Eculizumab: A novel therapy for paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease caused by a somatic mutation of the PIGA gene, which results in the absence of the glycosylphosphatidylinositol-linked proteins necessary to protect cells from complement-mediated lysis. The primary clinical manifestations of PNH include intravascular hemolytic anemia, thrombosis in vessels, and bone marrow failure, which can cause pancytopenia. Treatment of PNH has been largely symptomatic until the development of eculizumab, a monoclonal antibody to the C5 complement protein. Data from a randomized, double-blind, placebo-controlled clinical study of patients with PNH demonstrated that over a 26-week period, half of the participants receiving eculizumab experienced less hemolysis as well as stabilization of hemoglobin concentrations, and required fewer blood transfusions as compared to the placebo group. Eculizumab is well tolerated, although due to its blockade of the membrane attack complex there is an increased risk of meningococcal infection. Thus, all patients must receive meningococcal vaccination prior to starting eculizumab. Clinical studies demonstrate that eculizumab may be the first successful specific therapy for the treatment of PNH. (c) 2007 Prous Science. All rights reserved.