Clascoterone Cream 1% (Winlevi)
By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved a first-in-class topical androgen receptor inhibitor for the treatment of acne vulgaris. Clascoterone cream works by binding to the androgen receptors in the sebaceous gland, thereby limiting binding of androgens, such as testosterone and dihydrotestosterone.1,2 Clascoterone is marketed as Winlevi.
Clascoterone should be prescribed to treat acne vulgaris in patients age 12 years and older.3
The recommended dose is application of approximately 1 g twice daily to affected areas.3 Clascoterone is available as a 1% cream (60-g tube).
Clascoterone provides a new mechanism of action directed at one of the pathogenesis pathways of acne. There is limited systemic exposure as opposed to oral anti-androgens (e.g., oral contraceptives, spironolactone).3
In 44 clascoterone-treated subjects (20 adults, 22 adolescents) who were evaluated after treatment for two weeks, hypothalamic-pituitary-adrenal axis suppression was observed in one adult and two adolescents at day 14.3 Elevation of potassium levels has been observed in 5% of clascoterone-treated subjects with normal levels vs. 4% of vehicle-treated subjects.3 Clinical experience was limited mainly to white study participants.
Inhibition of lipids and inflammatory cytokines were observed with clascoterone in human sebocytes in vitro.4 The safety and efficacy of clascoterone were evaluated in two international, randomized, double-blind, vehicle-controlled, 12-week trials that included subjects with moderate to severe facial acne vulgaris.3,5 Subjects were mainly white (91%) and female (62%), with 45% age 12-17 years and 55% age 18 years or older. Most had moderate disease (83%), and 17% had severe disease based on Investigator’s Global Assessment (IGA) of acne severity at baseline. IGA is a five-point scale: clear (0), almost clear (1), mild (2), moderate (3), and severe (4). Subjects also presented with a mean inflammatory lesion count of 42.4 and a mean noninflammatory lesion count of 61.4. Subjects were randomized to clascoterone (342 in study 1 and 367 in study 2) or vehicle (350 in study 1 and 362 in study 2). The primary efficacy endpoint was the proportion of subjects with at least a two-point reduction in IGA compared to baseline and an IGA score of 0 or 1, absolute change, and percent change from baseline in acne lesion counts (inflammatory and non-inflammatory) after 12 weeks of treatment.
IGA response rates compared to the vehicle were 18.8% for clascoterone vs. 8.7% for study 1 and 20.9% vs. 6.6%, respectively for study 2. The overall mean reductions in inflammatory lesions were 46% vs. 33% and 31% vs. 19%, respectively, for noninflammatory lesions. Long-term safety was evaluated in an open-label study in which subjects (n = 607) who completed one of the two Phase III trials were administered clascoterone up to nine months.6 Those with an IGA score ≥ 2 continued the drug, and those with an IGA score ≤ 2 were taken off treatment. Subjects were permitted to apply the cream to acne on the trunk as well as the face. The most common adverse events were local erythema and scaling/dryness (9.8% and 4.7% at month 9). No accumulation or increase in adverse events were observed. No corticosteroid-like topical effects (i.e., skin atrophy, telangiectasia, or striae) were observed.
Acne vulgaris is a common cutaneous chronic inflammatory disorder affecting 85% of teenagers.7 Four factors are believed to play vital roles in the pathogenesis, including hyperseborrhea and dysseborrhea, altered keratinization of the pilosebaceous duct, Cutibacterium acnes, and inflammation.2 Androgens play a role in hyperseborrhea and hyperkeratosis as well as alteration in composition of sebum.2 Clascoterone is the first topical androgen receptor inhibitor for moderate acne. The current guideline from the American Academy of Dermatology recommends topical combination of benzoyl peroxide (BP) and antibiotic or retinoid + BP or retinoid + BP + antibiotic.7
Currently, there are no comparative studies of clascoterone to other topical agents. Clascoterone cream provides another option with a different mechanism of action. It is expected to launch in early 2021. Cost information is not yet available.
- Ju Q, Tao T, Hu T, et al. Sex hormones and acne. Clin Dermatol 2017;35:130-137.
- Cong TX, Hao D, Wen X, et al. From pathogenesis of acne vulgaris to anti-acne agents. Arch Dermatol Res 2019;311:337-349.
- Cassiopea, Inc. Winlevi prescribing Information. August 2020.
- Rosette C, Agan FJ, Mazzetti A, et al. Cortexolone 17alpha-propionate (clascoterone) is a novel androgen receptor antagonist that inhibits production of lipids and inflammatory cytokines from sebocytes in vitro. J Drugs Dermatol 2019;18:412-418.
- Hebert A, Thiboutot D, Stein Gold L, et al. Efficacy and safety of topical clascoterone cream, 1%, for treatment in patients with facial acne: Two phase 3 randomized clinical trials. JAMA Dermatol 2020;156:621-630.
- Eichenfield L, Hebert A, Gold LS, et al. Open-label, long-term extension study to evaluate the safety of clascoterone (CB-03-01) cream, 1% twice daily, in patients with acne vulgaris. J Am Acad Dermatol 2020;83:477-485.
- Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol 2016;74:945-973.
Clascoterone should be prescribed to treat acne vulgaris in patients age 12 years and older.
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