Acne vulgaris is a chronic inflammatory disease of the face and trunk and one of the most prevalent skin diseases, affecting approximately 10% of the global population overall, but a much higher percentage of adolescents and young adults.
While we have many existing antiacne treatments available, most of these treatments have potential side effects and some patients are poorly compliant, therefore new treatments that become available for dermatologist and clinician prescribing are enthusiastically welcomed.
The first in a novel category of treatments is a new topical androgen receptor inhibitor called cortoxolone- 17-alpha proprionate, or Clascoterone cream. It has recently been approved in the US and will hopefully soon be available as a prescription cream in UK.
Clascoterone acts as an androgen receptor blocker. It works by inhibiting testosterone and dihydrotestosterone (DHT) when applied to skin. It is applied over the whole acne prone skin area on the face, back or chest and is also being developed to treat androgenetic alopecia.1 Because it is a topical, interactions with other drugs are unlikely and side effects are minimal.
Androgens are regulators of sebum production and play a key role in the pathogenesis of acne. They then contribute to inflammatory lesions and can potentially cause more severe acne and scarring.
Androgen receptor inhibition has been available with systemic agents for some time – as with some oral contraceptive pills as well as spironolactone – and is well established for the management of appropriate clinical patterns of acne in women. However, there are potential side effects from these systemic treatments, including with the oral contraceptive pill, such as deep-vein thrombosis, melasma and other side effects.
Meanwhile, while spironolactone has proved to be highly effective in the long-term management of acne for some women, it clearly cannot be used in males, and can also can occasionally cause breast tenderness and swelling in some women.
For these reasons – not to mention some patients simply dislike taking systemic treatment and pregnancy avoidance is essential – the availability of a topical androgen receptor inhibitor is a welcome addition to our treatment armamentarium.
The efficacy of Clascoterone cream has been well established in several international multi-centre placebocontrolled studies with large patient numbers.2-6 The safety profile was acceptable and interestingly, not significantly different from the vehicle, showing a small number of cases of skin irritancy.
When Clascoterone becomes available in the UK I will prescribe it for male and female patients as either single therapy for those with milder, non-inflammatory acne, comedogenic acne and seborrhoea, or in combination with an anti-acne topical retinoid such as Differin cream or gel. For more inflammatory and severe acne I will combine Clascoterone cream with existing treatments including oral antibiotics, alternating with other topical anti-acne treatments such as adapalene, benzoyl peroxide and azalaic acid. For very severe acne I will prescribe Clascoterone cream in combination with oral isotretinoin.
With further experience it may be possible to use this new cream to reduce the dosages and duration of systemic treatment. The goal for acne treatment is prompt disease control which then reduces the risk of psychological and cutaneous scarring. Therefore, any new treatment to help us reach this goal is welcome.
1. Sun HY, Sebaratnam DF. Clascoterone as a novel treatment for androgenetic alopecia. Clin Exp Dermatol. 2020 Oct;45(7):913-914. doi: 10.1111/ced.14292. Epub 2020 Jun 23. PMID: 32421862.
2. Eichenfield L, Hebert A, Gold LS, Cartwright M, Fragasso E, Moro L, Mazzetti A. 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 Aug;83(2):477-485. doi: 10.1016/j.jaad.2020.04.087. Epub 2020 Apr 26. PMID: 32348828.
3. 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 Jun 1;18(6):563. PMID: 31251549.
4. Rosette C, Agan FJ, Mazzetti A, Moro L, Gerloni M. Cortexolone 17α-propionate (Clascoterone) Is a Novel Androgen Receptor Antagonist that Inhibits Production of Lipids and Inflammatory Cytokines from Sebocytes In Vitro. J Drugs Dermatol. 2019 May 1;18(5):412-418. PMID: 31141847.
5. Hebert A, Thiboutot D, Stein Gold L, Cartwright M, Gerloni M, Fragasso E, Mazzetti A. Efficacy and Safety of Topical Clascoterone Cream, 1%, for Treatment in Patients With Facial Acne: Two Phase 3 Randomized Clinical Trials. JAMA Dermatol. 2020 Jun 1;156(6):621-630. doi: 10.1001/ jamadermatol.2020.0465. PMID: 32320027; PMCID: PMC7177662.
6. Dhillon S. Clascoterone: First Approval. Drugs. 2020 Nov;80(16):1745-1750. doi: 10.1007/s40265-020-01417-6. PMID: 33030710.
DR NICK LOWE
Dr Nick Lowe is a consultant dermatologist at Cranley Clinic, London and clinical professor of Dermatology at UCLA School of Medicine, Los Angeles. He is a Fellow of the Royal College of Physicians, American Academy of Dermatology and American Society of Laser Medicine and Surgery. He has authored more than 450 clinical and research publications, 15 scientific and five educational books.