Denifanstat Sustains Acne Control Through 52 Weeks, With Neal Bhatia, MD

Full 52-week results from a phase 3 open-label extension trial show denifanstat, an oral fatty acid synthase (FASN) inhibitor, maintained acne control with a favorable long-term safety profile in patients with moderate to severe acne vulgaris, according to Neal Bhatia, MD, director of clinical dermatology at Therapeutics Clinical Research in San Diego. The data, from the ASC40-304 extension study conducted by Ascletis BioScience in China, were presented as a poster today at the European Academy of Dermatology and Venereology (EADV) Congress 2026 in Vienna, Austria, building on the 12-week pivotal phase 3 results reported last year. Bhatia discussed the findings in an interview with HCPLive.

Denifanstat, also known as ASC40 in China, is not an antibiotic or a retinoid; instead, it inhibits fatty acid synthase, the enzyme central to sebum production.

"It's more effective to turn off the faucet than mop up the mess," Bhatia said, explaining that by limiting sebum, the drug also curbs the inflammatory mediators and the food source for Cutibacterium acnes that sebum helps sustain.

The extension study enrolled 239 patients in its safety population, 115 who remained on continuous denifanstat and 124 who switched from placebo to denifanstat after the 12-week double-blind period.¹ Bhatia noted the 2 groups diverged somewhat in baseline disease severity entering the extension, with the placebo-switch group starting with more severe disease. Treatment success, defined as an Investigator's Global Assessment score of 0 or 1 with at least a 2-point improvement, was achieved by 57.8% of patients who remained on denifanstat throughout and 55.6% of those who switched from placebo, reflecting continued improvement in both groups over the full 52 weeks.¹ Bhatia said reductions were seen not just in inflammatory lesion counts but in comedone counts as well, and that efficacy generally plateaued between weeks 24 and 36.

On safety, Bhatia said the extension data addressed his top concerns as an investigator directly. "There were very few serious adverse events. Only two that were counted in one of the groups, and nobody discontinued the drug for any adverse events," he said.

The most frequently reported treatment-related events, dry skin, dry eye, and skin desquamation, were low-frequency and did not lead to treatment discontinuation.¹ Bhatia said the absence of retinoid-like or antibiotic-like adverse effects reflects the drug's targeted mechanism, and that no laboratory monitoring is required, a meaningful distinction from options such as spironolactone.

Looking ahead, Bhatia said the 52-week safety data support long-term use of denifanstat as a maintenance therapy alongside topical treatment, potentially reducing reliance on antibiotics and, in some patients, spironolactone, without positioning the drug as a replacement for isotretinoin. He said remaining questions include optimal use in combination regimens, tapering strategies, and dosing flexibility, which he expects to be addressed as the drug moves toward a planned US phase 3 program.

Bhatia’s disclosures include Asclestis, Sagimet, Sanofi/Regeneron, Sun Pharmaceutical Industries, Soligenix, Takeda, Zerigo Health, and more.

References

1. Denifanstat for moderate-to-severe acne vulgaris: results from an open-label, multicenter, phase III extension study. Poster presented at: European Academy of Dermatology and Venereology (EADV) Congress 2026; September 30-October 3, 2026; Vienna, Austria.

2. Sagimet Biosciences Inc. Sagimet announces positive full 52-week results from license partner Ascletis' phase 3 open-label extension clinical trial of denifanstat in acne presented at EADV 2026. Published September 30, 2026. https://www.globenewswire.com/news-release/2026/09/30/3371663/0/en/sagimet-announces-positive-full-52-week-results-from-license-partner-ascletis-phase-3-open-label-extension-clinical-trial-of-denifanstat-in-acne-presented-at-eadv-2026.html