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

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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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Author information

Authors and Affiliations

  1. Department of Hematology and Oncology, Osaka University Hospital, Suita, Japan

    Yuzuru Kanakura & Jun-ichi Nishimura

  2. Tokyo Medical University Hospital, Tokyo, Japan

    Kazuma Ohyashiki

  3. Fukushima Medical University, Fukushima, Japan

    Tsutomu Shichishima

  4. Division of Hematology, Keio University School of Medicine, Tokyo, Japan

    Shinichiro Okamoto

  5. Department of Hematology and Oncology, Tokai University, Isehara, Japan

    Kiyoshi Ando

  6. University of Tsukuba, Tsukuba, Japan

    Haruhiko Ninomiya

  7. Kumamoto University, Kumamoto, Japan

    Tatsuya Kawaguchi

  8. Cellular Transplantation Biology, Kanazawa University, Kanazawa, Japan

    Shinji Nakao

  9. Department of Hematology/Oncology, Wakayama Medical University, Wakayama, Japan

    Hideki Nakakuma

  10. Research Institute for Microbial Diseases, Osaka University Hospital, Suita, Japan

    Taroh Kinoshita

  11. Alexion Pharmaceuticals, Cheshire, CT, USA

    Camille L. Bedrosian, Marye Ellen Valentine & Gus Khursigara

  12. Jichi Medical University Hospital, Tochigi, Japan

    Keiya Ozawa

  13. Showa University Fujigaoka Hospital, Yokohama, Japan

    Mitsuhiro Omine

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  1. Yuzuru Kanakura
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Correspondence to Yuzuru Kanakura.

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Kanakura, Y., Ohyashiki, K., Shichishima, T. et al. Safety and efficacy of the terminal complement inhibitor eculizumab in Japanese patients with paroxysmal nocturnal hemoglobinuria: the AEGIS Clinical Trial. Int J Hematol 93, 36–46 (2011). https://doi.org/10.1007/s12185-010-0748-9

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  • DOI: https://doi.org/10.1007/s12185-010-0748-9

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