Long-term use of the fatty acid synthase (FASN) inhibitor denifanstat maintains its clinical efficacy in patients with moderate-to-severe acne without compromising their safety, according to a phase III extension study (ASC40-304) presented at EADV 2026.
“Denifanstat 50 mg once daily for up to 52 weeks demonstrated a favourable safety profile and sustained clinical efficacy in moderate-to-severe acne, with no drug-related serious or grade ≥3 adverse events and continued improvement in Investigator’s Global Assessment (IGA) response and lesion counts during long-term treatment,” wrote lead author Dr Qinyi Chen, Huashan Hospital, Fudan University, Shanghai, China, and colleagues.
Denifanstat had initially demonstrated its efficacy and safety in the randomized, double-blind, placebo-controlled phase III ASC40-303 trial.
A total of 240 patients participated in this multicentre, open-label phase III extension study. Only those who completed the ASC40-303 trial were eligible for enrolment after screening and written informed consent. Participants then received once-daily oral denifanstat 50 mg for up to 40 weeks of additional treatment (total exposure up to 52 weeks) after completing the 12-week double-blind period and study unblinding. Long-term safety was the primary endpoint, and efficacy was the secondary endpoint.
Of the eligible patients with moderate-to-severe acne, 116 received denifanstat during both the double-blind and extension phases (one patient did not receive the study drug), and 124 switched to denifanstat from placebo (safety population, n=239).
Safety profile
Using the ASC40-303 baseline, treatment-emergent adverse events (TEAEs) occurred in 196 patients (82.0 percent), and treatment-emergent serious adverse events (TESAEs) in only two (0.8 percent). Five participants (2.1 percent) had temporary treatment interruption, with no permanent discontinuations. Treatment-related TESAEs or grade ≥3 TEAEs did not occur. Dry akin (7.1 percent) was the most common treatment-related adverse event, followed by dry eye disease (5.9 percent). [EADV 2026, abstract 1057]
For the extension period (ASC40-304 baseline), TEAEs occurred in 156 patients (65.3 percent), with no treatment-related TESAEs, grade ≥3 TEAEs, or treatment discontinuations due to adverse events.
Use of denifanstat for 52 weeks did not increase the incidence of selected mild (grade 1-2) treatment-related adverse events, including dry eye disease, dry skin, and skin desquamation (coded as skin exfoliation), with additional low-frequency (≥1 percent and ≥5 percent) mild TEAEs compared with the 12-week ASC40-303 treatment period.
“Compared with 12-week treatment, longer exposure was associated with slightly higher rates of selected mild treatment-related adverse events and the emergence of new mild TEAEs,” Chen and colleagues said.
Efficacy
Treatment success, defined as an IGA score of 0 or 1 with at least a 2-point improvement, occurred in 67 patients (57.8 percent) who continued using denifanstat and in 69 participants (55.6 percent) who switched from placebo, suggesting sustained improvement in both groups over 52 weeks. Seventy-two (62.1 percent) and 74 (59.7 percent) patients, respectively, achieved IGA reduction of ≥2 points.
Furthermore, the mean total lesion decreased by 73.0 percent and 70.7 percent in the continuous denifanstat and switch groups. The mean inflammatory lesion count fell by 78.1 percent and 75.8 percent, and the mean noninflammatory lesion count dropped by 68.3 percent and 65.5 percent, respectively.