Denifanstat achieved 56.7% treatment success and reduced total acne lesions by 71.8% in a 52-week Phase 3 extension study reported by Sagimet and Ascletis.
Written By: Khushi Patel, PharmD
Reviewed By: Pharmacally Editorial Team
Sagimet Biosciences and its Chinese licensing partner Ascletis reported sustained improvements in moderate to severe acne with denifanstat, an oral fatty acid synthase (FASN) inhibitor, in a Phase 3 open-label extension study. At 52 weeks, 56.7% of patients achieved treatment success, while total and inflammatory skin lesions declined by 71.8% and 76.9%, respectively.
Phase 3 Extension Shows Sustained Efficacy
The results from the ASC40-304 open-label extension (OLE) trial (NCT06248008) were presented at the 2026 European Academy of Dermatology and Venereology (EADV) Congress in Vienna. The study evaluated the long-term safety of denifanstat in patients with moderate to severe acne vulgaris who had previously participated in the 12-week, randomized, placebo-controlled Phase 3 ASC40-303 trial in China.
A total of 240 patients entered the extension study, including 116 who had received denifanstat and 124 who had initially received placebo. Participants received denifanstat 50 mg once daily for up to another 40 weeks, allowing those originally assigned to active treatment to receive up to 52 weeks of exposure.
At the end of the extension, the overall treatment success rate was 56.7%. Treatment success required at least a two-point improvement in the Investigator’s Global Assessment (IGA) score, reaching clear or almost-clear skin.
Patients who received denifanstat during both study periods achieved a 57.8% treatment success rate, compared with 55.6% among those who switched from placebo to denifanstat.
Mean total lesion counts declined by 71.8% from the original Phase 3 baseline. Inflammatory lesions decreased by 76.9%, while non-inflammatory lesions fell by 66.9%. These findings indicate that improvements observed during the initial treatment period were maintained or extended with longer exposure.
FASN Inhibition Offers a Different Treatment Approach
Denifanstat is an oral, once-daily small-molecule inhibitor of fatty acid synthase, an enzyme involved in the production of fatty acids, including palmitate. By inhibiting FASN, the drug targets lipid metabolism, a pathway implicated in acne development.
Moderate to severe acne can require prolonged management, and patients may need repeated courses of treatment to control flare-ups. Denifanstat’s oral administration and distinct mechanism could provide another treatment option if clinical development and regulatory review establish its safety and efficacy.
Ascletis holds the exclusive license to develop denifanstat, marketed as ASC40 in its development program, for acne in China. Sagimet is responsible for development in the rest of the world.
Long-Term Safety Findings
Denifanstat was generally well tolerated during the extension study. No patients permanently discontinued treatment because of adverse events, and investigators reported no drug-related serious adverse events among patients treated with denifanstat.
Dry skin was reported in 7.1% of patients and dry eye in 5.9%. These were the only treatment-related adverse-event categories with an incidence above 5% during the 52-week period.
Although the findings support longer-term tolerability, the open-label design and absence of a continuing placebo control limit comparisons of treatment effects against untreated disease over the extension period.
U.S. Phase 3 AURORA Trial Next
Sagimet plans to advance denifanstat through its U.S. AURORA Phase 3 program, with patient screening expected to begin in October 2026 and first enrollment anticipated shortly afterward.
The trial is expected to enroll approximately 800 patients aged 12 years and older, including around 450 adolescents aged 12 to 17 years. Participants will be randomized in a 2:1 ratio to receive denifanstat 50 mg once daily or placebo for 12 weeks.
The study will assess three co-primary endpoints at Week 12: IGA treatment success, change in inflammatory lesion counts, and change in non-inflammatory lesion counts. Approximately 530 participants completing the double-blind period may enter a further 40-week open-label extension to evaluate long-term safety.
The 52-week findings from China provide additional evidence supporting denifanstat’s continued development. However, its clinical benefit and safety in the broader U.S. population, including adolescents, will depend on the results of the planned Phase 3 program.
Reference
Sagimet To Present Positive Full 52-Week Results from License Partner Ascletis’ Phase 3 Open-Label Extension Clinical Trial of Denifanstat in Acne and Mechanistic Data at the 2026 Fall Clinical Dermatology Conference, Sagimet Bioscience, 09 October 2026
A Study to Evaluate Safety of ASC40 Tablets in Patients with Moderate to Severe Acne Vulgaris, ClinicalTrials.gov ID NCT06248008
About the Writer
Khushi Patel is a Pharm.D (Linkedin) professional with a strong foundation in clinical pharmacy, patient-centered care, regulatory affairs, and pharmacovigilance, with published work on Brugada syndrome.
Her interests include regulatory affairs, pharmacovigilance, guideline integration, multimodal therapy, pharmacogenomics, and antibiogram utilization, with a focus on evidence-based clinical decision-making and medication safety.
As a Pharmacally healthcare writer, she translates clinical and scientific evidence into clear, accurate, and clinically relevant healthcare content, while continuously developing her expertise in evolving pharmacy practice.