Clascoterone

{{Short description|Chemical compound}} {{Use dmy dates|date=October 2023}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | image = Cortexolone 17α-propionate.svg | image_class = skin-invert-image | width = 250 | alt = | caption =

| pronounce = | tradename = Winlevi | Drugs.com = {{drugs.com|monograph|clascoterone-topical}} | MedlinePlus = | DailyMedID = Clascoterone | pregnancy_AU = D | pregnancy_AU_comment = <ref name="Winlevi APMDS" /> | pregnancy_category= | routes_of_administration = Topical | class = | ATC_prefix = D10 | ATC_suffix = AX06 | ATC_supplemental =

| legal_AU = S4 | legal_AU_comment = <ref name="Winlevi APMDS">{{cite web | title = Winlevi APMDS | date = 17 May 2024 | website = Therapeutic Goods Administration (TGA) | url = https://www.tga.gov.au/resources/auspmd/winlevi | access-date = 10 June 2024 }}</ref> | legal_BR =  | legal_BR_comment = | legal_CA = Rx-only | legal_CA_comment = <ref>{{cite web | title = Details for: Winlevi | date = 8 September 2023 | website = Health Canada | url = https://dhpp.hpfb-dgpsa.ca/dhpp/resource/102757 | access-date = 3 March 2024 }}</ref><ref>{{cite web | title = Summary Basis of Decision for Winlevi | date = 30 August 2023 | website = Health Canada | url = https://dhpp.hpfb-dgpsa.ca/review-documents/resource/SBD1693490140440 | access-date = 4 October 2023 }}</ref><ref>{{cite web | title = Details for: Winlevi | date = 8 September 2023 | website = Health Canada | url = https://dhpp.hpfb-dgpsa.ca/dhpp/resource/102757 | access-date = 4 October 2023 }}</ref> | legal_DE =  | legal_DE_comment = | legal_NZ =  | legal_NZ_comment = | legal_UK =  | legal_UK_comment = | legal_US = Rx-only | legal_US_comment = <ref name="Winlevi FDA label" /> | legal_EU = | legal_EU_comment = | legal_UN =  | legal_UN_comment = | legal_status =

| IUPAC_name = [(8''R'',9''S'',10''R'',13''S'',14''S'',17''R'')-17-(2-hydroxyacetyl)-10,13-dimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1''H''-cyclopenta[''a'']phenanthren-17-yl] propanoate | C=24 | H=34 | O=5 | SMILES = CCC(=O)O[C@@]1(CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CCC4=CC(=O)CC[C@]34C)C)C(=O)CO | StdInChI = 1S/C24H34O5/c1-4-21(28)29-24(20(27)14-25)12-9-19-17-6-5-15-13-16(26)7-10-22(15,2)18(17)8-11-23(19,24)3/h13,17-19,25H,4-12,14H2,1-3H3/t17-,18+,19+,22+,23+,24+/m1/s1 | StdInChI_comment = | StdInChIKey = GPNHMOZDMYNCPO-PDUMRIMRSA-N | density = | density_notes = | melting_point = | melting_high = | melting_notes = | boiling_point = | boiling_notes = | solubility = | sol_units = | specific_rotation = }}

'''Clascoterone''', sold under the brand name '''Winlevi''', is an antiandrogen medication which is used topically in the treatment of acne.<ref name="Winlevi FDA label">{{cite web | title=Winlevi- clascoterone cream | website=DailyMed | date=2 January 2025 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1673a84b-7f5c-47ab-a99c-1e3db21a6a09 | access-date=15 June 2025}}</ref> The medication is used as a cream by application to the skin, for instance the face and scalp.<ref name="Kircik_2019" /> Clascoterone is an antiandrogen, or antagonist of the androgen receptor (AR), the biological target of androgens such as testosterone and dihydrotestosterone.<ref name="Rosette_2019" /><ref name="Rosette_2019a" /> It shows minimal systemic absorption when applied to skin.<ref name="Kircik_2019" />

Clascoterone was developed by Cassiopea and was approved for medical use in the United States in August 2020 and in the European Union in October 2025.<ref>{{cite web | title=Drug Approval Package: Winlevi | website=U.S. Food and Drug Administration (FDA) | date=29 September 2020 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213433Orig1s000TOC.cfm | access-date=15 June 2025}}</ref><ref name="Cassiopea2020">{{cite press release | title=Cassiopea Receives FDA Approval for Winlevi (clascoterone cream 1%), First-in-Class Topical Acne Treatment Targeting the Androgen Receptor | publisher=Cassiopea | via=PR Newswire | date=27 August 2020 | url=https://www.prnewswire.com/news-releases/cassiopea-receives-fda-approval-for-winlevi-clascoterone-cream-1-first-in-class-topical-acne-treatment-targeting-the-androgen-receptor-301119454.html | access-date=15 June 2025}}</ref><ref>{{cite web | title=Winlevi Authorisation Details | website=European Medicines Agency | date=17 October 2025 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/winlevi#authorisation-details | access-date=25 March 2026}}</ref> The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.<ref>{{cite web | title = New Drug Therapy Approvals 2020 | date = 31 December 2020 | website = U.S. Food and Drug Administration (FDA) | url = https://fda.report/media/144982/final+FINAL+NewDrugsApprovalReport_Final2020_210108_0948_FINAL.pdf | access-date = 17 January 2021 }} {{PD-notice}}</ref>

==Medical uses== Clascoterone is indicated for the topical treatment of acne vulgaris in people aged twelve years of age and older.<ref name="Winlevi FDA label" /><ref name="Barbieri_2020">{{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 }}</ref>

Two large phase III randomized controlled trials evaluated the effectiveness of clascoterone for the treatment of acne over a period of 12 weeks.<ref name="Winlevi FDA label" /><ref name="Barbieri_2020" /><ref name="Hebert_2020">{{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 }}</ref> Clascoterone decreased acne symptoms by about 8 to 18% more than placebo.<ref name="Winlevi FDA label" /><ref name="Hebert_2020" /> 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.<ref name="Winlevi FDA label" /><ref name="Barbieri_2020" /><ref name="Hebert_2020" /> The comparative effectiveness of clascoterone between males and females was not described.<ref name="Winlevi FDA label" /><ref name="Hebert_2020" />

==Side effects== The effects of local skin reactions with clascoterone were similar to placebo in two large phase III randomized controlled trials.<ref name="Winlevi FDA label" /><ref name="Hebert_2020" /> Suppression of the hypothalamic–pituitary–adrenal axis (HPA axis) may occur during clascoterone therapy in some individuals due to its cortexolone metabolite.<ref name="Winlevi FDA label" /><ref name="Barbieri_2020" /> 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.<ref name="Winlevi FDA label" /><ref name="Barbieri_2020" /> HPA axis function returned to normal within 4 weeks following discontinuation of clascoterone.<ref name="Winlevi FDA label" /><ref name="Barbieri_2020" /> Hyperkalemia (elevated potassium levels) occurred in 5% of clascoterone-treated individuals and 4% of placebo-treated individuals.<ref name="Winlevi FDA label" />

==Pharmacology==

===Pharmacodynamics=== Clascoterone is a steroidal antiandrogen, or antagonist of the androgen receptor (AR), the biological target of androgens such as testosterone and dihydrotestosterone (DHT).<ref name="Winlevi FDA label" /><ref name="Rosette_2019">{{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 }}</ref><ref name="Rosette_2019a">{{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 }}</ref> 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.<ref name="Celasco_2004">{{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 }}</ref> 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''.<ref name="Rosette_2019a" />

===Pharmacokinetics=== Steady-state levels of clascoterone occur within 5 days of twice daily administration.<ref name="Winlevi FDA label" /> 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.<ref name="Winlevi FDA label" /> In rodents, clascoterone has been found to possess strong local antiandrogenic activity, but negligible systemic antiandrogenic activity when administered via subcutaneous injection.<ref name="Celasco_2004" /> Along these lines, the medication is not progonadotropic in animals.<ref name="Celasco_2004" />

The plasma protein binding of clascoterone is 84 to 89% regardless of concentration.<ref name="Winlevi FDA label" />

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.<ref name="Winlevi FDA label" /><ref name="Barbieri_2020" /> During treatment with clascoterone, cortexolone levels were detectable and generally below or near the low limit of quantification (0.5 ng/mL).<ref name="Winlevi FDA label" /> Clascoterone may also produce other metabolites, including conjugates.<ref name="Winlevi FDA label" />

The elimination of clascoterone has not been fully characterized in humans.<ref name="Winlevi FDA label" />

==Chemistry== {{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).<ref name="ChemIDplus">{{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://pubchem.ncbi.nlm.nih.gov/#tab/sidsrcname=ChemIDplus&query=19608-29-8&input_type=text }}</ref> It is specifically the C17α propionate ester of 11-deoxycortisol.<ref name="Celasco_2004" />

An analogue of clascoterone is 9,11-dehydrocortexolone 17α-butyrate (CB-03-04).<ref name="Celasco_2005">{{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 }}</ref>Corticosteroids related to clascoterone, for instance cortisone acetate and prednisolone acetate, show antiandrogenic activity in animals similarly to clascoterone.<ref name="Lerner_1975">{{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 }}</ref>

==History== C17α esters of 11-deoxycortisol were unexpectedly found to possess antiandrogenic activity.<ref name="Celasco_2004" /> Clascoterone, also known as cortexolone 17α-propionate, was selected for development based on its optimal drug profile.<ref name="Celasco_2004" /> The medication was approved by the US Food and Drug Administration (FDA) for the treatment of acne in August 2020.<ref name="Cassiopea2020" />

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.<ref name="FDA snapshot" /> The trials were conducted at 99 sites in the United States, Poland, Romania, Bulgaria, Ukraine, Georgia, and Serbia.<ref name="FDA snapshot">{{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 | archive-date = 29 October 2020 | access-date = 10 September 2020 }} {{PD-notice}}</ref> Participants applied clascoterone or vehicle (placebo) cream twice daily for 12 weeks.<ref name="FDA snapshot" /> Neither the participants nor the health care providers knew which treatment was being given until after the trial was completed.<ref name="FDA snapshot" /> 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.<ref name="FDA snapshot" />

==Society and culture== === Legal status === In April 2025, the European Medicines Agency (EMA) recommended the refusal of a marketing authorization for Winlevi, a medicine intended for treating acne vulgaris.<ref name="Winlevi EPAR">{{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.</ref> The EMA noted that Winlevi is a new class of medicine that blocks receptors for androgens.<ref name="Winlevi EPAR" /> 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.<ref name="Winlevi EPAR" /> The suppression of these organs could lead to impaired growth and sexual maturation, which is a major concern in adolescents.<ref name="Winlevi EPAR" /> 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.<ref name="Winlevi EPAR" /> In May 2025, Cassiopea requested a re-examination of the EMA's April 2025 opinion.<ref name="Winlevi EPAR" /> In October 2025, EMA issued marketing authorization for Winlevi.<ref>{{cite web | title=Winlevi Authorisation Details | website=European Medicines Agency | date=17 October 2025 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/winlevi#authorisation-details | access-date=25 March 2026}}</ref>

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

==Research== ===Scalp hair loss=== Clascoterone is under development for the treatment of androgen-dependent scalp hair loss.<ref name="AdisInsight">{{Cite web | title = Clascoterone - Cassiopea - AdisInsight | url = http://adisinsight.springer.com/drugs/800026561 }}</ref><ref name="Kircik_2019">{{cite journal | vauthors = Kircik LH | title = What's new in the management of acne vulgaris | journal = Cutis | volume = 104 | issue = 1 | pages = 48–52 | date = July 2019 | pmid = 31487336 | url = https://www.mdedge.com/dermatology/article/204308/acne/whats-new-management-acne-vulgaris }}</ref> Two phase 3 clinical trials were completed and disclosed in December 2025.<ref name="Hebebrand2026">{{cite web | last=Hebebrand | first=Maddi | title=Clascoterone 5% Delivers Strong Phase 3 Hair-Growth Results | website=Dermatology Times | date=12 January 2026 | url=https://www.dermatologytimes.com/view/clascoterone-5-delivers-strong-phase-3-hair-growth-results | access-date=12 January 2026}}</ref> The drug significantly improved hair growth in both trials.<ref name="Hebebrand2026" /> More specifically, target area hair count (TAHC) had a relative improvement of 5.39-fold (539%) in one study and of 1.68-fold (168%) in the other study, both ''compared to placebo''.<ref name="Hebebrand2026" /> In other words, hair growth improved in both the placebo and clascoterone groups, but growth improved by about 1.7- to 5.4-fold more with clascoterone than with placebo.<ref name="Hebebrand2026" /> The actual absolute changes in hair counts in the different groups have not yet been released.<ref name="Hebebrand2026" />

===Other uses=== Clascoterone has been suggested as a possible treatment for hidradenitis suppurativa (acne inversa), an androgen-dependent skin condition.<ref name="Der_Sarkissian_2020">{{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 | article-number = e14142 | date = August 2020 | pmid = 32761708 | doi = 10.1111/dth.14142 | s2cid = 221036602 | doi-access = free }}</ref>

==See also== * List of investigational hair loss drugs * Pyrilutamide (KX-826) * GT-20029 (AR-PROTAC)

==References== {{Reflist}}

== External links == * {{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)}}

Category:Anti-acne preparations Category:Antiandrogen esters Category:Diketones Category:Pregnanes Category:Propionate esters Category:Steroidal antiandrogens