Q&A With Maria Hordinsky, MD: How Clascoterone 5% Aims to Solve Decades of Unmet Needs in AGA

With positive phase 3 data from the SCALP1 (NCT05910450) and SCALP2 (NCT05914805) trials bringing renewed attention to clascoterone 5% topical solution, dermatologists may soon have access to the first novel mechanism of action for male androgenetic alopecia (AGA) in more than 3 decades. Following up on the latest findings, Dermatology Times spoke with Maria Hordinsky, MD, professor of dermatology at the University of Minnesota and clinical investigator in the program, who discusses how this mechanism differentiates clascoterone from existing treatments, unpacks the most clinically meaningful findings from the 12-month data, and explores how this potential therapy could reshape patient conversations and long-term management strategies in AGA.

Dermatology Times: How does clascoterone’s mechanism of action differ from other AGA therapies? Where do you see it fitting in the current treatment landscape?

Hordinsky: Clascoterone 5% topical solution works by directly targeting the androgen receptor within the hair follicle, competing with dihydrotestosterone [DHT] at the site where miniaturization occurs. This is distinct from minoxidil, which does not address androgen signaling, and finasteride, which reduces DHT systemically. I see it as a valuable addition, particularly for patients seeking a topical option that targets the underlying biology of AGA without systemic exposure, which is crucial for long-term use.

Dermatology Times: In your opinion, what were the most exciting and/or surprising findings from the recent 12-month phase 3 trial of clascoterone?

Hordinsky: The most compelling finding was the continued improvement in hair growth through month 12, rather than the plateau we often see with existing therapies. It was also notable that patients who stayed on treatment continued to gain benefit, while those who stopped saw a decline, reinforcing the importance of ongoing therapy.

Dermatology Times: One of the most significant findings was the absence of systemic hormonal adverse effects. Why is this important for long-term patient satisfaction, confidence, and adherence, especially compared with existing alopecia drugs?

Hordinsky: Concerns about systemic [adverse] effects, particularly sexual [adverse] effects, are a major barrier to treatment with existing therapies. One thing I often observe in my practice is that patients are hesitant to start treatment because of concerns about hormonal effects. A potential topical option—with no observed systemic hormonal adverse effects—can improve patient confidence and make them more likely to start and stay on treatment long term, which is critical to improving outcomes in AGA and helping men achieve their hair growth goals.

Dermatology Times: Although these trials focused on clascoterone monotherapy, is there any potential for it to be used in combination with existing treatments such as minoxidil or oral finasteride?

Hordinsky: Given its distinct mechanism of action, there is a strong rationale for combining clascoterone with other oral therapies. While combination use wasn’t studied in these trials, this is something that future trials could address. My patients often use a combination of the approved topical and oral therapies, and having an additional topical option that locally targets the underlying cause of hair loss in male AGA would give patients more choice in how they achieve their hair growth goals.

Dermatology Times: It’s been more than 30 years since a novel mechanism of action was introduced for male AGA. How could this potential approval change the conversation between dermatologists and their male patients once it hits the market?

Hordinsky: If approved, clascoterone 5% topical solution would meaningfully expand the conversation by offering a new type of treatment beyond the long-standing options. There has been no meaningful innovation in this therapeutic area for decades, and for those patients hesitant to start a treatment due to concerns about [adverse] effects or limited efficacy, this may reengage them.
I think it’s also important to note that even the approved options were not initially developed to treat hair loss—hair regrowth was noted as an “[adverse] effect” when finasteride and minoxidil were being developed for enlarged prostate and hypertension, respectively. Clascoterone 5% topical solution was intentionally designed to address the underlying biology of male AGA and is optimized for use in this indication.

Dermatology Times: Is there anything else you’d like to share that these questions did not address?

Hordinsky: I just want to reiterate that AGA remains an area of significant unmet need, with many patients dissatisfied with current options. Hair loss can have a significant negative impact on men’s self-confidence, stress levels, and social function, and helping men achieve their hair growth goals is essential for improving quality of life. The combination of novel targeted mechanism, favorable safety profile, and continued efficacy through 12 months suggests this could be an important new option for long-term management that delivers results patients want.