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

Yuzuru Kanakura, 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

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)36-46
Number of pages11
JournalInternational journal of hematology
Volume93
Issue number1
DOIs
Publication statusPublished - 2011 Jan 1

Keywords

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

ASJC Scopus subject areas

  • Hematology

Fingerprint Dive into the research topics of 'Safety and efficacy of the terminal complement inhibitor eculizumab in Japanese patients with paroxysmal nocturnal hemoglobinuria: The AEGIS Clinical Trial'. Together they form a unique fingerprint.

  • Cite this

    Kanakura, Y., Ohyashiki, K., Shichishima, T., Okamoto, S., Ando, K., Ninomiya, H., Kawaguchi, T., Nakao, S., Nakakuma, H., Nishimura, J. I., Kinoshita, T., Bedrosian, C. L., Valentine, M. E., Khursigara, G., Ozawa, K., & Omine, M. (2011). Safety and efficacy of the terminal complement inhibitor eculizumab in Japanese patients with paroxysmal nocturnal hemoglobinuria: The AEGIS Clinical Trial. International journal of hematology, 93(1), 36-46. https://doi.org/10.1007/s12185-010-0748-9