Phase III Clascoterone Data Shows Sustained Hair Growth; Scalp SD Metabolomics Reveals Key Inflammatory Markers

Two developments in dermatological research highlight advances in scalp condition treatment and understanding. Cosmo Pharmaceuticals announced positive 12-month Phase III data for its Clascoterone 5% topical solution in male androgenetic alopecia, while a separate metabolomics study identified key molecular changes underlying scalp seborrheic dermatitis.

The Phase III program for Clascoterone, composed of the SCALP 1 and SCALP 2 pivotal studies, enrolled 1,465 subjects across 51 study centers in the United States and Europe, making it the largest Phase III clinical program ever conducted for a topical treatment in male androgenetic alopecia (AGA). The 12-month extension evaluated long-term safety and durability of effect in patients who were responders in the first 6-month study period.

Patients who remained on Clascoterone for the full 12 months achieved a statistically significant 2.39x improvement in Target Area Hair Count (TAHC) versus patients who received Clascoterone for six months and were then switched to vehicle from month 7 to month 12. Patients who stayed on Clascoterone kept improving, while patients who switched to the placebo from Month 7 onwards experienced a measurable decline in hair count. Clascoterone patients continued to gain hair from Month 3 to Month 12 with ongoing treatment. Subjects treated with Clascoterone for 12 months reported a statistically significant +24.5% relative improvement in treatment satisfaction versus vehicle groups.

Across 12 months of treatment, Clascoterone maintained a safety and tolerability profile comparable to vehicle, with no significant systemic hormonal side effects observed. These findings are consistent with the negligible systemic absorption previously seen in earlier clinical studies and support Clascoterone as a long-term treatment option appropriate for safe chronic use. The company said NDA and MAA preparations are underway, with U.S. filing planned for early 2027. Clascoterone topical solution is designed to locally inhibit androgen receptor signaling in the scalp, directly targeting one of the key biological drivers of follicle miniaturization — described as the first novel mechanism in over 30 years targeting the root cause of hair loss.

Meanwhile, a metabolomics study has provided new molecular-level characterization of scalp seborrheic dermatitis (SD), one of the most common inflammatory conditions of the scalp. Scalp SD chiefly concerns adults aged between 18 and 40 years and is characterized by a high level of sebum production, dandruff, flaking and scaling, associated with itching and irritancy. The condition is often chronic, with alternating acute and remission periods.

The study identified Malassezia fungi as playing a key role in the onset and exacerbation of SD, primarily through their high lipase activity, which leads to the release of irritating free fatty acids from hydrolysis of sebum triglycerides that trigger skin inflammatory response. Oleic acid and arachidonic acid were identified as the main lipids responsible for inflammation in SD. A high level of Malassezia colonization, along with high sebaceous secretion and specific individual factors, can disrupt the scalp ecosystem, compromise skin barrier function, and trigger skin inflammation.

The research was conducted as part of a clinical evaluation of an anti-SD shampoo containing a combination of two antifungal compounds — piroctone olamine and ciclopirox olamine — that act synergistically, along with a keratolytic compound (keluamid) and a soothing antioxidant agent (β-glycyrrhetinic acid). A randomized controlled study with subjects presenting mild-to-moderate scalp SD demonstrated good clinical efficacy and safety of the shampoo when used during a two-phase scalp-care scheme over 10 weeks, comprising an intensive phase of three times per week followed by a maintenance phase of once per week.

Analysis of changes in the scalp microbiome during product use showed that the formulation specifically contributed to rebalancing the scalp ecosystem, evidenced by a significant decrease in the most abundant Malassezia fungi along with repopulation of the scalp with low-abundant fungal genera. The prospective, two-center metabolomics trial (NCT06578962) was conducted from November 2020 to May 2021 at two centers in France, representing the first investigation of the scalp SD metabolome at the molecular level.