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International Journal of Hematology

, Volume 93, Issue 1, pp 36–46 | Cite as

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

  • Yuzuru KanakuraEmail author
  • Kazuma Ohyashiki
  • Tsutomu Shichishima
  • Shinichiro Okamoto
  • Kiyoshi Ando
  • Haruhiko Ninomiya
  • Tatsuya Kawaguchi
  • Shinji Nakao
  • Hideki Nakakuma
  • Jun-ichi Nishimura
  • Taroh Kinoshita
  • Camille L. Bedrosian
  • Marye Ellen Valentine
  • Gus Khursigara
  • Keiya Ozawa
  • Mitsuhiro Omine
Original Article

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

Paroxysmal nocturnal hemoglobinuria Complement-inactivating agents Hemolysis Eculizumab Hematopoietic stem cell 

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Copyright information

© The Japanese Society of Hematology 2011

Authors and Affiliations

  • Yuzuru Kanakura
    • 1
    Email author
  • Kazuma Ohyashiki
    • 2
  • Tsutomu Shichishima
    • 3
  • Shinichiro Okamoto
    • 4
  • Kiyoshi Ando
    • 5
  • Haruhiko Ninomiya
    • 6
  • Tatsuya Kawaguchi
    • 7
  • Shinji Nakao
    • 8
  • Hideki Nakakuma
    • 9
  • Jun-ichi Nishimura
    • 1
  • Taroh Kinoshita
    • 10
  • Camille L. Bedrosian
    • 11
  • Marye Ellen Valentine
    • 11
  • Gus Khursigara
    • 11
  • Keiya Ozawa
    • 12
  • Mitsuhiro Omine
    • 13
  1. 1.Department of Hematology and OncologyOsaka University HospitalSuitaJapan
  2. 2.Tokyo Medical University HospitalTokyoJapan
  3. 3.Fukushima Medical UniversityFukushimaJapan
  4. 4.Division of HematologyKeio University School of MedicineTokyoJapan
  5. 5.Department of Hematology and OncologyTokai UniversityIseharaJapan
  6. 6.University of TsukubaTsukubaJapan
  7. 7.Kumamoto UniversityKumamotoJapan
  8. 8.Cellular Transplantation BiologyKanazawa UniversityKanazawaJapan
  9. 9.Department of Hematology/OncologyWakayama Medical UniversityWakayamaJapan
  10. 10.Research Institute for Microbial DiseasesOsaka University HospitalSuitaJapan
  11. 11.Alexion PharmaceuticalsCheshireUSA
  12. 12.Jichi Medical University HospitalTochigiJapan
  13. 13.Showa University Fujigaoka HospitalYokohamaJapan

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