Ascletis' Acne Drug Denifanstat Scores Phase 3 Win, Poised for Chinese Regulatory Push

Ascletis Pharma has announced positive results from a phase 3 trial of its oral acne treatment, denifanstat, positioning the company for a potential regulatory submission in China. The once-daily pill demonstrated significant efficacy in treating moderate to severe acne vulgaris, potentially offering a new oral option in a market dominated by topical treatments.

Phase 3 Trial Results

The Chinese study enrolled 480 patients with moderate to severe acne vulgaris, randomizing them to receive either a 50-mg daily dose of denifanstat or placebo for 12 weeks. The trial met all three of its primary endpoints:

• 33.2% of denifanstat-treated patients achieved clear or almost clear skin at Week 12, compared to 14.6% on placebo, representing an 18.6% placebo-adjusted increase in treatment success.
• Average reduction in total skin lesions was 57.4% for denifanstat versus 35.4% for placebo.
• Inflammatory lesions decreased by 63.5% in the denifanstat group compared to 43.2% in the placebo group.

Ascletis CEO Jinzi Jason Wu expressed enthusiasm about the results, stating, "Denifanstat tablets demonstrated impressive efficacy beyond treatment success, showing significant reductions in total lesion count, inflammatory lesion count, and non-inflammatory lesion count."

Competitive Landscape and Mechanism of Action

While the trial was not designed for direct comparisons, Ascletis presented denifanstat's 18.6% placebo-adjusted treatment success alongside historical data from competitors. This included Almirall's Seysara (9.4%), doxycycline (6.7%), and clascoterone cream (11.6%).

Denifanstat, a fatty acid synthase inhibitor, works by decreasing cytokine secretion to inhibit facial sebum production, a root cause of acne. This mechanism differentiates it from antibiotics like tetracyclines, potentially avoiding issues of antibiotic resistance and certain off-target effects.

Safety Profile and Next Steps

The safety profile of denifanstat was reported to be similar to placebo, with dry skin and dry eye being the only treatment-related adverse events affecting slightly more than 5% of patients in the denifanstat arm.

Ascletis is now preparing to submit denifanstat for approval to the China National Medical Products Administration. The company views the drug as a potential first-in-class, once-daily oral acne treatment that could offer both high efficacy and patient compliance.

Originally licensed from Sagimet Biosciences in 2019 for exploration in liver disease, denifanstat now represents a significant opportunity for Ascletis in the dermatology space, aligning with the company's recent pivot towards metabolic diseases.