Safety and efficacy of the terminal complement inhibitor eculizumab in Japanese patients with paroxysmal nocturnal hemoglobinuria: the AEGIS Clinical Trial
- 12 January 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in International Journal of Hematology
- Vol. 93 (1), 36-46
- https://doi.org/10.1007/s12185-010-0748-9
Abstract
Paroxysmal nocturnal hemoglobinuria (PNH) is a progressive and life-threatening disease characterized by complement-mediated chronic hemolysis, resulting in serious life-threatening complications and early mortality. Eculizumab, a humanized anti-C5 monoclonal antibody that inhibits terminal complement activation, has been shown to reduce hemolysis in PNH patients. The pivotal open-label, 12-week phase II registration study (AEGIS) was designed to evaluate the efficacy and safety of eculizumab in Japanese patients with PNH. This trial achieved its primary endpoint of reducing intravascular hemolysis with high statistical significance. Twenty-seven of the 29 patients responded to eculizumab treatment, resulting in an 87% reduction in hemolysis (P < 0.0001) and subsequent improvement in anemia (P = 0.0003) despite reduction in transfusion requirements (P = 0.006). Fatigue and dyspnea significantly improved within 1–2 weeks of eculizumab treatment and the improvement was independent of changes in hemoglobin. Chronic kidney disease (CKD) was common (66%) and eculizumab treatment improved CKD in 41% of patients at 12 weeks (P < 0.001). Elevated thrombotic risk was evident in Japanese PNH patients and eculizumab treatment normalized d-dimer levels in 45% of patients with elevated d-dimers at baseline (P < 0.001). The AEGIS results demonstrate that eculizumab is effective, safe and well tolerated in Japanese patients with PNH.Keywords
This publication has 39 references indexed in Scilit:
- Long‐term effect of the complement inhibitor eculizumab on kidney function in patients with paroxysmal nocturnal hemoglobinuriaAmerican Journal of Hematology, 2010
- Effect of eculizumab on haemolysis‐associated nitric oxide depletion, dyspnoea, and measures of pulmonary hypertension in patients with paroxysmal nocturnal haemoglobinuriaBritish Journal of Haematology, 2010
- Evaluation of hemostasis and endothelial function in patients with paroxysmal nocturnal hemoglobinuria receiving eculizumabHaematologica, 2010
- Basal nitric oxide synthase activity is a major determinant of glomerular haemodynamics in humansJournal Of Hypertension, 2008
- Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuriaBlood, 2007
- Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuriaNature Biotechnology, 2007
- The role of nitric oxide in the regulation of glomerular haemodynamics in humansNephrology Dialysis Transplantation, 2004
- Fatigue in cancer patients compared with fatigue in the general United States populationCancer, 2002
- Inhibition of complement activity by humanized anti-C5 antibody and single-chain FvMolecular Immunology, 1996
- The European Organization for Research and Treatment of Cancer QLQ-C30: A Quality-of-Life Instrument for Use in International Clinical Trials in OncologyJNCI Journal of the National Cancer Institute, 1993