approximately 50% enrolled patients have completed 12-week treatment and all enrolled patients are expected to complete 12-week treatment by the end of February 2023.

Clinical efficacy observed in patients who have completed 12-week treatment of ASC40 or placebo was comparable to that from two recently approved acne drugs by U.S. Food and Drug Administration ­ WINLEVI® and TWYNEO®, in terms of percentage change from baseline in total lesion counts and percentage change from baseline in inflammatory and non-inflammatory lesion counts. To date, the preliminary data also indicated that ASC40 or placebo treatment in acne patients is safe and well tolerated, and majority of treatment-related adverse events are grade 1. In the previous Phase II clinical trial of non-alcoholic steatohepatitis (NASH) patients with 12-week treatment of 50 mg ASC40 once daily, 61% patients showed 30% relative decrease of liver fat. The current Phase II clinical trial is a randomized, double-blind, placebo-controlled, multicenter clinical trial in China to evaluate the safety and efficacy of ASC40 for the treatment of patients with moderate to severe acne.

180 enrolled patients have been randomized into three active treatment arms or one placebo control arm at the ratio of 1:1:1:1 to receive ASC40 (25 mg, 50 mg or 75 mg) or matching placebo orally once daily for 12 weeks. The primary outcomes include percentage change of total lesion count at week 12 compared with baseline and/or ratio of subjects, whose Investigator's Global Assessment (IGA) grades are decreased by 2 grades at week 12 compared with baseline. ASC40 is an oral, selective small molecule inhibitor of fatty acid synthase (FASN), a key enzyme which regulates de novo lipogenesis (DNL).

Human sebum production requires de novo lipogenesis, which is increased in acne and can be suppressed by the FASN inhibitor ASC40. Acne is the eighth most prevalent disease in the world and affects more than 640 million people globally. The onset of acne often coincides with pubertal hormonal changes, and the condition affects approximately 85% of adolescents and young adults aged 12 to 25 years.

However, acne can also persist into or develop during adulthood. Current first-line treatments for acne include topical creams such as topical retinoids, androgen receptor inhibitor, oral isotretinoin, and antibiotics, but still have various limitations.