F Xiang, et al. Abstract #LBA-213. Presented at: European Academy of Dermatology and Venereology Congress; Sept. 17-20, 2025; Paris.
Denifanstat, a fatty acid synthase inhibitor, has been shown to be effective in treating moderate to severe acne vulgaris and has also demonstrated excellent safety and good tolerability.
Once-daily oral administration of denifanstat, a fatty acid synthase inhibitor, improved moderate to severe acne vulgaris compared with placebo after 4 weeks of treatment.
The molecule can directly inhibit fatty acid synthesis in sebocytes and can also block inflammation by reducing cytokine release and suppressing T-helper 17 cell differentiation. The authors conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of denifanstat compared to placebo in the treatment of moderate to severe acne vulgaris. In the study, 480 participants (mean age 22.6 years; 68.8% female) were randomly assigned to receive denifanstat 50 mg (n = 240) or placebo (n = 240) once daily for 12 weeks. At baseline, the mean number of inflammatory and non-inflammatory lesions in participants was 42.6 and 59.5, respectively; 85.8% of participants had an IGA score of 3.
The primary endpoints were an IGA score of clear or almost clear with a decrease of at least 2 points in the IGA from baseline at week 12, defined as treatment success, and a percentage reduction from baseline at week 12 in the total number of lesions and inflammatory lesions. The key secondary endpoint was a percentage reduction in the number of non-inflammatory lesions.
Alla settimana 12, l’analisi intention-to-treat ha mostrato che il 33,17% dei partecipanti trattati con denifanstat ha raggiunto il successo del trattamento rispetto al 14,58% di coloro che hanno ricevuto placebo, con una differenza tra i gruppi del 18,59% (IC al 95%, 15,58% – 21,61%; P < 0,0001).
I pazienti trattati con denifanstat hanno inoltre ottenuto una riduzione del 57,38% rispetto al basale del numero totale di lesioni rispetto al 35,42% di quelli trattati con placebo, con una differenza intergruppo del -21,96% (IC al 95%, da -27,51% a -16,40%; P < 0,0001). Il gruppo denifanstat ha inoltre osservato una maggiore riduzione delle lesioni infiammatorie (63,45%) rispetto al gruppo placebo (43,21%), con una differenza del -20,24% tra i gruppi (IC al 95%, da -26,21% a -14,27%; P < 0,0001).
Inoltre, i pazienti trattati con denifanstat hanno ottenuto una riduzione del 51,85% rispetto al basale nella conta delle lesioni non infiammatorie, rispetto a una riduzione del 28,94% osservata nel gruppo placebo (differenza = -22,91%; IC al 95%, da -30,02% a -15,8%; P < 0,0001). Già dalla quarta settimana, i pazienti trattati con denifanstat hanno mostrato miglioramenti maggiori in diversi endpoint di efficacia rispetto ai pazienti trattati con placebo, secondo la presentazione (P < 0,05).
Adverse events that emerged during treatment, most of which were mild and moderate, occurred in 58.6% and 56.3% of patients treated with denifanstat and placebo, respectively. Adverse events related to the study drug that occurred in more than 5% of participants were dry skin (6.3% in the denifanstat group versus 2.9% in the placebo group) and dry eyes (5.9% in the denifanstat group versus 3.8% in the placebo group). No serious adverse events were reported.