–Denifanstat (ASC40) met all primary, key secondary and secondary efficacy endpoints (ITT analysis) and significantly improved moderate-to-severe acne compared with placebo.
–Denifanstat (ASC40) demonstrated a favorable safety and tolerability profile. Treatment emergent adverse events (TEAEs) in the denifanstat (ASC40) group were comparable to placebo: 58.6% versus 56.3%. The majority of TEAEs were mild (Grade 1) or moderate (Grade 2).
–Pre-New Drug Application (NDA) consultation of denifanstat (ASC40) with the China National Medical Products Administration (NMPA) is ongoing and feedback received from NMPA so far is encouraging. Ascletis plans to submit an NDA for denifanstat (ASC40) for the treatment of moderate to severe acne vulgaris to NMPA after completing its pre-NDA consultation.
HONG KONG, Sept. 17, 2025 /PRNewswire/ — Ascletis Pharma Inc. (HKEX: 1672, “Ascletis”) announces today that the oral presentation of the Phase III study results of denifanstat (ASC40) for the treatment of moderate to severe acne vulgaris (NCT06192264) was presented in the Late Breaking News sessions of the European Academy of Dermatology and Venereology (EADV) Congress 2025 in Paris, France on September 17, 2025.
Details of the Oral Presentation
Title: First-in-Class FASN Inhibitor Denifanstat Achieved All Endpoints in the Treatment of Acne Vulgaris: Results from a Phase Ⅲ Randomised Placebo Controlled Trial
Presenter: Dr. Leihong (Flora) XIANG, M.D and Ph.D., Principal Investigator of denifanstat (ASC40) Phase III study, Department of Dermatology, Huashan Hospital, Fudan University
The Phase III clinical trial was a randomized, double-blind, placebo-controlled, multicenter clinical trial in China to evaluate the safety and efficacy of denifanstat (ASC40) once-daily oral tablet in 480 patients with moderate to severe acne vulgaris. Patients were enrolled and randomized into one active treatment arm and one placebo control arm at the ratio of 1:1 to receive 50 mg denifanstat (ASC40) oral tablet once daily or matching placebo for 12 weeks. Baseline characteristics were well balanced between denifanstat (ASC40) and placebo arms.
Primary endpoints included the percent treatment success, defined as an Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with at least a 2-point decrease in IGA from baseline at week 12, the percent reductions from baseline to week 12 in total lesion count (TLC), and the percent reduction from baseline to week 12 in inflammatory lesion count (ILC).
After 4-week treatment, the denifanstat (ASC40) group already showed statistically significant improvements (p<0.05) over placebo in multiple efficacy endpoints, including treatment success, TLC, ILC, and non-inflammatory lesion count (NILC).
After 12-week treatment, denifanstat (ASC40) met all primary, key secondary and secondary efficacy endpoints. Table 1 summarizes efficacy results from the Phase III study versus placebo (intent-to-treat, ITT analysis).
Table 1. Efficacy results from the Phase III study versus placebo (intent-to-treat, ITT analysis)
|
Efficacy endpoints (1) |
50 mg (n=240) |
Placebo, (n=240) |
Placebo adjusted
|
P value
|
|
Primary endpoints |
||||
|
Percent treatment success (2) |
33.17 |
14.58 |
18.59 |
<0.0001 |
|
Percent reduction from |
57.38 |
35.42 |
21.96 |
<0.0001 |
|
Percent reduction from |
63.45 |
43.21 |
20.24 |
<0.0001 |
|
Key secondary endpoint |
||||
|
Percent reduction from |
51.85 |
28.94 |
22.91 |
<0.0001 |
|
Secondary endpoints |
||||
|
Absolute reduction from |
58.25 |
36.17 |
22.08 |
<0.0001 |
|
Absolute reduction from |
26.56 |
18.42 |
8.14 |
<0.0001 |
|
Notes: |
|
(1) All efficacy endpoints are least square means. |
|
(2) Treatment success is defined as an Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with at least a 2-point decrease in IGA from baseline at week 12. |
|
(3) TLC: total lesion count; ILC: inflammatory lesion count; NILC: non-inflammatory lesion count. |
Denifanstat (ASC40) demonstrated a favorable safety and tolerability profile following 12 weeks of once-daily oral administration at 50 mg. The incidence rates of treatment-emergent adverse events (TEAEs) were comparable between denifanstat (ASC40) and placebo: 58.6% versus 56.3%. No incidence rates of TEAEs related to study drug in any category exceeded 10%. Only two categories of TEAEs had an incidence rate of more than 5% (6.3% dry skin in denifanstat (ASC40) -treated patients versus 2.9% in the placebo group; 5.9% xerophthalmia in denifanstat (ASC40) -treated patients versus 3.8% in the placebo group). The majority of TEAEs were mild (Grade 1) or moderate (Grade 2). All denifanstat (ASC40) -related TEAEs were mild (Grade 1) or moderate (Grade 2). There were no denifanstat (ASC40) -related Grade 3 or 4 TEAEs and no denifanstat (ASC40) -related serious AEs (SAEs). No deaths were reported. No denifanstat (ASC40) -related permanent treatment discontinuations or withdrawals were observed.
Detailed data presented at the EADV Congress 2025 can be found at Ascletis’ website (link).
“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,” said Jinzi Jason Wu, Ph.D., Founder, Chairman and CEO of Ascletis. “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 III study, as well as a favorable safety and tolerability profile.”
Pre-New Drug Application (NDA) consultation of denifanstat (ASC40) with the China National Medical Products Administration (NMPA) is ongoing and feedback received from NMPA so far is encouraging. Ascletis plans to submit an NDA for denifanstat (ASC40) for the treatment of moderate to severe acne vulgaris to NMPA after completing its pre-NDA consultation.
Ascletis licensed denifanstat (ASC40) from Sagimet Biosciences Inc. (Nasdaq: SGMT) for exclusive rights in Greater China.
About Ascletis Pharma Inc.
Ascletis Pharma Inc. is a fully integrated biotechnology company focused on the development and commercialization of potential best-in-class and first-in-class therapeutics to treat metabolic diseases. Utilizing its proprietary Artificial Intelligence-Assisted Structure-Based Drug Discovery (AISBDD) Platform and Ultra-Long-Acting Platform (ULAP), Ascletis has developed multiple drug candidates in-house, including its lead program, ASC30, a small molecule GLP-1R agonist designed to be administered once daily orally and once monthly to once quarterly subcutaneously as a treatment therapy and a maintenance therapy for chronic weight management. Ascletis is listed on the Hong Kong Stock Exchange (1672.HK).
To learn more about Ascletis, please visit www.ascletis.com.
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