The Impact of Clascoterone Topical Cream, 1%: The US Experience 4 Years After Approval and Clinical Expectations for Acne Patients in Other Regions of the World

Acne, a multifactorial disease characterized by hyperkeratinization, Cutibactierumacnes colonization, inflammation, and excess sebum production, primarily affects adolescents and is the eighth most prevalent disease in the world.^1-3 Driven largely by hormonal changes and an increase in androgens and androgen receptor activity during puberty, about 85% of adolescents experience acne with excessive sebum production as a hallmark symptom.^2,4

Clascoterone topical cream, 1% (Winlevi), approved by the US Food and Drug Administration (FDA) in 2020 as the first novel drug introduced for the treatment of acne vulgaris since 1982, is indicated in the US for patients 12 years of age and older.^5-7 The safety and efficacy were supported by two successful Phase 3 randomized controlled trials, one open-label long-term safety study, and five phase 1 and three phase 2 studies.^8-11 Collectively, more than 1,700 acne patients were treated with clascoterone cream prior to FDA approval.⁹

Due to the multifactorial nature of acne pathophysiology, a combination approach to treatment is indicated per the American Academy of Dermatology (AAD) guidelines of care for the management of acne vulgaris.¹² As the first and only topical androgen receptor inhibitor, clascoterone cream filled an unmet need for a non-systemic androgen receptor inhibitor to treat acne in both males and females. Prior to clascoterone’s approval, the only therapies available in the United States to reduce sebum production were oral isotretinoin, oral contraceptives, and off-label use of spironolactone—the last two suitable only for female patients due to adverse systemic effects in males.^13,14 Since its introduction to the United States market in late 2020, clascoterone cream 1% remains the No. 1 prescribed topical for the treatment of acne.¹⁵

CLINICAL EVIDENCE

Real-life clinical experience with clascoterone cream has been captured in case reports and usage patterns from individual physicians.^15-17 Post-marketing experience reveals application site irritation and redness are the most common adverse events, consistent with previous reports.^16,17 The approved US package insert lists potential for hypothalamic-pituitary-adrenal (HPA) axis suppression and hyperkalemia, each based on observations during early phase 2 trials.^5,18 HPA axis suppression was documented based on laboratory changes in maximum use studies in three of 42 subjects. These subjects were using four to six times the recommended amount of clascoterone daily in these studies; evaluations for HPA axis suppression were not required and were not performed in the Phase 3 trials. Hyperkalemia was seen in 5% of subjects treated with clascoterone and 4% of those treated with vehicle in Phase 2 studies. This was also not required or measured in the Phase 3 trials. Of note, post-marketing experience has not shown high frequencies of such occurrences in adolescents or adults using clascoterone cream¹⁹ and laboratory tests to monitor for HPA axis suppression are not required nor recommended.^5,20,21

GLOBAL POTENTIAL

Clascoterone cream is also marketed in Canada and Australia and was recently approved in Singapore. Clascoterone cream is not currently approved in the European Union (EU).

Globally, the prevalence of acne is on the rise, with Western Europe having the highest age standardized prevalent incidence and DALY (Disability-Adjusted Life Years) rates, primarily affecting adolescents.²² Current acne therapeutic recommendations in the EU include topical retinoids as first-line therapy for comedonal acne; fixed-dose combination adapalene and benzoyl peroxide (BPO) or fixed-dose combination BPO and clindamycin for mild-to-moderate papulopustular acne; and systemic antibiotics combined with topical adapalene, with or without BPO, and systemic antibiotics with azelaic acid for severe nodular/conglobate acne. Oral isotretinoin is reserved for severe, recalcitrant acne that has a high risk for psychosocial issues or physical scarring.²³ None of these therapeutic strategies target androgen receptor driven sebum production in both adolescent males and females. Approval of clascoterone cream in the EU would benefit those suffering from acne, particularly adolescents, and fulfill an unmet need in the acne treatment armamentarium.

The US post-marketing experience with clascoterone cream has been positive as indicated by prescribing trends, tolerability, and inclusion in the most recent AAD acne treatment guidelines.¹² As US dermatologists, the collective prescriptions of clascoterone cream to hundreds of adult and adolescent patients has resulted in few observed local skin reactions as the most common adverse event. Among either adults or adolescents, there have not been any untoward systemic side effects like symptoms presumptive of an effect on the HPA axis (eg, Cushing’s syndrome) or symptoms ascribable to systemic antiandrogen effects (eg, perturbation of sexual maturation in young subjects). Furthermore, our dermatology peers have not reported such side effects in presentations at dermatological conferences.

Recent post-marketing studies have shown efficacy and safety in skin of color²⁴ and reduced sebum production25 without compromising facial moisturization, skin barrier function²⁶ or local tolerability. Another study demonstrated clascoterone stability in the presence of other topical treatments including retinoids, antibiotics and/or benzoyl peroxide,²⁷ giving further credence to combination therapy, which is a therapeutic strategy to be considered per the AAD guidelines.¹²

The US clascoterone experience provides a basis for efficacy and safety expectations for diverse populations and the rest of the world. The addition of data from post-marketing studies broadens the understanding of the practical uses of topical clascoterone. Evidence demonstrating clascoterone’s ability to quantitatively reduce sebum production with on-label twice-daily use for 12 weeks²⁵ supports the proposed novel mechanism of action as a topical androgen receptor inhibitor that targets seborrhea by impeding the action of androgens and thus makes it a unique and efficacious therapy for the treatment of acne in males and females. Potential widespread systemic side effects of clascoterone cream have been unfounded in the current US post-marketing experience. Clascoterone’s favorable safety profile has been affirmed, in real-life case publications, and to our knowledge, in clinical experience, yielding no reports of systemic adverse reactions across age subgroups and sex.^16,17,24-27

BEYOND ACNE?

Ongoing efforts to expand the use of clascoterone cream beyond the US warrant support as the value and uniqueness of this therapeutic strategy for the treatment of acne are well established. Furthermore, there is value in exploring clascoterone for other dermatological conditions such as hidradenitis suppurativa, hirsutism, and androgenetic alopecia (AGA). Indeed, two identical international Phase 3 trials are underway examining clascoterone solution for the treatment of male AGA and we look forward to the results.

1. Moradi Tuchayi S, Makrantonaki E, Ganceviciene R, Dessinioti C, Feldman SR, Zouboulis CC. Acne vulgaris. Nat Rev Dis Primers. 2015;1:15029
2. Sutaria AH, Masood S, Saleh HM, et al. Acne Vulgaris. [Updated 2023 Aug 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459173/
3. Tan JK, Bhate K. A global perspective on the epidemiology of acne. Br J Dermatol. 2015;172 Suppl 1:3-12.
4. Lynn DD, Umari T, Dunnick CA, Dellavalle RP. The epidemiology of acne vulgaris in late adolescence. Adolesc Health Med Ther. 2016;7:13-25.
5. Package insert Clascoterone cream, 1% WINLEVI® (Package Insert).Cranbury, NJ: Sun Pharmaceutical Industries; 2020.
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7. Kalabalik-Hoganson J, Frey KM, Ozdener-Poyraz AE, Slugocki M. Clascoterone: a novel topical androgen receptor inhibitor for the treatment of acne. Ann Pharmacother. 2021;55(10):1290-1296.
8. 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(6):621-630.
9. Mazzetti A, Moro L, Gerloni M, Cartwright M. Clinical development of clascoterone (cortexolone 17alpha propionate, CB-03-01) 1% cream for the treatment of acne vulgaris. E-poster presentation. Maui Derm 2019. Maui, Hawaii.
10. Mazzetti A, Moro L, Gerloni M, Cartwright M. Pharmacokinetic profile, safety, and tolerability of clascoterone (cortexolone 17-alpha propionate, CB-03-01) topical cream, 1% in subjects with facial acne vulgaris: an open-label phase 2a study. J Drugs Dermatol. 2019;18(6):563-568.
11. Mazzetti A, Moro L, Gerloni M, Cartwright M. A phase IIb, randomized, double-blind vehicle controlled, dose escalation study evaluating clascoterone 0.1%, 0.5%, and 1% topical cream in subjects with facial acne. J Drugs Dermatol. 2019;18(6):570-575.
12. Reynolds RV, Yeung H, Cheng CE, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2024;90(5):1006.e1-1006.e30.
13. Elsaie ML. Hormonal treatment of acne vulgaris: an update. Clin Cosmet Investig Dermatol. 2016;9:241-248.
14. Layton AM, Eady EA, Whitehouse H, Del Rosso JQ, Fedorowicz Z, van Zuuren EJ. Oral spironolactone for acne vulgaris in adult females: a hybrid systematic review. Am J Clin Dermatol. 2017;18:169-191.
15. Data on file. Cosmo Pharmacueticals. 2025.
16. Lynde C, Abdulla S, Andriessen A, et al.Real-world cases of clascoterone topical treatment for acne and related disorders. J Drugs Dermatol. 2025;24(1):73361s3-73361s14.
17. Tay E, Loo WJ. Real-world experience of clascoterone cream 1% in acne management: case series and canadian experience. Clin Cosmet Investig Dermatol. 2025;18:161-167. Published 2025 Jan 20.
18. Center For Drug Evaluation and Research. Application. Number: 213433orig1s000 Risk Assessment and Risk Mitigation Review(s). August 2020. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213433Orig1s000RiskR.pdf
19. Libecco J, Eichenfield L, Hebert A, Stein Gold L, Cartwright, M, Moro L, Lionnet, L, Squittieri N, Kyeremateng K, Shukla D, Mazzetti A. Phase 3 efficacy of clascoterone cream 1% in patients with acne vulgaris: a post hoc subgroup analysis by sex. American Academy of Dermatology (AAD) Annual Meeting, 2024. San Diego, CA,
20. Del Rosso J, Stein Gold L, Squittieri N, Thiboutot D. Is there a clinically relevant risk of hyperkalemia with topical clascoterone treatment? J Clin Aesthet Dermatol. 2023 Jun;16(6):20-24. PMID: 37361363; PMCID: PMC10286882.
21. Bhatia N, Eichenfield LF, Mazzetti A, Moro L, Squittieri N, Hebert AA. Hypothalamic-Pituitary-Adrenal axis response in patients with acne vulgaris treated with clascoterone. J Drugs Dermatol. 2024;23(6):433-437. doi:10.36849/JDD.7997
22. Zhu Z, Zhong X, Luo Z, et al. Global, regional and national burdens of acne vulgaris in adolescents and young adults aged 10-24 years from 1990 to 2021: a trend analysis. Br J Dermatol. 2025;192(2):228-237. doi:10.1093/bjd/ljae352
23. Nast A, Dréno B, Bettoli V, et al. European evidence-based (S3) guideline for the treatment of acne - update 2016 - short version. J Eur Acad Dermatol Venereol. 2016;30(8):1261-1268. doi:10.1111/jdv.13776
24. Kircik L, Draelos ZD, Kyeremateng K, Squttieri N, Taylor SC. Efficacy and safety of clascoterone cream 1% in patients with acne with skin of color: 16-week interim analysis. Poster presentation. Winter Clinical-Miami 2025. Miami, FL.
25. Draelos ZD, Kyeremateng K, Squttieri N. Reduction in facial sebum production following treatment with clascoterone cream 1% in patients with acne vulgaris: 12-week interim analysis. Poster presentation. Fall Clinical Dermatology 2024. Las Vegas, NV.
26. Draelos ZD, Kyeremateng K, Squttieri M. Improvement in skin moisturization and lack of skin barrier damage following treatment with clascoterone cream 1%:a randomized, single blind split face study in acne-prone individuals. Poster presentation. SCALE 2024, Nashville, TN.
27. Draelos ZD, Kyeremateng K, Squttieri M. Clascoterone stability when combined with topical acne medications. Poster presentation. Winter Clinical-Miami 2025. Miami, FL.

Disclosures: Both authors have received fees from Cassiopea SpA, Cosmo, and/or Sun Pharmaceuticals Inc related to clascoterone. 

Adelaide Hebert, MD

• Professor of Dermatology and Pediatrics, The University of Texas Medical School Houston, Houston, TX.

Leon Kircik, MD

• Clinical Professor of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
• Adjunct Clinical Professor of Dermatology, Indiana University School of Medicine, Indianapolis, IN.