Denifanstat Sustains Acne Improvement Through 52 Weeks in Phase 3 Extension

Denifanstat, an oral fatty acid synthase (FASN) inhibitor, produced continued improvement across all efficacy endpoints through 52 weeks in patients with moderate to severe acne vulgaris, according to phase 3 open-label extension data presented at the 2026 Fall Clinical Dermatology Conference in Las Vegas, Nevada.¹,²

The 52-week results come from the ASC40-304 trial, conducted in China by Ascletis BioScience, Sagimet Biosciences’ license partner. Julie Harper, MD, founding director and past president of the American Acne and Rosacea Society, of the Dermatology and Skin Care Center of Birmingham in Birmingham, Alabama, presented them alongside preclinical mechanistic data.² The National Medical Products Administration accepted Ascletis’ new drug application for denifanstat in China in December 2025.¹

“The data being presented at the Fall Clinical Dermatology Conference highlight the potential and novel role of FASN inhibition to treat patients and families living with acne,” David Happel, chief executive officer of Sagimet, said in a statement. “Denifanstat has demonstrated significant and sustained improvements in moderate to severe acne through 52 weeks of treatment.”¹

What Did the ASC40-304 Extension Show for Denifanstat in Acne?

ASC40-304 (NCT06248008) was a multicenter, open-label phase 3 extension of the 12-week randomized, double-blind, placebo-controlled ASC40-303 trial (NCT06192264).¹ In ASC40-303, 480 patients with moderate to severe acne vulgaris were randomized 1:1 to denifanstat 50 mg or placebo once daily. Denifanstat met all primary and secondary endpoints in the parent trial, according to Sagimet.¹

A total of 240 patients rolled over into the extension and received oral denifanstat 50 mg once daily for up to 40 weeks, including 116 originally randomized to denifanstat and 124 originally randomized to placebo.¹ Patients initially assigned to denifanstat accrued up to 52 weeks of total exposure. Safety was the primary endpoint. The secondary efficacy endpoints were Investigator’s Global Assessment (IGA) success and reductions in total and inflammatory lesion counts from baseline.

Through 52 weeks, denifanstat produced 57% IGA success, a 72% reduction in total lesion count, and a 77% reduction in inflammatory lesion count, according to the company.¹ Improvements across all efficacy endpoints extended beyond those observed at Week 12. Sagimet reported denifanstat was generally well tolerated throughout the extension period.¹

How Does FASN Inhibition Target Acne Pathogenesis?

Harper’s presentation also reviewed mechanistic evidence supporting FASN as a therapeutic target in acne.² FASN inhibition reduced sebum lipids in human sebocytes in vitro and in clinical trial participants in vivo, according to the presentation highlights.¹

In the 12-week placebo-controlled trial, denifanstat significantly improved IGA scores and reduced lesion counts compared with placebo, with significant improvements observed as early as Week 4.¹ These clinical gains continued through 52 weeks of treatment in the extension.

According to the presenters, the clinical findings and preclinical data together support FASN inhibition as a novel oral approach to acne. It targets key aspects of acne pathogenesis, including de novo lipogenesis, sebum production, and inflammation.¹,² Ascletis is developing denifanstat as ASC40 in China, where it holds an exclusive license, and Sagimet is developing it in the rest of the world.¹

In the US, Sagimet has activated sites and begun screening patients for AURORA (NCT07863193), a randomized, double-blind, placebo-controlled phase 3 trial. The trial is expected to enroll approximately 800 patients aged 12 years and older, including about 450 adolescents aged 12 to 17 years.¹ Patients will be randomized 2:1 to denifanstat 50 mg or placebo once daily for 12 weeks. The co-primary endpoints are global assessment treatment success, absolute change in inflammatory lesion count, and absolute change in noninflammatory lesion count. Approximately 530 patients who complete the double-blind period will be eligible for a 40-week open-label safety extension.¹

Editor's Note: This summary has been edited for grammar and clarity using artificial intelligence tools.

References

1. Sagimet Biosciences. Sagimet to present positive full 52-week results from license partner Ascletis’ phase 3 open-label extension clinical trial of denifanstat in acne and mechanistic data at the 2026 Fall Clinical Dermatology Conference. Published October 9, 2026. Accessed October 11, 2026. https://www.globenewswire.com/news-release/2026/10/09/3377993/0/en/sagimet-to-present-positive-full-52-week-results-from-license-partner-ascletis-phase-3-open-label-extension-clinical-trial-of-denifanstat-in-acne-and-mechanistic-data-at-the-2026-f.html.

2. Harper J. Denifanstat, a fatty acid synthase inhibitor, achieved significant clinical improvement in moderate-to-severe acne vulgaris: a review of mechanistic and clinical data. Presented at: 2026 Fall Clinical Dermatology Conference; October 8-11, 2026; Las Vegas, NV.