Phase II Results: ASC40 FASN Inhibitor for Acne Presented at AAD 2024

A recent study has shed light on the potential of a novel acne treatment. The research, conducted by Ascletis Pharma Inc., a biotech firm listed on the Hong Kong Stock Exchange, focused on ASC40, a groundbreaking inhibitor of fatty acid synthase (FASN). The Phase II clinical trial's final results were highlighted at the 2024 American Academy of Dermatology (AAD) Annual Meeting, showcasing the drug's effectiveness and safety profile in treating acne vulgaris.
The trial, designated as NCT05104125, was a multicenter, randomized, double-blind, and placebo-controlled study involving 180 participants. The participants were evenly distributed across four groups receiving either a placebo or ASC40 at dosages of 25, 50, or 75 mg once daily (QD) for a period of 12 weeks, followed by a 2-week follow-up period. The study's primary objectives were to evaluate the efficacy and safety of ASC40 in comparison to the placebo.
ASC40, also known as denifanstat, operates through a unique dual mechanism. It directly curbs facial sebum production by inhibiting de novo lipogenesis (DNL) in sebocytes and also mitigates inflammation by reducing cytokine secretion. Prior research had already demonstrated that ASC40 could significantly lower facial sebum palmitic acid levels after a 10-day treatment period. The Phase II study aimed to assess the drug's long-term efficacy and safety over a 12-week treatment duration in patients with moderate to severe acne.
The study's findings were encouraging, with improvements in efficacy measures observed from the second week through to the twelfth week across all dosages. The 50 mg QD dosage emerged as the most effective, with a placebo-adjusted success rate and Investigator's Global Assessment (IGA) reduction of 14.3% and 16.2%, respectively. The median percentage change from baseline in total lesion and inflammatory counts was -27.1% (-23.5) and -33.5% (-13), respectively, with statistical significance (p-values of 0.008 and 0.003).
In terms of safety, the incidence rates of adverse events (AEs) related to the study drug were similar across the ASC40 dosages and the placebo group. Dry eyes were the most frequently reported AE, with comparable rates across all ASC40 dosages and the placebo. Importantly, there were no clinically significant findings in clinical laboratory tests, vital signs, or electrocardiography. Additionally, there were no grade 3 or 4 AEs or serious AEs (SAEs) attributed to ASC40.
Given the positive outcomes, a Phase III clinical trial for ASC40 has been initiated, focusing on the 50 mg QD dosage for a 12-week treatment period. Dr. Jinzi J. Wu, Ascletis' Founder, Chairman, and CEO, expressed pride in presenting the Phase II results and emphasized the drug's innovative mechanism and its potential to benefit acne patients in the future. Ascletis holds the exclusive rights to develop, manufacture, and commercialize ASC40 in Greater China under a license from Sagimet Biosciences Inc.
The AAD Annual Meeting, where the results were presented, is a prestigious event in the field of dermatology, attracting leading professionals from across the United States. Ascletis, known for its innovative R&D, is also actively engaged in developing treatments for viral diseases, non-alcoholic steatohepatitis (NASH), and oncology, with a robust pipeline of drug candidates in various stages of development.