Clascoterone

Brand name: Winlevi®
Drug class: Topical androgen receptor (AR) antagonist

Mechanism of Action

Clascoterone is a steroidal androgen receptor blocker that works locally in the skin.

How it works:

Binds competitively to the androgen receptor (AR) in sebocytes (sebaceous gland cells) and hair follicle cells.
Blocks the action of dihydrotestosterone (DHT) and testosterone at these receptors.
This reduces sebum (oil) production and inflammatory signaling in the skin — two major factors driving acne.

Key idea:

It works like an antiandrogen (e.g., spironolactone), but only where it’s applied, with minimal systemic absorption.

Clinical Indication

Topical treatment of acne vulgaris in patients ≥12 years old.
Especially useful in hormone-driven acne, including:
- Adult female acne
- Acne resistant to topical retinoids/antibiotics

Pharmacology

Property	Description
Formulation	1% topical cream
Target	Androgen receptor (in sebocytes, keratinocytes)
Onset	Visible improvement in ~8–12 weeks
Metabolism	Rapidly converted in skin to cortexolone (inactive metabolite)
Systemic exposure	Minimal → few systemic side effects

Side Effects

Generally mild and local:

Erythema
Burning or stinging
Dryness
Rarely mild HPA-axis suppression (if large areas used)

Unlike oral antiandrogens:

No systemic hormonal effects (e.g., gynecomastia, menstrual irregularities).
No changes in serum testosterone or cortisol when used properly.

Mechanism Summary

Level	Effect
Molecular	Competitive AR antagonism
Cellular	↓ DHT-mediated gene activation in sebocytes
Tissue	↓ Sebum, ↓ inflammation
Clinical	↓ Acne lesion count, ↓ severity

Comparison to Other Antiandrogens

Drug	Route	Target	Use
Clascoterone	Topical	AR blocker (skin only)	Acne
Spironolactone	Oral	AR blocker + aldosterone antagonist	Hormonal acne, hirsutism
Flutamide / Bicalutamide	Oral	AR blocker	Prostate cancer
Finasteride / Dutasteride	Oral	5-α-reductase inhibitor	Androgenetic alopecia, BPH

In short:

Clascoterone = “Topical spironolactone” — a skin-targeted androgen receptor blocker that reduces sebum and inflammation in acne without systemic hormonal effects.

Summary of Clinical Studies with Clascoterone 1% Cream

Study (Year)	Design / N	Population	Duration	Key Efficacy Results (Week 12 unless noted)	Safety Findings
Hebert et al., JAMA Dermatol 2020CB-03-01/25 & /26 (Phase 3 RCTs)	2 RCTs, double-blind, vehicle-controlledn = 1,440 (adolescents/adults ≥9y)	Moderate-to-severe facial acne	12 weeks	IGA treatment success: 18.4% & 20.3% vs 9.0% & 6.5% (vehicle), p<0.001Inflammatory lesion ↓: −19.3 & −20.0 vs −15.5 & −12.6Non-inflammatory lesion ↓: −19.4 & −19.4 vs −13.0 & −10.8 (p<0.001)	AE rates similar to vehicle; mild local erythema/dryness most common
Mazzetti et al., J Drugs Dermatol 2019 (Phase 2b Dose-Ranging)	Randomized, vehicle-controlled, 5 arms (0.1%, 0.5%, 1% QD/BID, vehicle)n = 363	Moderate facial acne	12 weeks	Best regimen: 1% BIDInflammatory lesion ↓: −13.5Non-inflammatory lesion ↓: −17.5IGA success: highest in 1% BID arm	Well tolerated; no systemic AEs; mild local reactions
Eichenfield et al., JAAD 2020 (Open-label LTE)	Long-term open-label extensionn = 609 continued from Phase 3	Moderate-to-severe facial acne	Up to 9 months	Sustained lesion reductions from Week 12 maintained through Month 9	TEAEs 18.1%; mostly mild (nasopharyngitis, local erythema, dryness); no serious drug-related AEs
Eichenfield et al., J Drugs Dermatol 2024 (Integrated Analysis)	Pooled Phase 3 + LTE data	Adolescents/adults ≥12y with facial & truncal acne	Up to 12 months	Treatment success: ~30% (face) after 12 mo, ~32% (trunk) after 9 mo; continued lesion improvement over time	Safety consistent with pivotal trials
Bhatia et al., J Drugs Dermatol 2024 (HPA Axis Study)	Open-label, maximal use safety studyn = 69	Moderate-to-severe acne (face + trunk)	14 days	Not efficacy-focused	Mild reversible HPA-axis suppression in 5/69; no clinical adrenal insufficiency; cortisol normalized within 4 weeks

Abbreviations

IGA: Investigator’s Global Assessment (treatment success = clear/almost clear + ≥2-grade improvement)
TEAE: Treatment-emergent adverse event
BID: Twice daily
QD: Once daily

Table: Clascoterone vs Other Topical Acne Therapies — Key Clinical Results

Study / Drug	Design / N	Population	Duration	Key Efficacy Results (Week 12 unless noted)	Safety / Tolerability	Distinctive Features
Clascoterone 1% Cream (Winlevi)Hebert et al., JAMA Dermatol 2020	2 Phase 3 RCTs, n=1,440	Moderate–severe facial acne, ≥9y	12 wks	IGA success: 18–20% vs 6–9% (vehicle)Inflammatory lesion ↓: −19 to −20 vs −13 (vehicle)Non-inflammatory ↓: −19 vs −11 (p<0.001)	Mild, localized dryness/erythema; AE rates ≈ vehicle	First topical antiandrogen (DHT receptor blocker); no systemic hormonal effects; safe for both sexes
Tretinoin 0.05–0.1% (various RCTs)	Randomized, double-blind, vehicle-controlled	Mild–moderate acne	12–24 wks	Inflammatory lesion ↓: ~40–55%Non-inflammatory ↓: ~40–50%	Irritation, peeling, erythema common initially; improves with use	Keratolytic + comedolytic; cornerstone for comedonal acne; photosensitivity risk
Adapalene 0.1–0.3% (Thiboutot et al., 2006; others)	Multicenter RCTs, n≈1,200	Mild–moderate acne	12 wks	Lesion reduction: 45–60% overall; comparable or slightly less than tretinoin	Lower irritation than tretinoin; well tolerated	Synthetic retinoid; stable with benzoyl peroxide; OTC 0.1% available
Benzoyl Peroxide (BPO) 2.5–10% (multiple trials)	Randomized, vehicle-controlled	Mild–moderate acne	6–12 wks	Inflammatory lesion ↓: 45–70%; rapid onset (~1–2 wks)	Dryness, irritation, bleaching of fabrics	Antibacterial + anti-inflammatory; no resistance risk
Topical Dapsone 5% Gel (Lucky et al., 2007; Tanghetti, 2010)	Phase 3 RCTs, n≈3,000	Moderate acne, esp. females	12 wks	Inflammatory lesion ↓: −15 to −18 vs −12 (vehicle); modest overall	Well tolerated; dryness and oiliness mild	Useful for adult female acne; weak anti-inflammatory; safe for G6PD deficiency when topical
Clindamycin 1% (± BPO) (Eady et al., 2003; others)	Double-blind RCTs	Mild–moderate acne	12 wks	Lesion ↓: 45–60%; faster with BPO combination	Mild irritation; resistance risk when used alone	Combine with BPO to prevent C. acnes resistance

How Clascoterone Compares

Aspect	Clascoterone 1%	Retinoids (Tretinoin/Adapalene)	Antimicrobials (Clinda/BPO/Dapsone)
Primary Mechanism	Topical androgen receptor antagonist	Keratinization normalization	Anti-inflammatory / antibacterial
Onset of Action	Moderate (visible by week 8–12)	Slow (8–12 weeks)	Rapid (1–4 weeks)
Best For	Hormonal / sebaceous acne (both sexes)	Comedonal acne	Inflammatory papules/pustules
Systemic Risk	Minimal (no hormonal suppression in trials)	Minimal	Minimal; resistance risk (clinda)
Tolerance	Excellent; similar to vehicle	Moderate irritation	Mild dryness
Unique Advantage	First non-hormonal topical targeting androgenic pathway	Gold standard for comedonal acne	Quick inflammation control

Summary Takeaway:

Clascoterone 1% offers a novel mechanism—blocking androgen receptors in sebocytes—without systemic effects seen with oral antiandrogens (e.g., spironolactone).
Efficacy is modest but statistically significant vs vehicle, comparable to other monotherapies in mild–moderate acne.
Best positioned as part of combination regimens (e.g., with retinoid or BPO) to target multiple acne pathways.

References

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 Dermatology. 2020;156(6):621–630. doi:10.1001/jamadermatol.2020.0465. JAMA Netzwerk
Mazzetti A, Moro L, Gerloni M, Cartwright M. A Phase 2b, 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. PubMed
Eichenfield LF, Hebert A, Stein Gold L, et al. 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;83(2):477–485. PubMed
Eichenfield LF, Stein Gold L, Han J, et al. Integrated Short-Term and Long-Term Efficacy of Topical Clascoterone Cream 1% in Patients Aged ≥12 Years With Acne Vulgaris. J Drugs Dermatol. 2024;23(1):1278–1283. PubMed
Bhatia N, Eichenfield LF, Mazzetti A, et al. Hypothalamic-Pituitary-Adrenal Axis Response in Patients With Acne Vulgaris Treated With Clascoterone. J Drugs Dermatol. 2024;23(6):433–437. PubMed