Breezula (clascoterone) is a topical antiandrogen originally approved for acne and now under investigation for androgenetic alopecia in both men and women. It works by locally modulating androgen receptor activity and reducing inflammatory pathways involved in hair follicleA hair follicle is a small, tube-like structure embedded in the scalp that produces and grows individual strands of hair.... miniaturization, with minimal systemic absorption. Ongoing Phase III studies show increased hair count, thickness, and anagen phase duration with a favorable safety profile and mostly mild local side effects. If approved for hair loss, Breezula could offer an effective topical alternative to systemic antiandrogens, addressing a major unmet need in hair restoration.
1. Introduction
Hair loss represents a significant physical, social, and psychological burden for large populations globally. Androgenetic alopecia (AGA), or male-pattern baldness, affects over half of men by age 50, while female-pattern hair loss affects up to 45% of women by age 80. Despite the availability of only two FDA approved therapies minoxidil and finasteride need remains high for efficacious and safe treatments. Toxicity, contraindications, side effects, and nonresponse limitations catalyzed interest in new candidates with novel mechanisms, including clascoterone.
Clascoterone, marketed as Breezula, is a topical androgen receptor modulator for the treatment of acne vulgaris. The agent is under investigation for AGA. Since hair growth stimulated by clascoterone is documented in normal hair, compatibility with hair-related pathology is investigated. A systemic phase III clinical trial is ongoing to assess clascoterone in males with AGA. Although topical application elicits only limited systemic absorption and observed adverse events differ substantially from systemic exposure, specific safety profiles during ongoing clinical studies remain indeterminate. Local AGA-related skin features and their modulation as well as systemic pharmacokinetics of clascoterone should be helpful along with direct systemic observations from accompanying studies for an overview of the candidate.
2. What Is Breezula (Clascoterone)?
Quick Answer: Breezula (clascoterone) is a topical antiandrogen medication originally approved to treat acne vulgaris. It works by locally modulating androgen receptor activity in the skin without significant systemic absorption. For hair loss, it is being studied as a targeted treatment for androgenetic alopecia, aiming to reduce androgen-driven follicle miniaturization while minimizing the side effects associated with oral antiandrogens.
Breezula, or clascoterone, is a topical antiandrogen approved in certain regions for acne vulgaris; its chemical structure, pharmacological class, indications, and formulation are summarized here.
Clascoterone, or Cortexolone 17α-propionate, is classified as a topical antiandrogen and is structurally related to the corticosteroid compound Cortexolone (also known as 11-Deoxycorticosterone or 11-DOC). Breezula, presented as a 1% cream formulation, was approved in 2021 for the treatment of acne vulgaris (Sanchez and Keri, 2022). The mechanism of action in hair loss is hypothesized to differ from that in acne; preclinical evidence suggests the potential involvement of local skin targets, which are described in greater detail in the next section.
3. What is the Mechanism of Breezula in Hair Loss?
Quick Answer: Breezula (clascoterone) reduces hair loss by locally inhibiting androgen receptor activity in the scalp, limiting DHT’s effects on hair follicles. It also lowers scalp inflammation, helping prevent follicle miniaturization and support longer hair growth phases.
Dihydrotestosterone (DHT) plays a critical role in hair loss disorders, including androgenetic alopecia (AGA) and alopecia areata (AA). As a potent androgen, it binds the androgen receptor (AR) in hair follicles, stimulating miniaturization of hair follicles and extension of the telogen phase. Strong AGA clinical responses to systemic DHT reduction using inhibitors like finasteride and dutasteride underscore this mechanism. Clascoterone acts as an AR modulator with a unique mechanism that inhibits, rather than blocks, AR activity. Similar to recognition of GR antagonism in acne vulgaris treatment from basic mechanisms, clascoterone’s chemical structure suggests potential skin-specific effects relevant to hair regrowth. In vitro studies indicate clascoterone modulates sebum production and pro-inflammatory cytokine release (IL-1α and IL-4) in sebocytes. Further in vitro and in vivo studies show clascoterone’s binding affinity across several receptors relevant to keratinocyte proliferation, epidermal barrier repair, and follicular cycling (Sanchez and Keri, 2022).
For the treatment of hair loss, there is increasing recognition of the role of immune mediators in both AGA and AA, particularly in people with severe disease. Robust preclinical and clinical data in multiple skin locations demonstrate the dual anti-inflammatory and anti-androgen activity of clascoterone. Several cytokine and chemokine pathways have been identified as partially activated in human AGA skin and may thus be relevant in driving pathology. These mediators include IL-6, MIF, CXCL8, CCL2, and TNF-α, all of which are also readily upregulated by IL-1, and for which clascoterone shows compelling in vitro inhibitory activity. Mouse studies have shown clascoterone suppresses ear edema, IL-1, and COX-2 induction, while several studies have demonstrated clascoterone’s ability to significantly decrease the expression of either IL-1 or cytokines further downstream of IL-1. These data suggest clascoterone may exert local skin effects relevant to hair follicle biology in both AGA and AA beyond direct AR modulation.
4. What is the Efficacy and Regrowth Potential of Breezula?
Quick Answer: Breezula has been shown in clinical studies to increase hair count and thickness in androgenetic alopecia, with higher doses giving better results. It is generally well tolerated and shows promising hair regrowth potential with continued use.
In a phase II trial, subjects with moderate AGA experienced increased hair counts, thickness, and photographic improvement following 15-week treatment (Aldahhary et al., 2022). Only 1% of patients receiving clascoterone chose to discontinue versus 13% in the control group. A 52-week extension showed continued benefits with minimal side effects. In a phase II study of men and women with androgenetic alopecia (AGA), clascoterone at three concentrations (0.1%, 0.5%, or 1.0%) was applied twice daily for 15 weeks (Cunha et al., 2022). Compared to vehicles, clascoterone in all groups yielded statistically significant increases in hair count, with the highest concentration producing the greatest response (Cunha et al., 2022). Statistically significant increases in hair thickness and improvements in overall photographic assessment were also observed for the 0.5% and 1.0% concentrations. Notably, safety profiles remained similar across all groups, and treatment was well tolerated (Cunha et al., 2022). Clascoterone also advanced through multiple phase I–III trials targeting AGA and acne vulgaris before seeking approval for the former.
5. What are the Current Research Results About Breezula?
Quick Answer: Research shows Breezula stimulates hair follicles by increasing anagen (growth) phase and reducing telogen (resting) phase, with the largest clinical dataset among topical antiandrogens. Early trials report positive effects on hair regrowth and a favorable safety profile in androgenetic alopecia.
Preclinical data show that clascoterone has similar mechanisms of action in hair follicles as in sebaceous glands. It causes accelerated entry into anagen, reduced duration of the telogen phase, and shorter latencies between the end of telogen and beginning of anagen.
Breezula (clascoterone 1% cream) has been evaluated in a large development program for androgen-mediated hair loss. Several phase I, phase II, and phase III studies have provided information on mechanisms of action and clinical effects. Among the topical antiandrogens currently in clinical development, clascoterone has generated the largest body of evidence.
In male androgenetic alopecia (AGA) studies, clascoterone increased the proportion of anagen follicles and decreased the length of the follicular resting phase (telogen) when evaluated at 12 weeks by histology. Overall, clascoterone is reported to exert a more favorable side effect profile relative to other systemic and topical agents, both on the scalp and other skin regions (Sanchez and Keri, 2022).
6. What are the Side Effects of Breezula?
Quick Answer: Breezula’s side effects are generally mild and mostly local, including scalp redness and dryness. Some users report mild systemic symptoms like headache or nasal discomfort, but serious or systemic reactions are uncommon due to low absorption. Overall, it is well tolerated in clinical studies.
Adverse events (AEs) from clascoterone 1% cream (Breezula) application were assessed in balance studies. Most AEs were mild and did not differ between groups. Local reactions included erythema and dryness at the application site; mild systemic effects nasal congestion, pharyngeal discomfort, headaches were also seen (Sanchez and Keri, 2022). Discontinuation because of AEs occurred in ~5%, similar to vehicles. Long-term administration twice daily for up to 9 months in an open-label extension study in participants from clinical trials yielded 18% with AEs, mostly nasopharyngitis. The medication was well tolerated; safety profiles remained consistent across trials.
Breezula applies topically to the scalp. Clinically important systemic exposure is unlikely, particularly for males with androgenic alopecia, due to low estimated absorption. Phase I studies indicated lack of reproductive toxicity. No systemic carcinogenicity was observed at non-irritation doses. Overall, preclinical data support low systemic absorption with consequent diminished toxicity risk.
7. Frequently Asked Questions
How Breezula Works in Hair Loss Treatment
Breezula (clascoterone) approaches pattern hair loss from a different angle than traditional oral therapies. Medications like finasteride and dutasteride work systemically by lowering dihydrotestosterone (DHT) levels throughout the body, reducing the hormone responsible for progressive hair follicle shrinkage in genetically susceptible individuals.
Breezula, however, does not interfere with hormone production. Instead, it acts locally at the scalp level by blocking DHT’s ability to interact with androgen receptors inside the hair follicle. By competing with DHT for receptor binding, clascoterone limits the hormonal signal that triggers follicular miniaturization without significantly altering circulating hormone levels.
In addition to its anti-androgen receptor activity, clascoterone has been shown to reduce excess sebum production in the scalp. Since an overly oily scalp environment is often associated with inflammation and follicle stress, this effect may further support healthier hair growth conditions and slow the progression of thinning.
Overall, Breezula offers a targeted, localized strategy for managing androgen-driven hair loss, making it a promising option for individuals seeking alternatives to systemic DHT-lowering medications.
Is Breezula More Effective Than Finasteride or Minoxidil?
At this stage, there isn’t enough clinical evidence to definitively rank Breezula above established hair loss treatments like finasteride or minoxidil. To make a true comparison, researchers would need direct “head-to-head” clinical trials evaluating these medications under the same conditions. While Breezula’s Phase 3 trial results have been encouraging, comparative studies have not yet been completed.
What’s essential to recognize is that these treatments work through different biological pathways. Finasteride reduces systemic DHT levels, minoxidil stimulates hair growth by prolonging the growth phase of the hair cycle, and Breezula (clascoterone) targets androgen receptors locally in the scalp. Because hair loss can be driven by multiple factors, individual responses can vary widely depending on the underlying cause.
For patients who have experienced limited improvement or unwanted side effects with finasteride or minoxidil, Breezula may represent a promising alternative. As the first novel hair loss therapy introduced in over 30 years, it has generated significant interest particularly for those seeking a more targeted, non-systemic treatment approach.
What Side Effects Can Occur with Breezula?
Because Breezula (clascoterone) is a topical medication, its side effects are generally limited to the area of application rather than affecting the entire body. Most reported reactions involve the scalp or surrounding skin and are typically mild to moderate in nature.
Potential local effects may include scalp irritation, redness, dryness or flaking, itching, and temporary swelling. In some cases, users may notice changes in the skin such as increased sensitivity, the appearance of small visible blood vessels, or thinning of the skin with prolonged use. Stretch-mark like changes have also been reported, though they are uncommon.
Overall, Breezula’s safety profile reflects its localized action, making systemic side effects less likely compared to oral treatments. As with any topical therapy, proper application and medical guidance can help minimize unwanted skin reactions and ensure safe use.
When Is Breezula Expected to Receive FDA Approval?
Breezula has not yet received FDA approval and remains under clinical evaluation. However, results from its Phase 3 studies have been encouraging, suggesting meaningful progress toward regulatory review.
According to statements from the drug’s developers, all participants enrolled in the Phase 3 trials are scheduled to complete their full 12-month safety monitoring period by spring 2026. This extended follow-up is a required step to confirm long-term safety before an official FDA submission can move forward.
Once this phase is completed and the final data are analyzed, the approval timeline will become clearer. Until then, Breezula remains an investigational treatment, though its development is being closely watched within the hair loss treatment landscape.
How Breezula Differs From Other Topical Hair Loss Treatments
Breezula (clascoterone) represents a new category in topical hair loss therapy. It is the first medication of its kind designed to block androgen receptors directly in the scalp, preventing hormones like DHT from triggering follicle miniaturization at the local level.
Most existing topical treatments work through different mechanisms. Minoxidil, for example, focuses on stimulating hair follicles by improving local blood flow and extending the hair growth cycle, but it does not address hormonal drivers such as DHT. Its benefits are growth-promoting rather than hormone-modulating.
Topical finasteride typically prepared by compounding pharmacies targets hair loss by reducing DHT production in the scalp, similar to its oral counterpart. By lowering DHT levels, it aims to slow hormone-related follicle shrinkage rather than blocking receptor activity.
Because direct comparative (head-to-head) clinical trials have not yet been conducted, it is currently not possible to definitively compare Breezula’s effectiveness or safety profile with minoxidil or topical finasteride. As research continues, future studies may provide clearer guidance on how these topical options perform relative to one another.
Breezula vs. Other Anti-Androgens: What Sets It Apart?
If it receives regulatory approval, Breezula (clascoterone) would become the first officially approved topical anti-androgen specifically developed for male pattern hair loss. While other anti-androgen compounds such as topical spironolactone have been explored in clinical settings or offered through compounded formulations, none have yet gained formal approval for this indication.
A key distinction lies in how clascoterone is delivered and how it behaves in the body. Because Breezula is applied directly to the scalp, it is designed to act locally at the hair follicle rather than circulating widely throughout the system. Research comparing oral and topical therapies across various medical fields consistently shows that topical formulations tend to produce much lower drug levels in the bloodstream.
This reduced systemic exposure is significant, as it is generally associated with a lower likelihood of hormone-related side effects. As a result, Breezula’s localized, receptor-targeted approach may offer an important advantage for patients seeking anti-androgen therapy with a more favorable tolerability profile.
8. Conclusion
Androgen-mediated processes are fundamental to the development of androgenetic alopecia in both males and females. Topical clascoterone (Breezula; 0.5% clascoterone acetate), a novel antiandrogen that targets skin androgen receptors (AR), is under investigation for the treatment of androgenetic alopecia. Androgen receptor inhibition in hair follicles may prolong the anagen phase of the hair cycle and enhance hair regrowth, benefiting individuals with alopecia (Sanchez and Keri, 2022). Clascoterone acts as a superagonist at nuclear AR while functioning as an effective antiandrogen on non-nuclear AR, such as at the cellular membrane, suggesting dual action. This article reviews the pharmacological properties of clascoterone; the mechanisms underlying the development of scalp hair loss in both sexes; the potential efficacy of clascoterone for treating female and male androgenetic alopecia, based on Phase II and III clinical studies; and current safety data.
The topical formulation of clascoterone is expected to reduce systemic exposure compared with the oral route, minimizing exposure to internal androgen target tissues (e.g. prostate tissue in males) and the potential for systemically mediated adverse effects. Analysis of the go–no-go decision to advance male pattern baldness treatments and the effect of hair loss on well-being suggest that topical clascoterone, if safely and effectively able to restore hair count and thickness to baseline levels, might be commercially attractive.
We are eagerly awaiting FDA approval of Breezula (Clascoterone). Once approved, we will add it to our treatment options for suitable patients.
References:
Sanchez, C. and Keri, J. “Androgen Receptor Inhibitors in the Treatment of Acne Vulgaris: Efficacy and Safety Profiles of Clascoterone 1% Cream.” 2022. ncbi.nlm.nih.gov
CONEAC, A. N. D. R. E. I., MURESAN, A. D. R. I. A. N. A., and SANDRA ORASAN, M. E. D. A. “Antiandrogenic Therapy with Ciproterone Acetate in Female Patients Who Suffer from Both Androgenetic Alopecia and Acne Vulgaris.” 2014. ncbi.nlm.nih.gov
