Denifanstat Hits All Targets in Chinese Study

Image Credit: © DermNet

Today, Ascletis Pharma has announced promising phase 3 trial results for denifanstat (ASC40), its oral fatty acid synthase (FASN) inhibitor, in the treatment of moderate to severe acne vulgaris. The randomized, double-blind, placebo-controlled study conducted in China enrolled 480 patients and met all primary and secondary efficacy end points. These findings mark a significant milestone for Ascletis and its US-based development partner Sagimet Biosciences, potentially paving the way for regulatory submission in China.¹

“It is very exciting to see this novel oral acne product candidate progressing through development in light of the limited innovation within the acne space over the past 40 years,” Neal Bhatia, MD, director of clinical dermatology at Therapeutics Clinical Research in San Diego, California, and a past vice president of the American Academy of Dermatology, said in a news release. “These data demonstrate the significant clinical response that a FASN inhibitor can achieve for moderate to severe acne patients by addressing the overproduction of sebum and the inflammatory cascade, 2 of the primary pathways of acne, and most importantly, through a novel mechanism of action. With currently available treatments either showing limited efficacy, high potential for irritation, or risks of antibiotic resistance, control of acne through new modes of action is more critical now than ever.”

Denifanstat, originally developed by Sagimet and in-licensed by Ascletis for rights in Greater China, was administered once daily over a 12-week treatment period. The primary end point—treatment success as defined by an Investigator’s Global Assessment score of 0 (clear) or 1 (almost clear), with a minimum 2-point improvement from baseline—was achieved by 33.2% of patients in the denifanstat group compared with 14.6% in the placebo group. This statistically significant difference highlights the drug's therapeutic benefit in reducing the clinical severity of acne.

Additional primary outcomes included marked improvements in lesion counts. Total lesion count was reduced by 57.4% in the denifanstat group compared with a 35.4% reduction in the placebo group. Inflammatory lesion counts dropped by 63.5% in the denifanstat arm vs 43.2% with placebo. A key secondary end point also revealed a 51.9% reduction in noninflammatory lesion counts with denifanstat, significantly outperforming the 28.9% reduction seen in the placebo group.

“We are highly encouraged by the positive results from Ascletis’ phase 3 acne trial in China,” David Happel, chief executive officer of Sagimet, said in a news release. “FASN inhibition represents a novel potential approach to treat moderate to severe acne vulgaris, a widespread condition impacting more than 640 million people worldwide. These positive data support the rationale for our development of our FASN inhibitor TVB-3567 for moderate to severe acne and add to the body of evidence of the broad consequences of unchecked overactivity of FASN.”

Safety data from the trial were also favorable. Treatment-emergent adverse events (AEs) were similar between the denifanstat and placebo groups, with all AEs rated as mild or moderate. Notably, there were no grade 3 or 4 treatment-related AEs, serious AEs, or deaths attributed to the investigational drug.

Denifanstat’s therapeutic potential appears to extend beyond dermatology. It is currently being evaluated for metabolic dysfunction–associated steatohepatitis in the FASCINATE-2 phase 2b study, which has completed patient enrollment. Results from liver biopsies and additional end points are anticipated in the first quarter of 2024. Furthermore, denifanstat is under investigation in a phase 3 study combined with bevacizumab for the treatment of recurrent glioblastoma, with Ascletis having enrolled 120 patients for an interim analysis focused on progression-free survival.² 

FASN is a key enzyme involved in de novo lipogenesis, a metabolic process linked to several conditions, including acne, cancer, and liver disease. By selectively targeting this pathway, denifanstat may offer a new mechanism of action in dermatologic and systemic disease management.

With positive data in multiple therapeutic areas and a favorable safety profile, denifanstat stands as a potential first-in-class oral treatment for acne and a promising candidate in the growing field of metabolic and oncologic disorders. Regulatory submission in China will be a pivotal next step in determining the drug’s future in clinical practice.

References

1. Sagimet Biosciences announces positive phase 3 results for denifanstat for the treatment of moderate-to-severe acne from partner ascletis. News release. Sagimet Biosciences. June 4, 2025. Accessed June 4, 2025. https://ir.sagimet.com/news-releases/news-release-details/sagimet-biosciences-announces-positive-phase-3-results
2. Sagimet Biosciences announces completion of enrollment of 120 patients for phase 3 clinical trial by its partner ascletis of denifanstat combined with bevacizumab for treatment of recurrent glioblastoma. News release. Sagimet Biosciences. September 27, 2023. Accessed June 4, 2025. https://ir.sagimet.com/node/7116/pdf