Individual Article: Clascoterone Cream 1%: Mechanism of Action, Efficacy, and Safety of a Novel, First-in-Class Topical Antiandrogen Therapy for Acne
June 2023 | Volume 22 | Issue 6 | SF350992s7 | Copyright © June 2023
Published online May 31, 2023
Hannah Peterson BSa, Leon Kircik MDb,c, April W. Armstrong MD MPHd
aLoma Linda University School of Medicine, Loma Linda, CA
bIcahn School of Medicine at Mount Sinai, New York, NY; Indiana University Medical Center, Indianapolis, IN;
Physicians Skin Care, PLLC Louisville, KY; DermResearch, PLLC Louisville, KY; Skin Sciences, PLLC Louisville, KY
cIndiana University Medical Center, Indianapolis, IN
dDepartment of Dermatology, Keck School of Medicine of University of Southern California, Los Angeles, CA
Abstract
Acne is a prevalent chronic inflammatory disease that can cause severe psychiatric effects and physical scarring of the skin. Historically, although systemic antiandrogen acne medications have been effective in women, the utility of these systemic medications has been limited due to potential systemic side effects in men and pregnant women. Therefore, research has been focused on developing topical formulations of antiandrogen therapy for acne. Topical clascoterone cream 1% is the first topical anti-androgen medication approved for the treatment of acne vulgaris in patients 12 years and older and represents a breakthrough in acne treatment.
Clascoterone, or cortexolone-17α propionate, is an androgen receptor inhibitor with highly localized activity. Thismedication is thought to compete with dihydrotestosterone (DHT) for androgen receptors located in pilosebaceous units, thus inhibiting the acnegenic downstream effects of DHT such as lipid synthesis and inflammatory cytokine production in a dose-dependent manner. Two phase III clinical trials have been conducted thus far; both trials have shown clascoterone 1% cream applied BID to be significantly more effective than placebo cream at treating acne vulgaris in patients ages 12 and older with moderate-to-severe acne. Clascoterone has also been shown to have a similar safety profile to that of placebo cream in clinical studies, without any systemic antiandrogenic effects observed in the clinical setting. Due to its novel mechanism of action and activity limited to the skin, clascoterone presents an exciting opportunity for dermatologists to further optimize care for eligible acne patients, either as a monotherapy or in combination with other anti-acne medications.
J Drugs Dermatol. 2023;22:56(Suppl 1):s7-14.
INTRODUCTION
Acne is a prevalent chronic inflammatory disease that causes both severe psychiatric effects and physical scarring of the skin.1-4 The 4 pathogenetic pathways that contribute to this condition are increased sebum production, inflammation, colonization by Cutibacterium acnes, and hyperkeratinization.1,5 Acne treatment regimens can be topical or systemic, and they target one or more of these pathogenic pathways.1 Examples of topical medications include retinoids, antibiotics, and salicylic acid, while systemic medications include isotretinoin, antibiotics, and combined oral contraceptive pills (OCPs).1 However, no major breakthroughs in acne therapy have occurred since the introduction of isotretinoin in 1982, and current treatments are not without their shortcomings.2,6 For example, while isotretinoin is effective and generally well-tolerated, its teratogenic properties make it complicated to prescribe and
