Approximately a third of patients with paroxysmal nocturnal hemoglobinuria (PNH) remain transfusion dependent or have symptomatic anemia despite treatment with a C5 inhibitor. Pegcetacoplan inhibits complement proximally at the level of C3 and is highly effective in treating persistent anemia resulting from C3-mediated extravascular hemolysis. We describe the rationale for C3 inhibition in the treatment of PNH and discuss preclinical and clinical studies using pegcetacoplan and other compstatin derivatives. We propose an approach for sequencing complement inhibitors in PNH.
© 2022 by The American Society of Hematology.