Complement C5 inhibitor crovalimab for the treatment of paroxysmal nocturnal hemoglobinuria

INTRODUCTION: Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal hematopoietic stem cell disease characterized by hemolytic anemia, bone marrow failure, and thrombosis. Some PNH patients carrying the C5 mutation (Arg885) show poor response to eculizumab and ravulizumab. AREAS COVERED: The US FDA approved PiaSky (crovalimab-akkz) on 20 June 2024, for use in adults or adolescents with PNH. It is a humanized anti-C5 monoclonal antibody, formerly known as SKY59. The main objective of this review is to examine the pharmacological properties of crovalimab and its clinical efficacy and safety. EXPERT OPINION: Crovalimab inhibits the cleavage of complement C5 into C5a and C5b by specifically binding to complement C5, thus preventing terminal complement-mediated intravascular hemolysis in patients with PNH. Based on the pivotal trials COMMODORE 1 and COMMODORE 2, crovalimab had clinical efficacy not inferior to that of eculizumab and exhibited good tolerability and safety, including in controlling hemolysis, avoiding transfusions, and reducing or maintaining lactate dehydrogenase levels. Additionally, crovalimab showed a favorable response in PNH patients carrying C5 variants, and the response in adolescents aged ≥ 13 years was similar to that in adults. Common adverse events associated with crovalimab include infusion-related reactions, respiratory tract infections, and Type III hypersensitivity reactions.