Clinical Pharmacology and Safety of Trifarotene, a First-in-Class RAR gamma-selective Topical Retinoid

Trifarotene is a new drug with retinoic acid receptor activity and selectivity for retinoic acid receptor-gamma. Trifarotene 50 µg/g cream is approved for the treatment of acne vulgaris on the face and/or trunk in adult and adolescent patients. The clinical pharmacology program aimed at assessing the clinical pharmacology and safety of trifarotene.
Systemic exposure to topically applied trifarotene up to 100 µg/g was investigated through 4 clinical studies: 2 studies were maximal usage pharmacokinetic trials (MUsT) conducted in subjects with moderate to severe acne vulgaris. The 2 other studies were conducted in healthy volunteers: 1 clinical drug-drug interaction (DDI) study and 1 thorough QTC study to assess the potential for cardiac repolarization delays. Considering the pharmacologic class of trifarotene and the class-associated potential teratogenicity, and because trifarotene is intended to be used by women of childbearing potential, a DDI study was conducted to assess the potential trifarotene effects on contraceptive steroids. Safety assessments included adverse event reporting and assessment of erythema, scaling, dryness, and stinging/burning using a scale from 0 = none to 4 = severe, as well as the evaluation of the systemic safety of trifarotene through routine laboratory testing.
Systemic absorption of trifarotene 50 µg/g cream was generally unquantifiable in adults and adolescent patients with acne vulgaris, including patients with severe acne. Daily use of trifarotene was not associated with cardiovascular effects and did not reduce the systemic exposure to oral contraceptives such as levonorgestrel or ethinyl estradiol. Safety analyses did not show local or systemic safety concerns with trifarotene up 100 µg/g, a dose twice as high as the marketed dose. The present pharmacology studies confirmed that trifarotene 50 µg/g cream is well tolerated and safe, even when applied under maximized conditions in adults and adolescent patients with acne vulgaris.