clascoterone

Clascoterone is indicated for the topical treatment of acne vulgaris in people aged twelve years of age and older.{{cite journal | vauthors = Barbieri JS | title = A New Class of Topical Acne Treatment Addressing the Hormonal Pathogenesis of Acne | journal = JAMA Dermatology | volume = 156 | issue = 6 | pages = 619–620 | date = Jun 2020 | pmid = 32320045 | doi = 10.1001/jamadermatol.2020.0464 | issn = 2168-6068 | s2cid = 216075268 }}

Two large phase III randomized controlled trials evaluated the effectiveness of clascoterone for the treatment of acne over a period of 12 weeks.{{cite journal | vauthors = Hebert A, Thiboutot D, Stein Gold L, Cartwright M, Gerloni M, Fragasso E, Mazzetti A | title = Efficacy and Safety of Topical Clascoterone Cream, 1%, for Treatment in Patients With Facial Acne: Two Phase 3 Randomized Clinical Trials | journal = JAMA Dermatology | volume = 156 | issue = 6 | pages = 621–630 | date = April 2020 | pmid = 32320027 | pmc = 7177662 | doi = 10.1001/jamadermatol.2020.0465 }} Clascoterone decreased acne symptoms by about 8 to 18% more than placebo. The defined treatment success endpoint was achieved in about 18 to 20% of individuals with clascoterone relative to about 7 to 9% of individuals with placebo. The comparative effectiveness of clascoterone between males and females was not described.

A small pilot randomized controlled trial in 2011 found that clascoterone cream decreased acne symptoms to a similar or significantly greater extent than tretinoin 0.05% cream.{{cite journal | vauthors = Trifu V, Tiplica GS, Naumescu E, Zalupca L, Moro L, Celasco G | title = Cortexolone 17α-propionate 1% cream, a new potent antiandrogen for topical treatment of acne vulgaris. A pilot randomized, double-blind comparative study vs. placebo and tretinoin 0·05% cream | journal = The British Journal of Dermatology | volume = 165 | issue = 1 | pages = 177–183 | date = Jul 2011 | pmid = 21428978 | doi = 10.1111/j.1365-2133.2011.10332.x | s2cid = 38404925 }} No active comparator was used in the phase III clinical trials of clascoterone for acne. Hence, it's unclear how clascoterone compares to other therapies used in the treatment of acne.

Clascoterone is available in the form of a 1% (10 mg/g) cream for topical use.

The effects of local skin reactions with clascoterone were similar to placebo in two large phase III randomized controlled trials. Suppression of the hypothalamic–pituitary–adrenal axis (HPA axis) may occur during clascoterone therapy in some individuals due to its cortexolone metabolite. HPA axis suppression as measured by the cosyntropin stimulation test was observed to occur in 3 of 42 (7%) of adolescents and adults using clascoterone for acne. HPA axis function returned to normal within 4 weeks following discontinuation of clascoterone. Hyperkalemia (elevated potassium levels) occurred in 5% of clascoterone-treated individuals and 4% of placebo-treated individuals.

Clascoterone is a steroidal antiandrogen, or antagonist of the androgen receptor (AR), the biological target of androgens such as testosterone and dihydrotestosterone (DHT).{{cite journal | vauthors = Rosette C, Rosette N, Mazzetti A, Moro L, Gerloni M | title = Cortexolone 17α-Propionate (Clascoterone) is an Androgen Receptor Antagonist in Dermal Papilla Cells In Vitro | journal = Journal of Drugs in Dermatology | volume = 18 | issue = 2 | pages = 197–201 | date = February 2019 | pmid = 30811143 }}{{cite journal | vauthors = Rosette C, Agan FJ, Mazzetti A, Moro L, Gerloni M | title = Cortexolone 17α-propionate (Clascoterone) Is a Novel Androgen Receptor Antagonist that Inhibits Production of Lipids and Inflammatory Cytokines from Sebocytes In Vitro | journal = Journal of Drugs in Dermatology | volume = 18 | issue = 5 | pages = 412–418 | date = May 2019 | pmid = 31141847 }} In a bioassay, the topical potency of the medication was greater than that of progesterone, flutamide, and finasteride and was equivalent to that of cyproterone acetate.{{cite journal | vauthors = Celasco G, Moro L, Bozzella R, Ferraboschi P, Bartorelli L, Quattrocchi C, Nicoletti F | title = Biological profile of cortexolone 17alpha-propionate (CB-03-01), a new topical and peripherally selective androgen antagonist | journal = Arzneimittel-Forschung | volume = 54 | issue = 12 | pages = 881–886 | year = 2004 | pmid = 15646372 | doi = 10.1055/s-0031-1297043 | s2cid = 36709725 }} Likewise, it is significantly more efficacious as an antiandrogen than other AR antagonists such as enzalutamide and spironolactone in scalp dermal papilla cells and sebocytes in vitro.

Steady-state levels of clascoterone occur within 5 days of twice daily administration. At a dosage of 6 g clascoterone cream applied twice daily, maximal circulating levels of clascoterone were 4.5 ± 2.9 ng/mL, area-under-the-curve levels over the dosing interval were 37.1 ± 22.3 h*ng/mL, and average circulating levels of clascoterone were 3.1 ± 1.9 ng/mL. In rodents, clascoterone has been found to possess strong local antiandrogenic activity, but negligible systemic antiandrogenic activity when administered via subcutaneous injection. Along these lines, the medication is not progonadotropic in animals.

The plasma protein binding of clascoterone is 84 to 89% regardless of concentration.

Clascoterone is rapidly hydrolyzed into cortexolone (11-deoxycortisol) and this compound is a possible primary metabolite of clascoterone based on in-vitro studies in human liver cells. During treatment with clascoterone, cortexolone levels were detectable and generally below or near the low limit of quantification (0.5 ng/mL). Clascoterone may also produce other metabolites, including conjugates.

The elimination of clascoterone has not been fully characterized in humans.

{{See also|List of steroidal antiandrogens#Cortisol derivatives}}

Clascoterone, also known as cortexolone 17α-propionate or 11-deoxycortisol 17α-propionate, as well as 17α,21-dihydroxyprogesterone 17α-propionate or 17α,21-dihydroxypregn-4-en-3,20-dione 17α-propionate, is a synthetic pregnane steroid and a derivative of progesterone and 11-deoxycortisol (cortexolone).{{Cite web | title = ChemIDplus - 19608-29-8 - GPNHMOZDMYNCPO-PDUMRIMRSA-N - Clascoterone [USAN] - Similar structures search, synonyms, formulas, resource links, and other chemical information | url = https://chem.nlm.nih.gov/chemidplus/rn/19608-29-8 }} It is specifically the C17α propionate ester of 11-deoxycortisol.

An analogue of clascoterone is 9,11-dehydrocortexolone 17α-butyrate (CB-03-04).{{cite journal | vauthors = Celasco G, Moroa L, Bozzella R, Ferraboschi P, Bartorelli L, Di Marco R, Quattrocchi C, Nicoletti F | title = Pharmacological profile of 9,11-dehydrocortexolone 17alpha-butyrate (CB-03-04), a new androgen antagonist with antigonadotropic activity | journal = Arzneimittel-Forschung | volume = 55 | issue = 10 | pages = 581–587 | date = 2005 | pmid = 16294504 | doi = 10.1055/s-0031-1296908 | s2cid = 35386850 }}Corticosteroids related to clascoterone, for instance cortisone acetate and prednisolone acetate, show antiandrogenic activity in animals similarly to clascoterone.{{cite journal | vauthors = Lerner LJ | title = Androgen antagonists | journal = Pharmacology & Therapeutics. Part B: General & Systematic Pharmacology | volume = 1 | issue = 2 | pages = 217–231 | date = 1975 | pmid = 772705 | doi = 10.1016/0306-039x(75)90006-9 }}

C17α esters of 11-deoxycortisol were unexpectedly found to possess antiandrogenic activity. Clascoterone, also known as cortexolone 17α-propionate, was selected for development based on its optimal drug profile. The medication was approved by the US Food and Drug Administration (FDA) for the treatment of acne in August 2020.

The FDA approved clascoterone based on evidence from two clinical trials (Trial 1/NCT02608450 and Trial 2/NCT02608476) of 1,440 participants 9 to 58 years of age with acne vulgaris. The trials were conducted at 99 sites in the United States, Poland, Romania, Bulgaria, Ukraine, Georgia, and Serbia.{{cite web | title = Drug Trial Snapshot: Winlevi | date = 26 August 2020 | website = U.S. Food and Drug Administration (FDA) | url = https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trial-snapshot-winlevi | archive-url = https://web.archive.org/web/20201029051157/https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trial-snapshot-winlevi | url-status = dead | archive-date = 29 October 2020 | access-date = 10 September 2020 }} {{PD-notice}} Participants applied clascoterone or vehicle (placebo) cream twice daily for 12 weeks. Neither the participants nor the health care providers knew which treatment was being given until after the trial was completed. The benefit of clascoterone in comparison to placebo was assessed after 12 weeks of treatment using the Investigator's Global Assessment (IGA) score that measures the severity of disease (on a scale from 0 to 4) and a decrease in the number of acne lesions.

In April 2025, the European Medicines Agency (EMA) recommended the refusal of a marketing authorization for Winlevi, a medicine intended for treating acne vulgaris.{{cite web | title = Winlevi EPAR | date = 30 April 2025 | website = European Medicines Agency (EMA) | url = https://www.ema.europa.eu/en/medicines/human/EPAR/winlevi | access-date = 2 May 2025 }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. The EMA noted that Winlevi is a new class of medicine that blocks receptors for androgens. However, there is a risk of the medicine suppressing the working of three organs: the hypothalamus and pituitary glands in the brain and adrenal glands. The suppression of these organs could lead to impaired growth and sexual maturation, which is a major concern in adolescents. Although the company presented data to show that the risk was low, the EMA considered that these data, as well as measures the company proposed to minimize the risk, were not sufficient to approve the medicine for people from 12 years of age to less than 18 years of age.

Clascoterone is the international nonproprietary name and the United States Adopted Name.{{cite journal | vauthors = ((World Health Organization)) | title = International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 82 | journal = WHO Drug Information | volume = 33 | issue = 3 | pages = 106 | year = 2019 | hdl = 10665/330879 | hdl-access = free }}

Clascoterone has been suggested as a possible treatment for hidradenitis suppurativa (acne inversa), an androgen-dependent skin condition.{{cite journal | vauthors = Der Sarkissian SA, Sun HY, Sebaratnam DF | title = Cortexolone 17 α-proprionate for hidradenitis suppurativa | journal = Dermatologic Therapy | volume = 33 | issue = 6 | pages = e14142 | date = August 2020 | pmid = 32761708 | doi = 10.1111/dth.14142 | s2cid = 221036602 | doi-access = free }}

{{Reflist}}

• {{ClinicalTrialsGov|NCT02608450|A Study to Evaluate the Safety and Efficacy of CB-03-01 Cream, 1% in Subjects With Facial Acne Vulgaris (25)}}
• {{ClinicalTrialsGov|NCT02608476|A Study to Evaluate the Safety and Efficacy of CB-03-01 Cream, 1% in Subjects With Facial Acne Vulgaris (26)}}

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