Ritlecitinib

Ritlecitinib (PF-06651600) is a highly selective inhibitor of Janus kinase 3 (JAK3) and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family. In June 2023, it was approved by the FDA for the treatment of severe alopecia areata in adults and adolescents 12 years and older. It was further approved by the EMA in September 2023. Ritlecitinib is administered orally and is the first member of its class.

Ritlecitinib binds covalently to Cys-909 of JAK3, a site where other JAK isoforms have a serine residue. This makes ritlecitinib a highly selective and irreversible JAK3 inhibitor. Other kinases have a cysteine at a position equivalent to Cys-909 in JAK3, and several of them belong to the TEC kinase family. It has been suggested that the dual activity of ritlecitinib toward JAK3 and the TEC kinase family block cytokine signaling as well as the cytolytic activity of T cells, both implicated in the pathogenesis of alopecia areata.

Ritlecitinib is indicated for the treatment of severe alopecia areata in adults and adolescents 12 years and older. It is not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, cyclosporine or other potent immunosuppressants.