[Novel therapeutics for paroxysmal nocturnal hemoglobinuria]

Following the reports of paroxysmal nocturnal hemoglobinuria (PNH) due to PIGT and PIGB gene mutations, the definition of PNH was changed to a hematopoietic stem cell disease with complement-mediated intravascular hemolysis as a result of clonal expansion of hematopoietic stem cells with mutations in genes involved in glycosylphosphatidylinositol (GPI) anchor synthesis, including PIGA. Treatment with eculizumab (Soliris^®), a humanized anti-C5 monoclonal antibody, significantly improved the quality of life in patients with PNH, remarkably reduced hemolysis, improved symptoms associated with hemolysis, and prevented thrombosis. Although the administration interval has been extended and convenience has been greatly improved using the technique of recycling antibodies (ravulizumab and crovalimab), extravascular hemolysis has become another issue. Although attempts have been made to overcome this issue with proximal complement (C3, factor D, and factor B) inhibitors, the optimal therapeutic agent is expected to be selected after evaluating for not only efficacy and safety but also convenience.