Brepocitinib (Lisraya®), a first orally administered small molecule dual TYK2/JAK1 inhibitor approved for dermatomyositis in adults.

完整摘要 · 英文原文

Dermatomyositis is a rare systemic autoimmune disease characterized by chronic inflammation, progressive muscle weakness, and prominent cutaneous manifestations, with limited approved treatment options. Brepocitinib (Lisraya®), an orally administered dual tyrosine kinase 2 (TYK2) and Janus kinase 1 (JAK1) inhibitor, received the U.S. Food and Drug Administration approval on August 27, 2026, for the treatment of dermatomyositis in adults. Unlike broader JAK inhibitors, brepocitinib exhibits preferential activity against JAK1 and TYK2 over JAK2 and JAK3, providing a differentiated kinase-selectivity profile. In the phase 3 VALOR trial, once-daily brepocitinib 30 mg significantly improved the Total Improvement Score and multiple measures of dermatomyositis disease activity compared with placebo. Its approval highlights the successful application of kinase-directed medicinal chemistry to a rare autoimmune disease and provides a new oral therapeutic option for adults with dermatomyositis. Brepectinib molecule structure is shown inhibiting two proteins labeled TYK2 and JAK1, with red bars indicating TYK2 and JAK1 inhibition.