Efficacy and Safety of Clascoterone Cream 1% and Adapalene Gel 0.3% in Patients With Acne

Acne vulgaris is among the most common dermatologic conditions worldwide.^1,2 Acne typically begins during adolescence and may persist into adulthood, particularly in women.^3-5 Acne vulgaris is characterized by hyperseborrhea, noninflammatory lesions (open and closed comedones), and inflammatory lesions (papules-pustules, nodules, and cysts), most often affecting the face and trunk.^3,5,6 The pathophysiology of acne is multifactorial, involving excess sebum production, follicular hyperkeratinization, Cutibacterium acnes colonization, and inflammation.^7-13 Sebum production is largely regulated by androgens such as testosterone and 5α-dihydrotestosterone, which bind to androgen receptors in sebocytes and activate gene expression that drives lipogenesis and sebocyte differentiation.¹⁴ The resulting excess sebum triggers downstream pathways that culminate in lesion formation.¹⁵

Clascoterone cream 1% is a first-in-class topical androgen receptor inhibitor approved for the treatment of acne vulgaris in patients 12 years of age and older.¹⁶ In two Phase 3 trials (NCT02608450 and NCT02608476), clascoterone cream 1% monotherapy demonstrated superior efficacy vs vehicle, significantly reducing acne severity and lesion counts, and showed a favorable safety profile, which was maintained during up to 9 months of treatment in an extension safety study.^17,18 Although no studies have fully characterized the mechanism of action of clascoterone cream 1%,¹⁶ evidence from in vitro studies suggests that it competes with dihydrotestosterone to bind to androgen receptors and inhibits downstream androgen-regulated sebum production and associated inflammatory pathways.^19,20 Consistent with this, treatment with clascoterone cream 1% for 12 weeks significantly reduced casual facial sebum levels in patients with mild-to-moderate acne.²¹