ALBERT

Description: Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by intravascular hemolysis and venous thrombosis. Deficiency of the terminal complement inhibitor CD59 from PNH red cells results in complement-mediated hemolysis. Eculizumab, a humanized monoclonal antibody that inhibits terminal complement by binding to C5, is effective at controlling intravascular hemolysis in PNH. We now report that 10 of the 11 patients from an initial 3 month study have continued to receive 900mg eculizumab every other week for 2 years. The remaining patient stopped eculizumab after 23 months despite effective control of intravascular hemolysis, as the patient continued to be transfused even after erythropoietin therapy. This patient had the most severe hypoplasia at the start of eculizumab therapy with a platelet count below 30x109/l, suggesting that the ongoing transfusions were due to the bone marrow failure and not continuing hemolysis. Eculizumab was safe and well tolerated with two reported SAEs in the last year, neither of which were attributed to the drug. The dramatic improvement in various parameters of hemolysis persisted during the 2 year treatment period for all patients. Mean LDH levels decreased from 3111 +/− 598 U/L over the 12 months prior to treatment to 634 +/− 34 U/L up to 24 months following treatment (p=0.002). PNH red cells with a complete deficiency of GPI-linked proteins (Type III red cells) progressively increased during the treatment period from a mean of 36.7% to 58.9% (p=0.001) while partially deficient PNH red cells (Type II) increased from 5.3% to 8.7% (p=0.01). There has been no change in the proportion of PNH neutrophils in any of the patients during eculizumab therapy indicating that the increase in the proportion of PNH red cells is due to a reduction in hemolysis and transfusions rather than a change in the PNH clone(s) itself. The mean and median transfusion rates decreased from 2.1 and 1.8 units/patient/month to 0.4 and 0.3 units/patient/month respectively (p