Brepocitinib in Phase 2/3 Trials: A Potential Breakthrough for Lichen Planopilaris

In a continuing conversation, Kristen Lo Sicco, MD, associate professor of dermatology at the Ronald O. Perelman Department of Dermatology at NYU Langone Health, discussed the clinical development of brepocitinib, an oral Janus kinase (JAK) inhibitor currently in phase 2/3 trials for lichen planopilaris (LPP).

The recently announced trial will focus on patients with moderate to severe disease, defined by both clinical symptoms such as pruritus, pain, burning, or dysesthesia, and objective signs of inflammation, including perifollicular erythema and scaling observed on clinical exam and trichoscopy. Disease severity is primarily measured using a validated, novel Investigator Global Assessment (IGA) specific to LPP, with treatment success defined as achieving quiescent or near-quiescent disease (IGA 0–1) alongside symptomatic improvement over a six-month treatment period. While the Lichen Planopilaris Activity Index (LPPAI) is included as a secondary endpoint, the IGA was specifically developed and validated to meet regulatory standards for potential FDA approval.

Lo Sicco emphasized the mechanistic rationale for JAK inhibition in LPP, noting that the JAK-STAT pathway plays a key role in the inflammatory cascade underlying this condition. Prior studies, including those evaluating topical JAK inhibitors in related disorders such as frontal fibrosing alopecia, support this therapeutic approach. The systemic administration of brepocitinib offers the potential to treat disease “from the inside out,” particularly in patients with more extensive or refractory disease. The drug has already shown success in other rare diseases such as dermatomyositis and cutaneous sarcoidosis.

Safety considerations were also addressed, particularly in light of boxed warnings associated with oral JAK inhibitors. Lo Sicco referenced a meta-analysis, which found no statistically significant increase in major adverse cardiovascular events or thromboembolic risk in dermatologic populations treated with JAK inhibitors, although she noted the importance of patient selection and the need for longer-term data.

Importantly, she highlighted the potential for brepocitinib to become the first FDA-approved systemic therapy for LPP, a milestone that could significantly improve treatment access and reduce delays associated with insurance approvals, an issue previously observed with JAK inhibitors in alopecia areata. She encourages clinicians to remain informed about emerging therapies and to utilize resources such as the Scarring Alopecia Foundation to support both patient education and clinical decision-making in this evolving space.

“I'm really hoping that the FDA approval will help to break down some barriers regarding timely insurance approval,” Lo Sicco concluded. “So that means a short period of time between me putting in the prescription and the patient actually getting the medication in their hands. Like we said, time is of the essence.”