International Journal of Hematology

DOI: 10.1007/s12185-010-0748-9 Pages: 36-46

Safety and efficacy of the terminal complement inhibitor eculizumab in Japanese patients with paroxysmal nocturnal hemoglobinuria: the AEGIS Clinical Trial

1. Osaka University Hospital, Department of Hematology and Oncology

2. Tokyo Medical University Hospital

3. Fukushima Medical University

4. Keio University School of Medicine, Division of Hematology

5. Tokai University, Department of Hematology and Oncology

6. University of Tsukuba

7. Kumamoto University

8. Kanazawa University, Cellular Transplantation Biology

9. Wakayama Medical University, Department of Hematology/Oncology

10. Osaka University Hospital, Research Institute for Microbial Diseases

11. Alexion Pharmaceuticals

12. Jichi Medical University Hospital

13. Showa University Fujigaoka Hospital

Correspondence to:
Yuzuru Kanakura
Email: kanakura@bldon.med.osaka-u.ac.jp

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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.

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