Sagimet: Positive Phase 3 Results for Denifanstat in Acne Treatment by Ascletis

Sagimet Biosciences Inc., a clinical-stage biopharmaceutical company, recently highlighted significant advancements in their research on acne treatment. Their drug candidate, denifanstat, has successfully met all primary and secondary endpoints in a Phase 3 clinical trial focused on moderate to severe acne vulgaris. This trial was conducted by Ascletis Bioscience Co. Ltd., Sagimet's partner in China. Denifanstat is an oral fatty acid synthase (FASN) inhibitor that is administered once daily and is being developed in China under the name ASC40 for acne, while Sagimet is exploring its use for metabolic dysfunction-associated steatohepatitis (MASH) globally.

David Happel, Sagimet’s CEO, noted the encouraging results of the Phase 3 trial, emphasizing the potential of FASN inhibition as an innovative approach to treating moderate to severe acne. Acne vulgaris affects over 640 million individuals worldwide, and these findings bolster the development of another FASN inhibitor, TVB-3567, intended for the U.S. market. Dr. Neal Bhatia, a prominent clinical dermatologist, expressed excitement over the progress of this novel oral treatment, especially given the stagnation in acne therapeutic innovation over the past four decades. Dr. Bhatia highlighted the importance of addressing the overproduction of sebum and inflammation, which are key acne pathways, through a new mechanism of action. He further stressed the urgent need for such treatments due to limitations in existing acne therapies related to efficacy, irritation, and antibiotic resistance.

Acne is exceedingly common in the United States, affecting over 50 million individuals annually. The pathogenesis of acne vulgaris is driven partly by increased sebum production compared to non-acne populations, which results from enhanced de novo lipogenesis (DNL) in sebocytes. The FASN enzyme plays a crucial role in DNL by producing essential sebum lipids like palmitate and sapienic acid, and also contributes to inflammatory pathways. Thus, inhibiting FASN is considered a promising therapeutic strategy for acne. In earlier Phase 1 trials, Sagimet used a non-invasive approach to assess FASN activity by collecting sebum. These trials demonstrated significant reductions in sapienic acid, a sebum fatty acid unique to DNL, thereby confirming the effectiveness of FASN inhibition.

The Phase 3 trial was rigorously designed as a randomized, double-blind, placebo-controlled study across multiple centers in China. It aimed to assess the safety and efficacy of denifanstat among patients with moderate to severe acne. A total of 480 participants were equally randomized into two groups receiving either denifanstat 50 mg or a placebo, administered daily for 12 weeks. The primary endpoints included treatment success, measured by a decrease in the Investigator’s Global Assessment (IGA) score, alongside changes in total and inflammatory lesion counts. Ascletis reported that denifanstat successfully met all these endpoints.

Denifanstat was generally well-tolerated, with treatment-emergent adverse events (TEAEs) occurring at similar rates in both the drug and placebo groups. Notably, the incidence rates of denifanstat-related adverse events did not exceed 10%, and were predominantly mild or moderate, with no serious adverse events reported. On the strength of these positive Phase 3 results, Ascletis plans to submit denifanstat for approval to the China National Medical Products Administration. Meanwhile, Sagimet is advancing its research by initiating a Phase 1 clinical trial for TVB-3567, another oral FASN inhibitor aimed at treating acne in the U.S., building upon the success of denifanstat.

Sagimet Biosciences continues to develop innovative treatments targeting metabolic and fibrotic pathways, with denifanstat leading their efforts in addressing conditions like MASH. Their ongoing trials and research aim to bring novel solutions to the widespread issue of acne, offering hope for improved management and outcomes for millions affected by this skin condition.