Ascletis Completes Enrollment of Phase III Trial of ASC40 (Denifanstat) Once-Daily Oral Tablet for Treatment of Acne

Rhea-AI Summary

Ascletis Pharma has completed enrollment of 480 patients in its Phase III clinical trial of ASC40 (denifanstat), a once-daily oral tablet for treating moderate to severe acne. The randomized, double-blind, placebo-controlled trial began on January 24, 2024, with patients divided equally between treatment and placebo groups. The study will evaluate 50 mg ASC40 over 12 weeks, with topline results expected in Q2 2025.

ASC40 is a first-in-class FASN inhibitor that works by inhibiting facial sebum production and reducing inflammation. The Phase II trial previously met primary and secondary endpoints with 19.4% of patients achieving treatment success versus 5.1% for placebo.

Positive

• Phase III trial successfully completed enrollment target of 480 patients
• Previous Phase II trial met primary and secondary endpoints with 19.4% treatment success vs 5.1% placebo
• Novel first-in-class drug mechanism with dual action on sebum production and inflammation

Negative

• Topline results not available until Q2 2025
• Phase II showed relatively low absolute treatment success rate of 19.4%

Insights

Medical Research Analyst

The completion of Phase III enrollment for ASC40 (denifanstat) marks a significant milestone in acne treatment development. The 480-patient trial is well-designed with proper randomization and controls, evaluating a novel mechanism of action through FASN inhibition. The previous Phase II results showing 19.4% treatment success versus 5.1% placebo are encouraging, though modest compared to existing treatments.

The dual mechanism targeting both sebum production and inflammation through DNL inhibition represents an innovative approach. However, investors should note that the Q2 2025 timeline for topline results means a considerable wait before potential commercialization. The Chinese market focus also limits immediate global market potential, though success could lead to expanded trials internationally.

-Phase III trial enrolled a total of 480 patients with moderate to severe acne
-Topline results expected in the second quarter 2025

HANGZHOU, China, Nov. 12, 2024 /PRNewswire/ -- Ascletis Pharma Inc. (HKEX: 1672, "Ascletis") today announces completion of enrollment of 480 patients for Phase III clinical trial of ASC40 (denifanstat) once-daily oral tablet for treatment of moderate to severe acne. The first patient was enrolled on January 24, 2024.

This Phase III clinical trial is a randomized, double-blind, placebo-controlled, multicenter clinical trial in China to evaluate the safety and efficacy of ASC40 once-daily oral tablet for the treatment of moderate to severe acne vulgaris. 480 patients with moderate to severe acne vulgaris were enrolled and randomized into one active treatment arm and one placebo control arm at the ratio of 1:1 to receive 50 mg ASC40 oral tablet once daily or matching placebo for 12 weeks. Topline results are expected in the second quarter 2025.

The primary efficacy endpoints are the proportion of patients achieving treatment success at week 12, the percentage change from baseline in total lesion count at week 12, and the percentage change from baseline in inflammatory lesion count at week 12. Treatment success is defined as at least a 2-point reduction in Investigator's Global Assessment (IGA) score from baseline and a score of clear (0) or almost clear (1).

On May 2, 2023, Ascletis announced that the Phase II clinical trial for ASC40 once-daily oral tablet for the treatment of acne vulgaris met the primary and key secondary endpoints, demonstrating superior efficacy including 19.4% patients achieving treatment success at week 12 versus placebo (5.1%) and a good safety profile (Link).

ASC40 is a first-in-class, once-daily oral, selective small molecule inhibitor of fatty acid synthase (FASN). Mechanisms of ASC40 for treatment of acne are (1) direct inhibition of facial sebum production through inhibition of de novo lipogenesis (DNL) in human sebocytes, and (2) inhibition of inflammation through decreasing cytokine secretion and Th17 differentiation.  ASC40 is licensed from Sagimet Biosciences Inc. (Nasdaq: SGMT) for exclusive rights in Greater China.

"As a first-in-class once-daily oral drug candidate with novel mechanism for acne treatment, ASC40 has shown positive efficacy and a good safety profile in the Phase II study. We look forward to announcing topline results of the ASC40 (denifanstat) Phase III trial in the second quarter 2025." said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis.

About Ascletis Pharma Inc.

Ascletis is an innovative R&D driven biotech listed on the Hong Kong Stock Exchange (1672.HK), covering the entire value chain from discovery and development to GMP manufacturing. Led by a management team with deep expertise and a proven track record, Ascletis has rapidly advanced its pipeline, focusing on two therapeutic areas with unmet medical needs from a global perspective: metabolic diseases and viral diseases. Ascletis has multiple clinical stage drug candidates in its R&D pipeline.

For more information, please visit www.ascletis.com.

Contact：
Peter Vozzo
ICR Healthcare
443-231-0505 (U.S.)
Peter.vozzo@westwicke.com

Ascletis Pharma Inc. PR and IR teams
+86-181-0650-9129 (China)
pr@ascletis.com
ir@ascletis.com

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SOURCE Ascletis Pharma Inc.

FAQ

What are the primary endpoints for ASC40's Phase III acne trial?

The primary endpoints are: proportion of patients achieving treatment success at week 12, percentage change in total lesion count, and percentage change in inflammatory lesion count. Treatment success means at least a 2-point reduction in IGA score and a score of clear (0) or almost clear (1).

How many patients were enrolled in ASC40's Phase III acne trial?

480 patients with moderate to severe acne were enrolled and randomized equally between the treatment arm (50 mg ASC40) and placebo control arm.

What was ASC40's treatment success rate in Phase II acne trials?

In Phase II trials, ASC40 achieved a 19.4% treatment success rate at week 12, compared to 5.1% for placebo.

How does ASC40 (denifanstat) work in treating acne?

ASC40 works through two mechanisms: inhibiting facial sebum production by blocking de novo lipogenesis in human sebocytes, and reducing inflammation by decreasing cytokine secretion and Th17 differentiation.