Gelonghui May 2nd 丨Geli Pharmaceutical-B (01672.HK) announced that the first-of-its-kind, once-a-day, oral fatty acid synthase (FASN) inhibitor ASC40 (Denifanstat) for acne phase II clinical trial has reached the primary and critical secondary endpoints. ASC40 is an oral, selective small molecule FASN inhibitor. The mechanism of ASC40 in treating acne is: (1) directly inhibits facial sebum production by inhibiting fatty acid synthesis (DNL) of human sebaceous cells from scratch; and (2) inhibits inflammation by reducing cytokine secretion and Th17 differentiation.

The phase II study is a randomized, double-blind, placebo-controlled, multi-center clinical trial conducted in China to evaluate the safety and efficacy of ASC40 in treating patients with moderate to severe acne. The 180 patients enrolled were randomly distributed in a 1:1:1:1 ratio into three active drug groups and a placebo control group, and received oral ASC40 (25 mg, 50 mg, or 75 mg) or placebo treatment once daily for 12 weeks. Of these, 179 patients took ASC40 or placebo at least once.

ASC40 is safe and well tolerated at all doses taken orally once daily for 12 weeks. The incidence of experimental drug-related adverse events was similar for 25 mg (grade 1 = 28.9%; grade 2 = 20.0%), 50 mg (grade 1 = 36.4%; grade 2 = 11.4%), 75 mg (grade 1 = 44.4%; grade 2 = 17.8%) ASC40 and placebo (grade 1 = 35.6%; grade 2 = 13.3%). Among all treatment groups, the most common adverse event associated with the experimental drug was eye dryness, with a similar incidence in 25 mg (grade 1 = 17.8%; grade 2 = 6.6%), 50 mg (grade 1 = 22.7%; grade 2 = 2.3%), 75 mg (grade 1 = 15.5%; grade 2 = 11.1%), ASC40 and placebo (grade 1 = 28.9%; grade 2 = 6.6%). There were no grade 3 and 4 adverse events associated with ASC40, and no serious adverse events associated with ASC40. No deaths have been reported.

Based on efficacy and safety evaluations, taking 50 mg orally once a day is the recommended dose for phase III clinical trials. The phase III clinical trial is expected to commence in the second half of 2023. The evaluation of whether the other two doses are those of the phase III trial is still ongoing. In the previous phase IIa clinical trial to treat patients with non-alcoholic steatohepatitis (NASH), 50 mg of ASC40 was taken orally, once a day, after 12 weeks of administration, 61% of patients showed clinically significant and statistically significant reduction in liver fat. Additionally, statistically significant reductions in total cholesterol, low-density lipoprotein cholesterol (LDL-C), and alanine aminotransferase (ALT) /alanine aminotransferase (AST) were observed at week 12.

Acne is the 8th most common disease worldwide, affecting more than 640 million people worldwide. Adherence to topical treatments is lower than oral medications: it is estimated that around 30% to 40% of patients fail to complete topical treatment as directed by their doctor. Currently, effective oral acne medications are mainly isotretinoin, which may cause many serious adverse events such as liver toxicity, hearing impairment, and depression. ASC40 is expected to be the first oral acne drug of its kind, once a day, with remarkable curative effects, high patient compliance, and good safety.