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

Fingerprint

Complement Inactivating Agents
Paroxysmal Hemoglobinuria
Clinical Trials
Safety
Hemolysis
Chronic Renal Insufficiency
Complement Activation
Therapeutics
eculizumab
Dyspnea
Fatigue
Anemia
Hemoglobins

Keywords

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

ASJC Scopus subject areas

  • Hematology

Cite this

Safety and efficacy of the terminal complement inhibitor eculizumab in Japanese patients with paroxysmal nocturnal hemoglobinuria : The AEGIS Clinical Trial. / Kanakura, Yuzuru; Ohyashiki, Kazuma; Shichishima, Tsutomu; Okamoto, Shinichiro; Ando, Kiyoshi; Ninomiya, Haruhiko; Kawaguchi, Tatsuya; Nakao, Shinji; Nakakuma, Hideki; Nishimura, Jun Ichi; Kinoshita, Taroh; Bedrosian, Camille L.; Valentine, Marye Ellen; Khursigara, Gus; Ozawa, Keiya; Omine, Mitsuhiro.

In: International Journal of Hematology, Vol. 93, No. 1, 01.2011, p. 36-46.

Research output: Contribution to journalArticle

Kanakura, Y, Ohyashiki, K, Shichishima, T, Okamoto, S, Ando, K, Ninomiya, H, Kawaguchi, T, Nakao, S, Nakakuma, H, Nishimura, JI, Kinoshita, T, Bedrosian, CL, Valentine, ME, 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, vol. 93, no. 1, pp. 36-46. https://doi.org/10.1007/s12185-010-0748-9
Kanakura, Yuzuru ; Ohyashiki, Kazuma ; Shichishima, Tsutomu ; Okamoto, Shinichiro ; Ando, Kiyoshi ; Ninomiya, Haruhiko ; Kawaguchi, Tatsuya ; Nakao, Shinji ; Nakakuma, Hideki ; Nishimura, Jun Ichi ; Kinoshita, Taroh ; Bedrosian, Camille L. ; Valentine, Marye Ellen ; Khursigara, Gus ; Ozawa, Keiya ; Omine, Mitsuhiro. / Safety and efficacy of the terminal complement inhibitor eculizumab in Japanese patients with paroxysmal nocturnal hemoglobinuria : The AEGIS Clinical Trial. In: International Journal of Hematology. 2011 ; Vol. 93, No. 1. pp. 36-46.
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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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AU - Ohyashiki, Kazuma

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AU - Okamoto, Shinichiro

AU - Ando, Kiyoshi

AU - Ninomiya, Haruhiko

AU - Kawaguchi, Tatsuya

AU - Nakao, Shinji

AU - Nakakuma, Hideki

AU - Nishimura, Jun Ichi

AU - Kinoshita, Taroh

AU - Bedrosian, Camille L.

AU - Valentine, Marye Ellen

AU - Khursigara, Gus

AU - Ozawa, Keiya

AU - Omine, Mitsuhiro

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