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Long-term efficacy and safety of eculizumab in Japanese patients with PNH: AEGIS trial

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Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, progressive hematopoietic stem cell disorder characterized by chronic complement-mediated hemolysis leading to life-threatening complications and early mortality. Eculizumab, a humanized anti-C5 monoclonal antibody, inhibits terminal complement activation, reduces hemolysis, decreases the risk of thrombosis, and improves renal function and quality of life in PNH patients. The long-term efficacy and safety of eculizumab in Japanese patients were assessed in a 2-year extension to a 12-week, open-label study (AEGIS). Eculizumab treatment led to an immediate and sustained reduction in intravascular hemolysis (P < 0.001) and red blood cell transfusions (P = 0.0016) compared with baseline levels. There were no reports of thromboembolism during eculizumab treatment. The majority of patients had stable (56 %) or improved (41 %) renal function and an improved quality of life (P = 0.015), with sustained reductions in fatigue and dyspnea. Eculizumab was well tolerated; no deaths or serious hemolytic events were reported, and the rate of infections declined over time. There were no significant differences in the response to eculizumab in patients with or without bone marrow dysfunction. These results demonstrate that eculizumab is an effective, well-tolerated long-term treatment for Japanese PNH patients and leads to continued amelioration of some hemolytic complications.

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Acknowledgments

The authors would like to thank Gus Khursigara, PhD, for providing insightful comments on the manuscript; Masakazu Hase, PhD, for assistance with coordinating the manuscript preparation; and Mark Hughes, PhD, and Joshua Safran of Infusion Communications for writing and editorial support, which was funded by Alexion Pharmaceuticals.

Conflict of interest

YK has received research funding and been a consultant and board member for Alexion Pharmaceuticals. H. Ninomiya has received honoraria for lectures from Alexion Pharmaceuticals. T. Kawaguchi has received honoraria for lectures from Alexion Pharmaceuticals and works for an institution that has received research funding from Alexion Pharmaceuticals. SN works for an institution that has received research support from Alexion Pharmaceuticals. H. Nakakuma has received honoraria for lectures from Alexion Pharmaceuticals. J-IN has received research grants from and been a consultant and board member for Alexion Pharmaceuticals. T. Kinoshita has received honoraria for lectures from Alexion Pharmaceuticals. CLB is an employee of and owns stock in Alexion Pharmaceuticals. MO has received consulting fees/honoraria, travel support, and payments for development of educational presentations from Alexion Pharmaceuticals. K. Ohyashiki, TS, SO, KA, and K. Ozama have no conflicts of interest to declare.

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Authors and Affiliations

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

    Yuzuru Kanakura

  2. Tokyo Medical University, Tokyo, Japan

    Kazuma Ohyashiki

  3. Department of Cardiology and Hematology, School of Medicine, Fukushima Medical University, Fukushima, Japan

    Tsutomu Shichishima

  4. Division of Hematology, Department of Internal Medicine, Keio University Hospital, Tokyo, Japan

    Shinichiro Okamoto

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

    Kiyoshi Ando

  6. Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan

    Haruhiko Ninomiya

  7. Second Department of Internal Medicine, Kumamoto University School of Medicine, Kumamoto, Japan

    Tatsuya Kawaguchi

  8. Department of Hematology and Oncology, Kanazawa University Hospital, Kanazawa, Japan

    Shinji Nakao

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

    Hideki Nakakuma

  10. Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, Suita, Japan

    Jun-ichi Nishimura

  11. Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, Suita, Japan

    Taroh Kinoshita

  12. Alexion Pharmaceuticals, Cambridge, MA, USA

    Camille L. Bedrosian

  13. Division of Hematology, Jichi Medical University, Shimotsuke, Tochigi, Japan

    Keiya Ozawa

  14. Division of Hematology, 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. Long-term efficacy and safety of eculizumab in Japanese patients with PNH: AEGIS trial. Int J Hematol 98, 406–416 (2013). https://doi.org/10.1007/s12185-013-1404-y

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  • DOI: https://doi.org/10.1007/s12185-013-1404-y

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