Core Viewpoint - The announcement from Gilead Sciences-B (01672) highlights the successful completion of a Phase III clinical trial for the first-in-class oral small molecule fatty acid synthase (FASN) inhibitor, denifasirt (ASC40), for the treatment of moderate to severe acne, achieving all primary, key secondary, and secondary endpoints [1][6]. Group 1: Clinical Trial Results - The Phase III trial was a randomized, double-blind, placebo-controlled, multi-center study conducted in China, involving 480 patients with moderate to severe acne [1]. - The primary endpoint of treatment success was defined as a decrease of at least 2 points in the Investigator's Global Assessment (IGA) score from baseline at week 12, with a treatment success rate of 33.2% in the denifasirt group compared to 14.6% in the placebo group (p < 0.0001) [2][7]. - Key secondary endpoints showed a 57.4% reduction in total lesion count and a 63.5% reduction in inflammatory lesion count in the denifasirt group compared to 35.4% and 43.2% in the placebo group, respectively (p < 0.0001) [2][7]. Group 2: Safety and Tolerability - Denifasirt demonstrated good safety and tolerability over the 12-week treatment period, with treatment-emergent adverse events (TEAEs) occurring at rates not exceeding 10% [3]. - The only TEAEs exceeding 5% were dry skin (6.3% in the denifasirt group) and dry eye (5.9% in the denifasirt group), with all reported adverse events being mild or moderate [3]. Group 3: Mechanism of Action - Denifasirt's mechanism of action involves inhibiting de novo lipogenesis (DNL) in sebocytes, directly reducing sebum production, and suppressing inflammation through decreased cytokine secretion and Th17 differentiation [3][6]. Group 4: Competitive Advantage - Denifasirt is positioned as a promising treatment option due to its significant efficacy, high patient compliance, and favorable safety profile, with no reported severe adverse events such as hepatotoxicity or antibiotic resistance [5]. - Compared to other common oral and topical acne medications, denifasirt showed superior efficacy, with treatment success rates and lesion count reductions significantly higher than those of sarecycline, doxycycline, and clascoterone [4][9].