Clinical Pharmacology and Safety of Trifarotene, a First-in-Class RARγ-Selective Topical Retinoid

Area of Science:

• Dermatology
• Pharmacology
• Clinical Science

Background:

• Trifarotene is a novel topical retinoid targeting the retinoic acid receptor-gamma (RAR-γ).
• Acne vulgaris is a common skin condition requiring effective and safe treatment options.

Purpose of the Study:

• To assess the clinical pharmacology and safety profile of topical trifarotene in acne patients.
• To evaluate systemic absorption, cardiovascular safety, and drug-drug interactions of trifarotene.

Main Methods:

• Pharmacokinetic trials (MUsT) in adult and pediatric acne patients.
• Thorough QT/QTc study and drug-drug interaction study with oral contraceptives in healthy volunteers.
• Safety assessments included local tolerability and systemic laboratory testing.

Main Results:

• Trifarotene showed minimal systemic absorption, particularly at the intended 50 µg/g dose.
• No cardiovascular risks were identified in the QT/QTc study.
• Trifarotene did not affect the systemic exposure of oral contraceptives (levonorgestrel/ethinyl estradiol).
• Local and systemic safety assessments revealed no significant concerns, even at supratherapeutic doses (100 µg/g).

Conclusions:

• Topical trifarotene 50 µg/g cream is well-tolerated and safe for treating moderate to severe acne in adults and pediatric patients.
• Daily use of trifarotene is not associated with cardiovascular effects or drug-drug interactions in women using oral contraception.