Ascletis Reports Phase 3 Success for Oral Acne Drug Denifanstat

Ascletis Pharma has announced topline results from a phase 3 clinical trial evaluating its oral fatty acid synthase inhibitor denifanstat for the treatment of moderate to severe acne vulgaris. The company reported that the trial met all three of its primary endpoints.
The randomized, placebo-controlled study included 480 patients in China. Participants received either a once-daily 50 mg dose of denifanstat or a placebo for a duration of 12 weeks. According to Ascletis, 33.2% of patients treated with denifanstat were assessed as having clear or almost clear skin at Week 12, compared to 14.6% of patients in the placebo group. The company reported an 18.6% placebo-adjusted increase in treatment success.

In addition, the average reduction in total skin lesions was 57.4% in the denifanstat group and 35.4% in the placebo group. For inflammatory lesions, the reduction was 63.5% among patients receiving denifanstat, compared to 43.2% in the placebo cohort.
Although the trial was not designed for direct comparison with other acne therapies, Ascletis presented the results alongside previously reported data for Seysara, doxycycline, and clascoterone cream. Based on these comparisons, the placebo-adjusted treatment success rates were 9.4% for Seysara, 6.7% for doxycycline, and 11.6% for clascoterone cream.
The company stated that denifanstat has a safety and tolerability profile similar to that of a placebo. The only treatment-related adverse events that occurred in slightly more than 5% of patients in the denifanstat group were dry skin and dry eye.
Denifanstat is designed to reduce the production of facial sebum by decreasing cytokine secretion. Ascletis noted that this mechanism does not involve antibiotics and does not carry risks associated with antibiotic resistance or off-target effects of tetracycline antibiotics.
Ascletis CEO Jinzi Jason Wu, Ph.D., stated, “We are extremely pleased with the topline results of our phase 3 trial.” He added that denifanstat showed significant reductions in total, inflammatory, and non-inflammatory lesion counts and confirmed the company’s plan to submit the treatment to the China National Medical Products Administration.
Ascletis obtained the China rights to denifanstat from Sagimet Biosciences in 2019. The original objective was to explore the drug’s application in metabolic dysfunction-associated steatohepatitis. As of March, the company indicated that it would make further assessments to identify opportunities for the program.

Ascletis, which went public in 2018, originally focused on antiviral, cancer, and liver disease candidates. Following clinical setbacks in its core areas, including the discontinuation of hepatitis B and liver disease programs, the company has recently introduced a weight loss pipeline featuring oral and subcutaneous formulations of a GLP-1 receptor agonist. Earlier this year, Ascletis formalized its strategic shift toward metabolic disease.