Ascletis Presents Positive Phase 3 Data for Denifanstat in Moderate to Severe Acne

At the 2025 European Academy of Dermatology and Venereology Congress in Paris, France, Ascletis Pharma Inc. presented late-breaking results from a Phase 3 clinical trial evaluating the efficacy and safety of denifanstat (ASC40), a first-in-class fatty acid synthase (FASN) inhibitor, for the treatment of moderate-to-severe acne vulgaris.¹ The findings were presented by Leihong (Flora) Xiang, MD, PhD, principal investigator of the study and member of the Department of Dermatology at Huashan Hospital, Fudan University in Shanghai, China.²

Trial Design and Endpoints

The Phase 3 trial (NCT06192264) was a randomized, double-blind, placebo-controlled, multicenter study conducted in China. A total of 480 patients with moderate to severe acne were randomized 1:1 to receive either 50 mg of denifanstat orally once daily or placebo for 12 weeks. More than 68% of the total participants were female with a mean age of 22.6 years. Approximately 85.8% of the group began the trial with Grade 3 disease (moderate) while 14.2% started with Grade 4 (severe).

The study’s primary endpoints included Investigator’s Global Assessment (IGA) success (IGA score of 0 or 1 and ≥2-point reduction from baseline), the percent reduction in total lesion count (TLC), and the percent reduction in inflammatory lesion count (ILC) at week 12. Key secondary endpoints included the percent reduction in non-inflammatory lesion count (NILC), while additional secondary endpoints focused on absolute reductions in TLC and ILC.

Efficacy Results

Denifanstat met all primary, key secondary, and secondary endpoints, with results demonstrating both statistical and clinical significance compared to placebo. Notably, treatment effects were evident as early as week 4. At week 12, the denifanstat group saw higher levels of IGA treatment success compared to placebo (33.17% versus 14.58%, p < 0.0001). Reductions were observed in TLC (57.38%), ILC (63.45%), and NILC (51.85%). These were all statistically significant and greater than placebo.

Safety Profile

Denifanstat also demonstrated a favorable safety and tolerability profile. The incidence of treatment-emergent adverse events was comparable between the treatment and placebo groups (58.6% vs. 56.3%). Most adverse effects were mild (Grade 1) or moderate (Grade 2), and no treatment-related or Grade 3/ 4 drug-related serious adverse events were observed. The most commonly reported ones included dry skin (6.3% denifanstat versus 2.9% placebo) and xerophthalmia (5.9% denifanstat versus 3.8% placebo). No treatment discontinuations occurred.

Next Steps

Ascletis is currently completing Pre-New Drug Application (NDA) consultations with the China National Medical Products Administration (NMPA) in hopes of submitting an NDA soon. According to the company, the feedback received from the NMPA has been encouraging, making this first-in-class agent targeting lipid metabolism a potentially valuable option in the acne treatment landscape.

"Denifanstat (ASC40) is an innovative and potentially meaningful advancement for the treatment of acne and we're very pleased that we have presented these results to the dermatology community at this year's EADV Congress," founder, chairman, and CEO of Ascletis, Jinzi Jason Wu, PhD, said in a statement. "Denifanstat (ASC40) has a new mechanism of action for acne treatment and demonstrated statistically significant and clinically meaningful improvement compared to placebo in all primary and secondary endpoints in the Phase 3 study, as well as a favorable safety and tolerability profile."¹

References

1. Ascletis Presented Phase III Study Results of First-in-Class FASN Inhibitor Denifanstat (ASC40) for Acne Treatment in the Late Breaking News Sessions of the European Academy of Dermatology and Venereology (EADV) Congress 2025. News release. PR Newswire. Published September 17, 2025. Accessed September 18, 2025. https://www.prnewswire.com/news-releases/ascletis-presented-phase-iii-study-results-of-first-in-class-fasn-inhibitor-denifanstat-asc40-for-acne-treatment-in-the-late-breaking-news-sessions-of-the-european-academy-of-dermatology-and-venereology-eadv-congress-2025-302559228.html

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.