Androgens and acne: perspectives on clascoterone, the first topical androgen receptor antagonist

ABSTRACT

Introduction: Increased circulating androgens are key to the multifactorial pathogenesis of acne. Clascoterone is the first topical androgen antagonist developed to treat acne in both male and female patients and the first such agent to receive U.S. Food and Drug Administration (FDA) approval for treatment of acne. Androgens directly stimulate sebaceous gland growth and increased sebum production, creating a nourishing medium in which anaerobic Cutibacterium acnes (C. acnes) bacteria flourish. Androgens may directly contribute to inflammation in the sebaceous gland.

Areas covered: In this review, the author assesses clascoterone’s potential role in the management of acne. With a 4-ring backbone identical to dihydrotestosterone (DHT) and spironolactone, topically applied clascoterone binds androgen receptors (ARs) in the sebaceous glands and hair follicles, interfering with the pathogenesis of acne and reducing acne lesions with no reported systemic effects.

Expert opinion: Phase III study results confirmed the safety and efficacy of topical clascoterone for acne, with considerable reductions in absolute non-inflammatory and inflammatory lesion counts at week 12. The approval of a first-in-class topical androgen antagonist is indeed a ‘game-changer’ for acne management. This topical agent is expected to be quickly adopted in clinical practice, likely within combination regiments, yet to be formally evaluated.

KEYWORDS:

• Acne vulgaris
• androgen receptors
• clascoterone
• hormones/hormonal modulation
• topical therapy
• inflammatory lesions
• C. acnes

Article highlights

• Increased levels of circulating androgens contribute to acne pathogenesis through the lifecycle of affected individuals.

• Treatment strategies aimed at androgen modulation, such as oral contraceptive pills and spironolactone, have been tried. However, these treatments have only been available to women.

• Clascoterone is the first topical androgen antagonist developed to treat acne in both men and women and is the first such agent to receive FDA approval for treatment of acne.

• In Phase III clinical trials, at week 12 clascoterone met all three co-primary efficacy end points: proportion of patients achieving treatment success, absolute change from baseline in non-inflammatory lesion count (NILC), and absolute change from baseline in inflammatory lesion count (ILC).

• Only 13 treatment emergent adverse events (TEAE) were identified for clascoterone cream, 1%, in both studies. All TEAEs were mild in severity.

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Declaration of interest

LH Kircik has served as a consultant and as an advisory board member for Cassiopea. He is also the Medical Director of DermResearch, PLLC, Physicians Skin Care, PLLC and Skin Sciences PLLC. He has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This manuscript has not been funded.