title: Safety and efficacy of the terminal complement inhibitor eculizumab in Japanese patients with paroxysmal nocturnal hemoglobinuria: the AEGIS clinical trial.
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.
authors.affiliation: Department of Hematology and Oncology, Osaka University Hospital, Suita, Japan. kanakura@bldon.med.osaka-u.ac.jp
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Kanakura
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ohyashiki
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Shichishima
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Okamoto
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ando
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Ninomiya
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakao
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakakuma
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Nishimura
authors.forename: Taroh
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Camille L
authors.initials: CL
authors.lastname: Bedrosian
authors.forename: Marye Ellen
authors.initials: ME
authors.lastname: Valentine
authors.forename: Gus
authors.initials: G
authors.lastname: Khursigara
authors.forename: Keiya
authors.initials: K
authors.lastname: Ozawa
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Omine
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D044466:Asian People; D003167:Complement Activation / Q000187:drug effects; D003182:Complement C5 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood / Q000188:drug therapy*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000139:chemically induced
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003182:Complement C5; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; C481642:eculizumab