New Phase 3 Data Suggest Denifanstat Effective for Moderate-to-Severe Acne

Denifanstat treatment of moderate-to-severe acne vulgaris has met all of its primary and secondary endpoints, new phase 3 findings suggest, with strong safety and tolerability.1

These findings, announced on June 4, were released by biopharmaceutical company Sagimet Biosciences Inc. The study was conducted in China by Ascletis Bioscience Co. Ltd., Sagimet’s licensee, with investigators assessing denifanstat, a once-daily oral fatty acid synthase (FASN) inhibitor that is also known as ASC40 in China.

“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, said in a statement.1 “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, two of the primary pathways of acne, and most importantly through a novel mechanism of action.”

Acne is known to be one of the most common skin conditions, impacting more than 50 million people within the US. Elevated sebum production is a well-known component of acne, driven by enhanced de novo lipogenesis (DNL) in sebocytes.

FASN, the terminal enzyme in the DNL pathway, produces more than 80% of the key sebum lipids implicated in the pathogenesis of acne and even plays a role in inflammation. As such, the use of FASN inhibition in denifanstat was explored by Ascletis Bioscience Co. and Sagimet.

Ascletis is developing denifanstat for acne within China, whereas Sagimet is advancing the treatment for patients with metabolic dysfunction-associated steatohepatitis (MASH) outside of China. Over the course of earlier phase 1 analyses, Sagimet implemented non-invasive sebum sampling to confirm that denifanstat treatment reduced levels of sapienic acid, a lipid produced exclusively through DNL, substantially.

Now, in the latest phase 3 trial (NCT06192264), the investigative team used a randomized, placebo-controlled, double-blind, multicenter trial involving 480 participants living with moderate-to-severe acne. In a 1:1 ratio, these subjects would be given either 50 mg of denifanstat or placebo on a once-daily basis over 12 weeks.

The study’s primary endpoints were the proportion of individuals attaining an Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) and at least a 2-point drop from baseline, which the team determined would define treatment success. Additionally, percentage changes in both total lesion count and inflammatory lesion count were evaluated as primary endpoints.

Overall, the study’s coauthors found that denifanstat had favorable tolerability, further noting that after 12 weeks of use, participants’ rates of treatment-emergent adverse events (TEAEs) were comparable between the denifanstat and placebo cohorts.1 They noted that there had not been any individual TEAE category exceeding 10% in incidence.

The most common TEAEs observed by the investigative team in the denifanstat arm of the study were dry skin among 6.3% and dry eye among 5.9%, versus 2.9% and 3.8% in the placebo group, respectively. All adverse events that were shown to be related to denifanstat were noted as mild or moderate, with no serious AEs and no grade 3 or 4 AEs or deaths reported.

The team highlighted that their results reinforce FASN inhibition as a novel and viable approach for treatment of acne. The announcement noted Ascletis’s plans to seek regulatory approval for denifanstat from the China National Medical Products Administration.1

“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,” Bhatia said in his statement.1

References

1. Sagimet Biosciences Announces Positive Phase 3 Results for Denifanstat for the Treatment of Moderate-to-Severe Acne from Partner Ascletis. Sagimet Biosciences Inc. June 4, 2025. https://www.globenewswire.com/news-release/2025/06/04/3093353/0/en/sagimet-biosciences-announces-positive-phase-3-results-for-denifanstat-for-the-treatment-of-moderate-to-severe-acne-from-partner-ascletis.html.