Sagimet and Ascletis Report Positive 52-Week Safety and Efficacy Data for Denifanstat in Acne

This week, Sagimet Biosciences reported positive 52-week data from its license partner Ascletis Pharma’s open-label phase 3 clinical trial evaluating the long-term safety of denifanstat (ASC40) tablets in patients with moderate to severe acne vulgaris.¹ The findings further characterize the safety and sustained clinical activity of this first-in-class, once-daily oral fatty acid synthase (FASN) inhibitor, a novel therapeutic mechanism in acne.

Background and Study Design

Denifanstat is a small-molecule FASN inhibitor that targets de novo lipogenesis, a pathway implicated in sebaceous gland lipid production and acne pathophysiology. Ascletis is developing the agent as ASC40 for acne in China, while Sagimet is advancing denifanstat globally for metabolic dysfunction–associated steatohepatitis. Sagimet previously granted Ascletis an exclusive license to develop and commercialize denifanstat for acne in China.

The newly announced results derive from ASC40-304 (NCT06248008), a multicenter, open-label phase 3 extension study designed primarily to assess long-term safety. The trial enrolled 240 patients with moderate to severe acne who had completed the preceding 12-week randomized, double-blind, placebo-controlled phase 3 study (ASC40-303; NCT06192264). These results were presented at the 2025 European Academy of Dermatology and Venereology Congress in Paris, France.²

“Following the 12-week data from the phase 3 randomized double-blind denifanstat trial in moderate to severe acne patients, results from the 40-week open-label study are even more encouraging,” Neal Bhatia, MD, medical director of Therapeutics Clinical Research in San Diego, California, and former vice president of the American Academy of Dermatology, said in the press release. “For moderate to severe acne patients, who are currently underserved by older agents, the potential of a new therapeutic option would be a welcome addition to the current treatment armamentarium.”¹

In the extension, all participants received oral denifanstat 50 mg once daily for up to 40 additional weeks. Patients originally randomized to denifanstat in the parent study therefore achieved up to 52 weeks of total drug exposure. The primary endpoints of ASC40-304 focused on safety and tolerability over extended treatment, while secondary endpoints evaluated continued efficacy.

Safety Results

Overall, denifanstat was reported to be generally well tolerated. Treatment-emergent adverse events were limited in scope, with only 2 categories occurring in 5% or more of treated subjects: dry eye syndrome (5.5%) and dry skin (5.2%). These events are consistent with effects on sebaceous and related lipid pathways and were not described as leading to significant morbidity.

All denifanstat-related adverse events were characterized as mild or moderate in severity. No treatment-related Grade 3 or 4 adverse events were reported, and there were no permanent discontinuations attributed to adverse events. Hair thinning, a potential concern with agents that influence lipid metabolism, was reported in only one participant as a Grade 1 event. This resolved within 8 weeks without dose modification. Serious adverse events were infrequent and not attributed to denifanstat.

Efficacy Findings

Although the extension study was not primarily powered for efficacy, improvements across multiple clinical endpoints were observed beyond those documented at week 12 in the double-blind trial. Secondary efficacy measures included the proportion of patients achieving at least a 2-point reduction in Investigator’s Global Assessment (IGA) score, the number of patients improving from an IGA score of 3 (moderate) to 0 or 1 (clear or almost clear), percentage reduction in total lesion count, and percentage reduction in inflammatory lesion count. Patients demonstrated continued gains across these measures through longer-term therapy, suggesting durable or incremental benefit with ongoing FASN inhibition. Detailed efficacy data is expected to be presented at upcoming scientific congresses and in peer-reviewed publications.

“Sadly, the pipeline for acne treatments is drying up, and overall acne has been an underdeveloped disease market over the past 40 years,” Bhatia said in a previous interview with Dermatology Times. “For the last 10 years, dermatologists have been trying to reduce the reliance on oral antibiotics for controlling moderate to severe acne, and denifanstat seems to be a potential replacement for the over 5 million prescriptions written by dermatologists. Although the mechanisms are not the same, having another treatment option is very welcome.”

References

1. Sagimet Announces Positive 52-Week Data from License Partner Ascletis’ Open-Label Phase 3 Clinical Trial Evaluating the Long-Term Safety of ASC40 (Denifanstat) Tablets in Patients with Moderate to Severe Acne. News release. Globe Newswire. Published February 2, 2026. Accessed February 4, 2026. https://finance.yahoo.com/news/sagimet-announces-positive-52-week-120000543.html?guccounter=1&guce_referrer=aHR0cHM6Ly93d3cuZ29vZ2xlLmNvbS8&guce_referrer_sig=AQAAALzYAvR9GSc-napfsOVodYI6n8LspyzQBjtoPL43c08VuNwq41ujIyrLoL9N9UIbG-Q1n2bYjMqH5ZxPuMsEJ_wTsx4tzWgLBWi14ezl2HxAwH4GqSkt6V5iEKOkm8MBdoozpVR4tGcKI3QEjeQs9FcogXzIMpcM8sBrvEYNGfjO

2. Xiang L. First-in-class FASN inhibitor denifanstat achieved all endpoints in the treatment of acne vulgaris: results from a phase III randomised placebo controlled trial. Presented at: European Academy of Dermatology and Venereology Congress 2025; September 17-20, 2025; Paris, France.