⚡30-year first for alopecia

Good morning — it’s Saturday, December 13, and we’re covering topline results from the largest topical androgenetic alopecia program to date, the first positive 52-week trial in dermatomyositis, and more.

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Clascoterone 5% solution may represent the first meaningful innovation in male androgenetic alopecia (AGA) in more than three decades, following Cosmo’s announcement of positive Phase 3 topline results.

The company reported findings from the identically designed Scalp 1 and Scalp 2 trials. Together they formed a 1,465-patient program, the largest Phase 3 effort ever conducted for a topical therapy in AGA.

Both studies met the primary endpoint. At Month 6, Scalp 1 showed a 539% relative improvement in target-area hair count versus vehicle, and Scalp 2 a 168% gain (both P < 0.05). The disparity in effect size between the trials may become clearer once the full dataset is available.

One trial’s patient-reported outcome endpoint reached statistical significance, while the other showed a positive trend; however, a pooled analysis across both trials was statistically significant and aligned with objective hair count improvements.

The solution was well tolerated, with adverse events comparable to vehicle.

Mechanistically, clascoterone is a first-in-class topical androgen receptor inhibitor designed to block dihydrotestosterone (DHT) at the hair-follicle receptor with minimal systemic absorption. It uses the same active ingredient as Winlevi, Cosmo’s FDA- and EMA-approved clascoterone 1% acne cream. According to the company, Winlevi is now the leading branded topical acne product in the US with over 1.4 million prescriptions since its 2021 launch.

For the AGA program, Cosmo expects to complete the 12-month safety follow-up in early 2026 before submitting parallel filings to the FDA and EMA. Company shares rose more than 30% following the announcement.

> Positive Phase 3 results from the longest and largest dermatomyositis trial: Roivant and Priovant reported that oral brepocitinib met the primary and all nine key secondary endpoints in the Phase 3 VALOR trial. The findings represent the first positive outcome for a 52-week placebo-controlled trial in dermatomyositis. The once-daily oral JAK1/TYK2 inhibitor was evaluated in 241 adults randomized to 30 mg, 15 mg, or placebo for 52 weeks. Approximately 75% entered the trial on background oral steroids (mean dose ~12 mg/day). At Week 52, patients receiving 30 mg achieved a higher mean Total Improvement Score (TIS; 0–100 scale) of 47 versus 31 with placebo (P = 0.0006). Separation from placebo was evident as early as Week 4. Efficacy was greater with the higher dose than with the lower dose. Compared with placebo, more patients receiving brepocitinib 30 mg also discontinued steroids entirely (42% vs 23%) and achieved cutaneous clinical remission (44% vs 21%). Brepocitinib was well tolerated. Adverse events of special interest, including malignancy, cardiovascular events, and thromboembolism, occurred no more frequently than with placebo. The companies plan to submit FDA filings in the first half of 2026.

> First Phase 3 OX40 inhibitor trials show efficacy in atopic dermatitis: Rocatinlimab outperformed placebo across all efficacy endpoints in moderate-to-severe atopic dermatitis, according to the Phase 3 ROCKET-IGNITE and ROCKET-HORIZON trials published in The Lancet. The monoclonal antibody functions as a T cell rebalancing therapy, selectively inhibiting and reducing pathogenic T cells by targeting the OX40 receptor. Investigators randomized 1,495 adults to subcutaneous rocatinlimab 300 mg, 150 mg (IGNITE only), or placebo every four weeks. Approximately one in five patients had previously received a biologic or systemic JAK inhibitor. At Week 24, EASI 75 (≥75% reduction in eczema severity) was achieved by 42% and 36% of patients on 300 mg and 150 mg in IGNITE, and by 33% on 300 mg in HORIZON, compared with 7–14% on placebo. Responses continued to increase from Week 16 to Week 24, suggesting that efficacy had not plateaued by trial end. Additionally, exploratory analyses showed selective reduction of OX40R-positive CD4+ T cells while preserving global CD4+ pools. Overall adverse and serious event rates were similar to placebo. Pyrexia (12%) and chills (2–6%) were the most common events in the active treatment arms, occurring primarily after the first injection. Notably, three cases of serious gastrointestinal ulceration were reported in the rocatinlimab arm. The accompanying editorial highlighted that both this safety signal and the drug’s apparently lower efficacy and slower onset than dupilumab may challenge clinical uptake.

> Apremilast shows early and sustained efficacy in palmoplantar pustulosis: A Phase 3 trial published in JEADV found that apremilast significantly improved disease severity in patients with moderate-to-severe palmoplantar pustulosis (PPP) and an inadequate response to topical therapy. Investigators randomized 176 Japanese adults to apremilast 30 mg twice daily or placebo for 16 weeks. This was followed by a 36-week open-label phase in which all patients received active treatment. By Week 16, 68% of patients on apremilast achieved PPPASI-50 (≥50% reduction in disease severity) compared with 35% on placebo, a 33-percentage-point difference (P < 0.0001). Improvements emerged as early as Week 2 and were maintained to Week 52. At that point, 73% of those originally assigned to apremilast remained PPPASI-50 responders. Safety was consistent with the drug’s known profile. More patients on the PDE4 inhibitor experienced at least one adverse event than on placebo (73% vs 49%). The most common events during the placebo-controlled period were diarrhea (19% vs 3%), headache (11% vs 2%), and nausea (11% vs 1%). No cases of depression occurred during the study. The PPPASI-50 advantage over placebo appears larger than that observed in Japanese trials of guselkumab (23%) and brodalumab (19%). However, indirect comparisons remain limited by differences in trial design, populations, and baseline disease severity.

Quizzes, cases, and perspectives to sharpen your clinical eye.

Long-term follow-up of the BRAVE-AA1/AA2 trials showed that baricitinib maintained efficacy over three years in adults with severe alopecia areata. At Week 152, 89% of patients on 4 mg and 84% on 2 mg sustained at least 80% scalp coverage (SALT ≤20). Adverse events of special interest remained stable with prolonged exposure (More)

The European Commission has approved dupilumab as the first targeted treatment in more than ten years for chronic spontaneous urticaria. The indication includes patients aged 12 years and older with moderate-to-severe disease who remain symptomatic despite antihistamines and who are naïve to anti-IgE therapy (More)

The FDA has approved the selective MEK1/2 inhibitor selumetinib (Koselugo) for adults with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas. The approval was based on the Phase 3 KOMET trial, which showed a 20% overall response rate, defined as at least 20% confirmed tumor shrinkage, by Cycle 16 compared with 5% for placebo. Among responders, 86% maintained tumor shrinkage for at least six months (More)

In a three-arm, double-blind randomized trial of 300 patients with warts, combining 44°C local hyperthermia with 3% hydrogen peroxide achieved complete clearance in 70% of patients at Week 24, compared with 53% for hyperthermia alone and 31% for hydrogen peroxide alone. Clearance rates were higher for condyloma acuminatum than for plantar and common warts. All adverse events were mild to moderate (More)

In a prospective study of 62 patients with stable lichen planus pigmentosus, low-fluence 1064-nm Q-switched Nd:YAG laser toning reduced the mean Modified Melasma Area and Severity Index (mMASI, range 0–24) score from 5 to 3 after four monthly sessions. At study end, 76% of participants achieved at least 25% improvement, and 26% experienced at least 50% improvement. No cases of post-inflammatory hyperpigmentation, scarring, or mottled hypopigmentation were observed (More)