Topical clascoterone cream 1% (also known by its brand name, Winlevi®) represents the first breakthrough in acne treatment in years and functions as a novel solution to targeting the androgen component of acne. Clascoterone is the first topical agent ever Food and Drug Administration (FDA)-approved that modulates sebum production in acne patients.8 As the first topical androgen inhibitor available for use in both men and women, clascoterone avoids the systemic adverse effects of other anti-androgen medications such as OCPs and spironolactone, and exists as a promising treatment option since receiving FDA approval for treatment of acne vulgaris in patients 12 years old and older in 2020.6,13,14
Mechanism of Action
Clascoterone, also known as cortexolone-17α propionate, is an ester derivative of cortexolone and an androgen receptor inhibitor that shares a 4-ring backbone with the androgen dihydrotestosterone (DHT) and the androgen receptor inhibitor spironolactone.8,9,12,13 Clascoterone functions as an androgen receptor inhibitor to counteract the effects of the androgenic effects of DHT in the skin.5,6,14
While the exact mechanism of action remains unknown, in vitro studies have shown that clascoterone competes with DHT for the androgen receptors in the sebaceous glands of hair follicles and in dermal papilla cells.6,8,9,12 DHT normally binds to androgen receptors present throughout the skin to increase sebum production from sebaceous glands and promote the development of nodular, cystic acne.6,14 By competing with DHT for androgen receptors, clascoterone prevents DHT from activating transcription of androgen-responsive genes involved in inflammatory processes, such as genes involved in both lipid synthesis and inflammatory cytokine production; this process is illustrated in Figure 1.3,6,8,9,12 As a result, less inflammation develops in the hair follicles and their associated sebaceous glands, preventing the development of acne.15 These anti-inflammatory effects of clascoterone have been shown to be dose-dependent in prior in vitro studies, and clascoterone has not been found to be toxic to sebocyte cultures at the concentration needed to exhibit the above effects.8,12 Additionally, in vitro studies have shown that clascoterone binds and inhibits androgen receptors with an even greater affinity than spironolactone.12 Excretion of clascoterone has not been extensively studied in studies thus far.16
Notably, clascoterone is quickly hydrolyzed to its inactive metabolite, cortexolone, by esterases located in the epidermis, so the activity of this medication is highly localized to the area of its topical application.6,8,10,15,17
Efficacy
The prior clinical trials evaluating clascoterone cream are listed in Table 1. Early studies have demonstrated that clascoterone is an effective treatment for acne. For example, Trifu et al conducted a phase I clinical trial that showed that clascoterone worked faster and was better tolerated than tretinoin 0.05% or vehicle cream in adult men with moderate to severe facial acne.18
A 2019 phase II clinical trial evaluated the safety and efficacy of clascoterone at concentrations 0.1%, 0.5%, and 1% compared with placebo to determine the optimal concentration and dosing regimen.19 Treatment efficacy was measured by changes in the inflammatory lesion count (ILC), non-inflammatory lesion count (NILC), Investigator’s Global Assessment (IGA), and patient satisfaction with treatment.19 Treatment success was defined as achieving an IGA score of 0 or 1 ("clear" or "almost clear") and an improvement from baseline by 2 or more IGA grades.19
This study demonstrated that clascoterone at concentrations of 0.1%, 0.5%, or 1% all led to significantly greater treatment success after 12 weeks than the placebo cream in 363 male and female patients 12 years and older with acne vulgaris.19 Treatment success was highest for patients using clascoterone 1% BID and 0.1% BID, with a success rate of 8.6% and 8.3%, respectively, compared with 2.7% in patients using placebo cream.19 The clascoterone treatment
