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
Ascletis presented successful Phase III clinical trial results for denifanstat (ASC40), a first-in-class FASN inhibitor for acne treatment, at EADV Congress 2025. The trial, involving 480 patients with moderate to severe acne vulgaris, demonstrated that denifanstat met all primary, key secondary, and secondary efficacy endpoints.
Key achievements include 33.17% treatment success versus 14.58% for placebo, 57.38% reduction in total lesion count, and 63.45% reduction in inflammatory lesions. The drug showed a favorable safety profile, with TEAEs comparable to placebo (58.6% vs 56.3%). Ascletis plans to submit an NDA to China's NMPA following encouraging pre-NDA consultation feedback.
Ascletis ha presentato i risultati di fase III di successo per denifanstat (ASC40), un inibitore FASN di prima classe per il trattamento dell'acne, al Congresso EADV 2025. Lo studio, che ha coinvolto 480 pazienti con acne vulgaris da moderata a grave, ha dimostrato che denifanstat ha raggiunto tutti gli endpoint primari, secondari chiave ed efficaci secondari.
Tra i principali traguardi: 33,17% di successo terapeutico rispetto al 14,58% del placebo, riduzione del 57,38% del conteggio totale delle lesioni e riduzione del 63,45% delle lesioni infiammatorie. Il profilo di sicurezza è stato favorevole, con TEAE paragonabili al placebo (58,6% vs 56,3%). Ascletis intende presentare una NDA alla NMPA cinese dopo feedback incoraggiante dalla consultazione pre-NDA.
Ascletis presentó resultados exitosos de fase III para denifanstat (ASC40), un inhibidor FASN de primera clase para el tratamiento del acné, en el Congreso EADV 2025. El ensayo, que incluyó 480 pacientes con acné vulgar moderado a severo, demostró que denifanstat cumplió todos los endpoints primarios, secundarios clave y secundarios de eficacia.
Entre los logros: 33,17% de éxito terapéutico frente al 14,58% de placebo, reducción del 57,38% en el conteo total de lesiones y reducción del 63,45% en las lesiones inflamatorias. El fármaco presentó un perfil de seguridad favorable, con TEAE comparables al placebo (58,6% vs 56,3%). Ascletis planea presentar una NDA ante la NMPA china tras comentarios alentadores de la consulta previa a la NDA.
Ascletis가 denifanstat (ASC40)의 3상 임상 성공 결과를 acne 치료를 위한 최초의 FASN 억제제로 EADV Congress 2025에서 발표했습니다. 중등도에서 중증의 여드름 vulgaris를 가진 480명의 환자를 대상으로 한 이 연구는 denifanstat가 모든 주요 1차, 핵심 2차 및 2차 효능 엔드포인트를 달성했음을 보여주었습니다.
주요 성과로는 위약 대비 치료 성공률 33.17%, 총 병변 수 57.38% 감소, 염증성 병변 63.45% 감소가 있습니다. 안전성 프로필도 우수했으며 TEAE는 위약과 유사하게 나타났습니다(58.6% vs 56.3%). Ascletis는 Pre-NDA 상담 피드백이 고무적이라는 점에 따라 중국 NMPA에 NDA를 제출할 계획입니다.
Ascletis a présenté des résultats réussis de phase III pour le denifanstat (ASC40), un inhibiteur FASN de première classe pour le traitement de l'acné, au Congrès EADV 2025. L'essai, portant sur 480 patients atteints d'acné vulgaris modérée à sévère, a démontré que le denifanstat a atteint tous les critères d'efficacité primaires, secondaires clés et secondaires.
Réalisations clés : 33,17% de succès thérapeutique contre 14,58% pour le placebo, réduction de 57,38% du nombre total de lésions et réduction de 63,45% des lésions inflammatoires. Le profil de sécurité est favorable, les TEAE étant comparables au placebo (58,6% vs 56,3%). Ascletis prévoit de déposer une NDA auprès de la NMPA chinoise après les retours encourageants de la consultation pré-NDA.
Ascletis präsentierte auf dem EADV-Kongress 2025 Ergebnisse der Phase-III-Studie für Denifanstat (ASC40), einen First-in-Class-FASN-Inhibitor zur Behandlung von Akne. Die Studie mit 480 Patienten mit mittelschwerer bis schwerer Akne vulgaris zeigte, dass Denifanstat alle primären, wichtigen sekundären und sekundären Endpunkte erreichte.
Zu den wichtigsten Ergebnissen gehören eine Behandlungserfolg-Rate von 33,17% gegenüber 14,58% Placebo, eine 36,38%ige Reduktion der Gesamtläsionszahl (Hinweis: hier korrigiert zu 57,38%), und eine 63,45% Reduktion der entzündlichen Läsionen. Das Sicherheitsprofil war günstig, TEAEs vergleichbar mit Placebo (58,6% vs 56,3%). Ascletis plant, nach ermutigendem Feedback aus der Pre-NDA-Beratung, eine NDA bei der chinesischen NMPA einzureichen.
قدمت شركة Ascletis نتائج ناجحة من تجربة المرحلة الثالثة لمركب denifanstat (ASC40)، وهو مثبِّط FASN من فئة أولى لعلاج حب الشباب، في مؤتمر EADV 2025. اشتملت الدراسة على 480 مريضاً مصاباً بحب الشباب المعتدل إلى الشديد، وأظهرت أن denifanstat حقق جميع نقاط النهاية الأولية والفرعية الأساسية والثانوية.
من الإنجازات الرئيسية: 33.17% نجاح في العلاج مقابل 14.58% وِعْد Placebo، خفض 57.38% في إجمالي عدد الآفات، وخفض 63.45% في الآفات الالتهابية. أظهر الدواء ملف سلامة جيد، مع TEAEs مشابهة للوهمي (58.6% مقابل 56.3%). تخطط Ascletis لتقديم NDA لدى NMPA الصينية بعد التعليقات المشجّعة من الاستشارة المسبقة لـ NDA.
Ascletis 在 EADV 2025 大会公布了 denifanstat (ASC40) 的 III 期临床试验的成功结果，这是用于治疗痤疮的首创 FASN 抑制剂。该研究涉及 480 例中重度痤疮患者，结果显示 denifanstat 达到了所有主要、关键次要及次要终点。
主要成就包括 33.17% 的治疗成功率对比 安慰剂 14.58%、总病变数下降 57.38%、炎性病变下降 63.45%。安全性资料良好，TEAE 与安慰剂相当（58.6% vs 56.3%）。Ascletis 计划在预 NDA 咨询反馈积极后向中国药监局 NMPA 提交 NDA。
- Met all primary, key secondary and secondary efficacy endpoints in Phase III trial
- Achieved 33.17% treatment success rate vs 14.58% for placebo
- Demonstrated significant lesion count reductions: 57.38% in total lesions and 63.45% in inflammatory lesions
- Showed favorable safety profile with mostly mild to moderate adverse events
- Received encouraging feedback from NMPA during pre-NDA consultation
- Higher incidence of dry skin (6.3% vs 2.9%) and xerophthalmia (5.9% vs 3.8%) compared to placebo
- Overall TEAEs rate slightly higher than placebo (58.6% vs 56.3%)
Insights
Sagimet's partner reported strong Phase III results for denifanstat in acne, advancing toward potential China approval with a novel mechanism of action.
Ascletis Pharma has presented compelling Phase III data for denifanstat (ASC40) at the EADV Congress, demonstrating significant efficacy for moderate-to-severe acne treatment. As a first-in-class FASN inhibitor, denifanstat represents a novel mechanism of action in the acne treatment landscape. The drug met all primary endpoints with impressive statistical significance - achieving 33.17% treatment success versus 14.58% for placebo, a 57.38% reduction in total lesions versus 35.42% for placebo, and a 63.45% reduction in inflammatory lesions versus 43.21% for placebo.
Importantly, the safety profile appears favorable, with adverse events comparable to placebo (58.6% versus 56.3%) and primarily mild-to-moderate severity. The most common treatment-related effects were dry skin (6.3%) and xerophthalmia (5.9%), typical side effects for many dermatological treatments.
For Sagimet Biosciences (SGMT), which licensed Greater China rights to Ascletis, these results significantly de-risk their asset. Regulatory progress appears on track, with encouraging feedback from China's NMPA during pre-NDA consultations. This positions denifanstat for potential near-term commercialization in the substantial Chinese acne market.
The novel mechanism targeting fatty acid synthesis could differentiate denifanstat from current acne treatments that primarily target bacteria, inflammation, or keratin production. This represents a potentially valuable addition to Sagimet's pipeline, which also includes applications of this compound for other indications including metabolic-associated steatohepatitis (MASH).
--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:
--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.
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
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:
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
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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