A phase 2a trial of brepocitinib for cicatricial alopecia
Eden David, Neda Shokrian, Ester Del Duca, Marguerite Meariman, Celina Dubin, Kelly Hawkins, Elizabeth Andrews, Savina Sikand, Giselle Singer, Barry S. Oemar, Yeriel Estrada, Swaroop Bose, Juliana Pulsinelli, Ping Mahling, Joel Corrêa da Rosa, Benjamin Ungar, Elena Peeva, Emma Guttman‐Yassky
Abstract
BACKGROUND: Cicatricial alopecias are chronic, progressive scarring hair-loss conditions. Molecular dysregulation is not fully understood, hindering treatment development. Th1/IFNγ signaling and Janus kinase dysregulation has shown involvement, providing rationale for this phase 2a trial with Tyrosine kinase 2/Janus kinase 1 inhibitor brepocitinib. METHODS: Randomized, placebo-controlled phase 2a trial spanning 52 weeks. Adults (≥18 years of age) with lichen planopilaris, frontal fibrosing alopecia, or central centrifugal cicatricial alopecia diagnosis were randomized 3:1 to brepocitinib 45 mg daily or placebo for 24 weeks, after which all patients received brepocitinib for another 24 weeks, with a safety follow up 4 weeks later. Lesional scalp biopsies were collected at baseline, week 24, and week 48. Coprimary endpoints were changes in lesional expression of C-C motif chemokine ligand (CCL5), changes in lesional expression of fibrosis-related markers, and safety at week 24. RESULTS: Patients receiving brepocitinib showed significant downregulation in CCL5 expression at week 24 (P = .004). Enrichment analysis of a subset of fibrosis markers showed trending upregulation in placebo patients (P < .1). Brepocitinib was well tolerated and improved clinical severity scores. LIMITATIONS: Single-dose regimen, small placebo group. CONCLUSION: Brepocitinib significantly reduces CCL5 expression and was well tolerated at week 24, meeting coprimary endpoints. Brepocitinib reduces inflammatory biomarker expression and improves clinical severity, while maintaining favorable safety profile.