Ascletis Pharma Inc. (HKEX: 1672) presented Phase III results of denifanstat (ASC40) in moderate to severe acne vulgaris at the EADV Congress 2025 in Paris.
The data were featured in the Late Breaking News sessions on September 17, 2025.
Oral Presentation Details
- Title: First-in-Class FASN Inhibitor Denifanstat Achieved All Endpoints in Acne Vulgaris: Results from a Phase III Randomised Placebo-Controlled Trial.
- Presenter: Dr. Leihong (Flora) Xiang, Principal Investigator, Huashan Hospital, Fudan University.
The Phase III study was a randomized, double-blind, placebo-controlled, multicenter trial in China with 480 patients.
Participants received either 50 mg denifanstat once daily or placebo for 12 weeks, with a 1:1 randomization ratio. Baseline characteristics were balanced across groups.
Trial Endpoints
Primary endpoints:
- Treatment success (IGA score 0 or 1, with ≥2-point improvement).
- Percent reduction in total lesion count (TLC).
- Percent reduction in inflammatory lesion count (ILC).
Key secondary endpoint:
- Percent reduction in non-inflammatory lesion count (NILC).
Secondary endpoints:
- Absolute reduction in TLC.
- Absolute reduction in ILC.
Efficacy Results
Significant improvements appeared by Week 4 in treatment success, TLC, ILC, and NILC.
At Week 12, denifanstat (ASC40) met all primary, key secondary, and secondary endpoints (ITT analysis).
Table 1. Efficacy Results (Denifanstat vs. Placebo)
|
Endpoint |
Denifanstat (%) |
Placebo (%) |
Difference |
p-value |
|
Treatment success |
33.17 |
14.58 |
18.59 |
<0.0001 |
|
TLC Reduction |
57.38 |
35.42 |
21.96 |
<0.0001 |
|
ILC reduction |
63.45 |
43.21 |
20.24 |
<0.0001 |
|
NILC reduction |
51.85 |
28.94 |
22.91 |
<0.0001 |
|
Absolute TLC reduction |
58.25 |
36.17 |
22.08 |
<0.0001 |
|
Absolute ILC reduction |
26.56 |
18.42 |
8.14 |
<0.0001 |
Safety and Tolerability
Denifanstat demonstrated a favorable safety profile after 12 weeks.
- TEAEs: 58.6% (denifanstat) vs. 56.3% (placebo).
- No TEAE category exceeded 10% incidence.
- Only two categories crossed 5% incidence: dry skin (6.3% vs. 2.9%) and xerophthalmia (5.9% vs. 3.8%).
- Most TEAEs were mild (Grade 1) or moderate (Grade 2).
- No Grade 3/4 drug-related TEAEs.
- No drug-related SAEs, deaths, or permanent discontinuations.
Next Steps
- Pre-NDA consultation with China’s NMPA is ongoing, with encouraging feedback.
- NDA submission for acne treatment is planned following consultation.
Leadership Commentary
“Denifanstat represents a new mechanism for acne treatment,” said Dr. Jinzi Jason Wu, Founder, Chairman, and CEO of Ascletis.
“It achieved statistically significant and clinically meaningful results across all endpoints, with a favorable safety profile.”
About Denifanstat (ASC40)
- A first-in-class fatty acid synthase (FASN) inhibitor.
- Licensed from Sagimet Biosciences Inc. (Nasdaq: SGMT) for exclusive Greater China rights.
- Designed as a once-daily oral tablet for acne vulgaris.
About Ascletis Pharma Inc.
Ascletis is a biotechnology company developing best-in-class and first-in-class drugs for metabolic diseases.
Key platforms:
- AISBDD (AI-Assisted Structure-Based Drug Discovery).
- ULAP (Ultra-Long-Acting Platform).
Lead program: ASC30, an oral and injectable GLP-1R agonist for chronic weight management.
Ascletis is listed on the Hong Kong Stock Exchange (1672.HK).
