Targeting Sebum at the Source: Neal Bhatia, MD, on the Promise of Denifanstat

“Dermatologists should be excited to await the approach of a new oral therapy for acne that isn't a retinoid or an antibiotic,” Neal Bhatia, MD, said in this interview with Dermatology Times.

Bhatia, director of clinical dermatology at Therapeutics Clinical Research in San Diego, California, discussed the clinical significance of denifanstat, a late-stage oral investigational therapy for acne that targets sebum production through inhibition of fatty acid synthase (FASN). Bhatia emphasized that this mechanism represents a major departure from traditional systemic acne therapies, which have historically relied on antibiotics or retinoids.

By inhibiting de novo lipogenesis, denifanstat reduces sebum not simply as surface oil, but as a key metabolic fuel that drives inflammation, comedogenesis, and downstream acne pathogenesis. According to Bhatia, this distinction is critical: targeting sebum biology rather than oiliness alone positions FASN inhibition as a potentially disease-modifying strategy. The availability of an oral, non-antibiotic, non-retinoid option could meaningfully expand therapeutic choices, particularly in an era of antibiotic stewardship and ongoing safety concerns surrounding isotretinoin.

Safety and tolerability data emerging from recent clinical trials have been encouraging. Bhatia notes that denifanstat has demonstrated a favorable adverse event profile compared with existing systemic therapies for moderate to severe acne. Reported adverse effects—such as mild skin dryness and minor ocular symptoms—were generally well tolerated and did not lead to treatment discontinuation. This tolerability profile may address key barriers that currently limit clinician and patient acceptance of oral acne therapies.

Efficacy findings from a 52-week phase 3 program conducted in China further support the drug’s potential. In a randomized study of 480 patients with moderate-to-severe acne, once-daily denifanstat achieved substantial reductions in total lesion counts (approximately 58%), inflammatory lesions (around 63%), and comedonal lesions (about 50%). Importantly, a meaningful proportion of patients reached clear or almost clear status, with sustained benefit observed through one year of treatment. These results build upon earlier 12-week data and suggest durability of response with long-term use.

Bhatia identifies patients who are poor candidates for antibiotics or isotretinoin due to safety concerns, resistance issues, or regulatory barriers as particularly well suited for this approach. Looking ahead, he underscores the need for large, well-controlled trials in North America to confirm efficacy across diverse populations and practice settings. Such studies will be essential to defining denifanstat’s role within the US acne treatment landscape and further validating FASN inhibition as a novel systemic strategy.

“We'll get more demographics, some more age groups, more skin of color, more variation of presentations, and also some numbers that we can really relate to our current treatment landscape in the US,” Bhatia noted about future research.