Clascoterone for acne

Approved indication: topical treatment of acne vulgaris in patients 12 years of age and older
Winlevi (Sun Pharma)
cream containing 10 mg/g

Acne vulgaris, or acne, is a common skin condition, affecting approximately 9.4% of people worldwide and can significantly impact quality of life.¹ While it is more common in adolescents, it can persist into adulthood. Acne is usually caused by increased sensitivity of the pilosebaceous unit (consisting of a hair follicle and its associated sebaceous gland) to circulating androgens.² It is characterised by increased sebum production, hyperkeratinisation of hair follicles, bacterial growth and inflammation. Topical treatments are used for milder forms of acne, such as benzoyl peroxide, retinoids and antibiotics, while moderate to severe acne may require oral antibiotics, isotretinoin or antiandrogens (e.g. the combined oral contraceptive pill, spironolactone).³

Clascoterone is a topical androgen receptor antagonist and competes with dihydrotestosterone for androgen receptors in the pilosebaceous unit. This results in reduced sebum production and inflammation.⁴ The drug acts locally with minimal systemic absorption.^5,6

The efficacy and safety of clascoterone for moderate to severe facial acne were evaluated in 2 similar randomised, double-blind, vehicle-controlled phase 3 trials involving a total of 1421 participants (mean age 19 years). Moderate to severe acne was defined as grade 3 or 4 on the Investigator’s Global Assessment (IGA) scale of acne severity. The trials excluded those with more than 2 facial nodules, nodulocystic acne, or who were using other anti-acne medications. Participants were randomised to receive treatment with clascoterone cream or vehicle cream (inactive product), applied to the whole face twice daily for 12 weeks.⁴ Treatment success was defined as at least a 2-point reduction in IGA score from baseline and an IGA score of zero (clear) or one (almost clear). Other efficacy measures were the absolute change from baseline in noninflammatory lesion count and inflammatory lesion count. All outcomes were assessed after 12 weeks of treatment.⁴

According to pooled trial data, more participants achieved treatment success when treated with clascoterone compared with the vehicle (19.9% versus 7.7%, p<0.0001). In patients treated with clascoterone, there was a greater absolute change from baseline in noninflammatory lesion count (−20.8 versus −11.9, p<0.0001) and inflammatory lesion count (−19.7 versus −14.0, p<0.0001), compared with patients treated with the vehicle.⁴ Efficacy was increased in participants that continued in the open-label, 9-month extension study.⁷

Most adverse effects associated with clascoterone cream were mild or moderately severe, with similar incidences between the clascoterone and vehicle groups. Common adverse effects included local skin reactions, nasopharyngitis, headache and oropharyngeal pain.^4,8 Local skin reactions were mostly minimal or mild in severity, the most frequent being erythema, scaling or dryness, and skin atrophy. Other local skin reactions included pruritus, striae rubrae (stretch marks), oedema, telangiectasia (appearance of blood vessels on the skin) and stinging or burning.

Clascoterone is metabolised to cortexolone which has weak glucocorticoid effects. The use of clascoterone was associated with reversible hypothalamic–pituitary–adrenal (HPA) axis suppression in clinical studies where people were exposed to 3 times the recommended daily dose. All patients returned to normal HPA axis function at follow-up 4 weeks after stopping treatment.^6,8 Caution should be exercised when using clascoterone in settings that may increase systemic absorption (e.g. use of occlusive dressings, prolonged use, application over large surface areas).⁸

Clascoterone should not be used in pregnancy (Therapeutic Goods Administration category D) because of teratogenicity and embryofetal death, which were observed in animal studies. There are no available data on its use in breastfeeding.⁸

After cleansing and drying the skin, clascoterone cream should be applied as a thin layer twice a day (morning and evening) to the entire acne-prone area. It should not be applied to cuts, abrasions, sunburn or eczema-affected skin. Hands should be washed before and after application. The product should be stored in a refrigerator prior to dispensing and discarded 6 months after the date it was dispensed.⁸

As with other acne treatments, patients should limit their use of potentially irritating topical products (e.g. medicated soaps or cleansers, products with high alcohol concentration) as these may increase the likelihood of local skin irritation.⁸

Clascoterone cream appears to be a well-tolerated and effective treatment for people aged 12 years and older with moderate to severe acne, with a different mechanism of action from existing topical treatments. Head-to-head comparisons between clascoterone and first-line topical agents are lacking, and further data are needed to inform its place in therapy.

This new drug comment was finalised on 20 August 2024.

🅃 🅃 manufacturer provided additional useful information. The Transparency Score is explained in New drugs: transparency, Vol 37 No 1, Aust Prescr 2014;37:27.

At the time the comment was prepared, information about this drug was available on the websites of the Food and Drug Administration in the USA, the European Medicines Agency and the Therapeutic Goods Administration.

 

References

1. Tan JK, Bhate K. A global perspective on the epidemiology of acne. Br J Dermatol 2015;172 Suppl 1:3-12.
2. Acne. In: Therapeutic Guidelines. Melbourne: Therapeutic Guidelines Limited; 2022. [cited 2024 Aug 12]
3. Williams HC, Dellavalle RP, Garner S. Acne vulgaris. Lancet 2012;379:361-72.
4. Hebert A, Eichenfield L, Thiboutot D, Stein Gold L, Vassileva S, Mihaylova Y, et al. Efficacy and Safety of 1% Clascoterone Cream in Patients Aged > 12 Years With Acne Vulgaris. J Drugs Dermatol 2023;22:174-81.
5. 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 Acne Vulgaris: An Open-Label Phase 2a Study. J Drugs Dermatol 2019;18:563.
6. Therapeutic Goods Administration. Australian Public Assessment Report for Winlevi. Department of Health and Aged Care; 2024. [cited 2024 Aug 19]
7. Eichenfield LF, Hebert AA, Gold LS, Cartwright M, Moro L, Han J, et al. Long-Term Safety and Efficacy of Twice-Daily Topical Clascoterone Cream 1% in Patients Greater Than or Equal to 12 Years of Age With Acne Vulgaris. J Drugs Dermatol 2023;22:810-6.
8. Therapeutic Goods Administration. Australian Product Information – Winlevi (clascoterone) cream. Department of Health and Aged Care; 2024. [cited 2024 May 28]

 The new drug commentaries in Australian Prescriber are prepared by the editors and reviewed by the Editorial Advisory Committee. Some of the views expressed on newly approved products should be regarded as preliminary, as there may be limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Advisory Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.