New Hair Loss Treatment Safer than Finasteride: Clascoterone 5% Topical Solution

[Nelson Vergel]

Clascoterone 5% Topical Solution for Male Androgenetic Alopecia

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Overview​

Clascoterone 5% topical solution represents what could be the first genuinely novel therapeutic mechanism for male pattern hair loss in over three decades. Cosmo Pharmaceuticals announced breakthrough topline results from its two pivotal Phase III trials (SCALP-1 and SCALP-2) on December 3, 2025, marking a potential first major therapeutic breakthrough in hair-loss treatment in more than thirty years.
The drug is being developed under the brand name Breezula for androgenetic alopecia (AGA). The 1% cream formulation is already FDA-approved as Winlevi for acne vulgaris (August 2020), and the higher 5% concentration is now being pursued for hair loss specifically.

Mechanism of Action​

Clascoterone works fundamentally differently from existing AGA treatments through direct androgen receptor antagonism.

Androgen Receptor Antagonism​

Clascoterone is a steroidal antiandrogen, or antagonist of the androgen receptor (AR), the biological target of androgens such as testosterone and dihydrotestosterone (DHT). In bioassays, the topical potency of the medication was greater than that of progesterone, flutamide, and finasteride and was equivalent to that of cyproterone acetate.
The drug functions as an androgen receptor inhibitor to counteract the androgenic effects of DHT in the skin. It competes with DHT for the androgen receptors in the sebaceous glands of hair follicles and in dermal papilla cells.

Key Distinction from Finasteride​

Finasteride lowers overall DHT levels in the body by blocking its production through inhibiting an enzyme, while clascoterone works by preventing DHT from binding to androgen receptors. This is critical: finasteride reduces systemic DHT by approximately 70%, affecting the entire body, while clascoterone acts locally at the follicle without significant systemic absorption.

Minimal Systemic Exposure​

Clascoterone is rapidly hydrolyzed by skin and plasma esterases to its inactive form, cortexolone, minimizing its systemic anti-androgenic effects. The drug is designed to exert strong antiandrogenic activity locally while being rapidly deactivated once absorbed, essentially creating a "topical-only" effect.

Phase III Trial Results (SCALP-1 & SCALP-2)​

Study Design​

A total of 1,465 patients were randomized into the two identical-in-design clinical studies Scalp 1 (NCT05910450) and Scalp 2 (NCT05914805). These represent the largest Phase III program ever conducted for a topical AGA treatment.
• Duration: 6 months (with ongoing 12-month safety follow-up)
• Application: Twice daily
• Participants: Men over 18 with mild-to-moderate AGA
• Sites: U.S. and Europe (~60 centers)

Primary Endpoints​

Both studies reached statistically significant endpoints in TAHC (Target-Area Hair Count), with one reaching 539% relative improvement to placebo and the second study reaching 168% relative improvement to placebo.

Understanding the Disparity​

The difference in the trial figures is driven "entirely by baseline hair counts, not by a difference in drug performance," according to Cosmo CEO Giovanni Di Napoli. When the two groups experience a similar absolute increase in hair count but start from different baselines, the study with lower baseline values will show a larger relative percentage.

Patient-Reported Outcomes​

Patient-reported outcomes further reinforced the strength of the topline results, with one study reaching statistical significance and the other showing a positive trend. This alignment between objective measurements and patient perception is particularly relevant for a condition where self-image drives treatment adherence.

Safety Profile​

Topline Safety Data​

Treatment-emergent adverse events (TEAEs) were similar across both studies, and similar to placebo, with most TEAEs not related to clascoterone. Across both trials, treatment-related adverse events were similar to placebo. Most side effects were mild and not linked to the drug. No meaningful hormonal disturbances were seen.

Sexual Side Effects​

No sexual side effects were reported. For men who are concerned about systemic hormonal effects, clascoterone 5% topical solution will provide a topical option that addresses hair loss safely and effectively.
This is the potential game-changer: DHT is a key driver behind male-pattern baldness. Existing drugs reduce it throughout the body, which is why side effects such as sexual dysfunction often discourage use. Clascoterone targets the follicle directly.

Known Concerns from Acne Studies​

From the 1% cream data for acne:
• Clascoterone is metabolized to cortexolone which has weak glucocorticoid effects
• Reversible hypothalamic–pituitary–adrenal (HPA) axis suppression was observed 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
• HPA axis suppression was observed to occur in 3 of 42 (7%) of adolescents and adults using clascoterone for acne

Local Side Effects (from Winlevi data)​

Most common adverse reactions occurring in 7 to 12% of patients are erythema/reddening, pruritus and scaling/dryness. Additionally, edema, stinging, and burning occurred in >3% of patients.

Important Caveat​

The acne FDA label is for 1% whereas the SCALP1/2 hair loss trials used 5%. The full 12-month safety data will be critical to assess higher-dose implications.

Comparison with Existing Treatments​

Clascoterone 5% vs. Finasteride (Propecia)​

Aspect​	Finasteride​	Clascoterone 5%​
Mechanism	5α-reductase inhibitor	Androgen receptor antagonist
Site of action	Systemic (whole body)	Local (scalp follicles)
DHT effect	Reduces production ~70% systemically	Blocks binding at follicle
Sexual side effects	2-5% (per clinical data)	None reported in Phase III
Administration	Oral, once daily	Topical, twice daily
FDA status for AGA	Approved (1997)	Not yet approved

vs. Minoxidil (Rogaine)​

Minoxidil works through a completely different mechanism than either finasteride or clascoterone. It stimulates hair follicles through vasodilation and other effects not related to hormones. This makes minoxidil complementary to DHT-blocking approaches. Combination therapy with minoxidil may prove beneficial since they address different pathways.

Regulatory Pathway & Timeline​

Current Status​

Cosmo plans to complete the required 12-month safety follow-up by spring 2026, after which parallel FDA and EMA submissions are expected.

Projected Timeline​

1. Spring 2026: 12-month safety data completion
2. 2026: NDA/MAA submissions to FDA and EMA
3. Late 2026 / Early 2027: Potential approval (estimated)

Pharmacokinetics Summary​

• Protein binding: 84-89%
• Steady state: Achieved within 5 days of twice-daily application
• Primary metabolite: Cortexolone (11-deoxycortisol) - inactive
• Systemic absorption: Minimal when applied topically
In rodents, clascoterone has been found to possess strong local antiandrogenic activity, but negligible systemic antiandrogenic activity when administered via subcutaneous injection.

Clinical Relevance for Men's Health​

Ideal Candidates​

Clascoterone represents a promising potential addition to the treatment toolbox, especially for:
• Men who are hesitant to use or cannot tolerate oral finasteride or dutasteride
• Patients who prefer a topical, scalp-focused approach to androgen control
• Individuals already on multi-therapy regimens who may benefit from another mechanism targeting DHT at the follicle level

Combination Potential​

Given its distinct mechanism, clascoterone could theoretically be combined with:
• Minoxidil (different mechanisms, complementary)
• Low-dose oral finasteride (addressing DHT at both production and receptor levels)
• PRP therapy
• Low-level laser therapy

Limitations & Outstanding Questions​

• Full data not yet published – Only topline results available; detailed subgroup analyses pending
• Women excluded – Only men studied in Phase III; female pattern hair loss data limited
• Long-term durability unknown – 6-month efficacy data; longer-term maintenance unclear
• Pricing not established – Will likely be premium priced
• Twice-daily application – May affect adherence compared to once-daily alternatives

Bottom Line​

Clascoterone 5% topical solution represents a genuinely novel approach to AGA treatment – the first new mechanism in over 30 years. Its ability to block DHT at the follicular level without systemic absorption could address the primary concern that keeps many men from pursuing pharmacological hair loss treatment: fear of sexual side effects.
Expert Opinion: "For decades, patients have had to choose between available treatment options with limited efficacy or safety issues due to systemic hormonal exposure. These findings show the potential for clascoterone 5% topical solution to change that equation by delivering real, measurable regrowth with negligible systemic exposure." – Maria Hordinsky, MD, University of Minnesota
For men's health communities, this represents an important development worth following – particularly for men who have avoided finasteride due to concerns about hormonal side effects but would consider a topical option that works through direct receptor blockade rather than systemic DHT suppression.

Note: This document is based on Phase III topline results announced December 3, 2025. Full peer-reviewed data pending publication. Clascoterone 5% solution is not yet FDA-approved for androgenetic alopecia.

 

[Nelson Vergel]

More information:

Thread 'Clascoterone: Approval for Acne and Alopecia'

Oct 9, 2020

Abstract

Clascoterone (Winlevi®) is an androgen receptor inhibitor being developed as a topical cream and solution by Cassiopea (a spin-out company of Cosmo Pharmaceuticals) for the treatment of androgen-dependent skin disorders, including androgenetic alopecia and acne vulgaris. Although the exact mechanism of action of clascoterone for the topical treatment of acne vulgaris is unknown, the drug is believed to compete with the androgen dihydrotestosterone for binding to androgen receptors in the sebaceous gland and hair follicles to attenuate signaling necessary for...

• madman
• clascoterone treatment: acne/hair loss
• Replies: 7
• Forum: Testosterone Side Effect Management

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[Nelson Vergel]

More details: Game Changer: First Topical Androgen Receptor Inhibitor Targets Root Cause of Hair Loss — Clascoterone 5% Breakthrough After 30 Years - Excel Male Health Forum