Denifanstat for moderate-to-severe acne: A Phase 2, randomized, double-blind, placebo-controlled trial.

BACKGROUND

Acne vulgaris is a common chronic inflammatory skin disease with largely unmet treatment needs.

PATIENTS AND

METHODS

This was a multi-centre, randomized, double-blind, placebo-controlled, dose-escalation Phase 2 trial (Clinicaltrials.gov ID: NCT05104125) to evaluate the safety, tolerability and efficacy of denifanstat, a first-in-class fatty acid synthase inhibitor, in patients with moderate-to-severe acne vulgaris. Denifanstat was administered orally at 25 (n = 45), 50 (n = 44), 75 (n = 45) mg or placebo (n = 45) once daily after dinner for 12 weeks.

RESULTS

Denifanstat was generally well-tolerated. Study drug-related TEAEs were 48.9% (22/45), 47.7% (21/44), 62.2% (28/45) and 48.9% (22/45) in the denifanstat 25, 50 and 75 mg and placebo groups, respectively. The most common TEAEs were dry eye, dry skin, urine protein positive, skin peeling and conjunctivitis (Grade 1 to 2). No serious drug-related TEAEs occurred. At Week 12, denifanstat demonstrated significantly greater median reductions in total lesion counts versus placebo (25 mg: -53.2% [Q1-Q3: -62.5% to -37.6%]; 50 mg: -61.3% [-78.2% to -29.1%]; 75 mg: -53.1% [-62.4% to -39.2%] vs. placebo: -34.2% [-53.0% to -18.4%]; all p < 0.05). The proportion of participants achieving a ≥ 2-grade reduction in Investigator's Global Assessment (IGA) for denifanstat 25, 50 and 75 mg and placebo was 31.1% (14/45), 31.8% (14/44), 22.2% (10/45) and 15.6% (7/45), respectively. The difference among the four groups was not significant (p = 0.336).

CONCLUSIONS

Denifanstat 50 mg once daily for 12 weeks was generally well tolerated and showed potential to reduce total lesion counts in moderate-to-severe acne vulgaris. Larger and longer term studies are needed to confirm efficacy and safety.