Tirabrutinib (Velexbru®) is an orally administered, small molecule, Bruton's 
tyrosine kinase (BTK) inhibitor being developed by Ono Pharmaceutical and its 
licensee Gilead Sciences for the treatment of autoimmune disorders and 
haematological malignancies. Tirabrutinib irreversibly and covalently binds to 
BTK in B cells and inhibits aberrant B cell receptor signalling in B 
cell-related cancers and autoimmune diseases. In March 2020, oral tirabrutinib 
was approved in Japan for the treatment of recurrent or refractory primary 
central nervous system lymphoma. Tirabrutinib is also under regulatory review in 
Japan for the treatment of Waldenström's macroglobulinemia and lymphoplasmacytic 
lymphoma. Clinical development is underway in the USA, Europe and Japan for 
autoimmune disorders, chronic lymphocytic leukaemia, B cell lymphoma, Sjogren's 
syndrome, pemphigus and rheumatoid arthritis. This article summarizes the 
milestones in the development of tirabrutinib leading to the first approval of 
tirabrutinib for the treatment of recurrent or refractory primary central 
nervous system lymphoma in Japan.