Blood Journal
Leading the way in experimental and clinical research in hematology

Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria

  1. Robert A. Brodsky1,
  2. Neal S. Young2,
  3. Elisabetta Antonioli3,
  4. Antonio M. Risitano4,
  5. Hubert Schrezenmeier5,
  6. Jörg Schubert6,
  7. Anna Gaya7,
  8. Luke Coyle8,
  9. Carlos de Castro9,
  10. Chieh-Lin Fu10,
  11. Jaroslaw P. Maciejewski11,
  12. Monica Bessler12,
  13. Henk-André Kroon13,
  14. Russell P. Rother13, and
  15. Peter Hillmen14
  1. 1Johns Hopkins School of Medicine, Baltimore, MD;
  2. 2National Heart, Lung, and Blood Institute, Bethesda, MD;
  3. 3University of Florence, Florence, Italy;
  4. 4Federico II University of Naples, Naples, Italy;
  5. 5Institute of Transfusion Medicine, University Hospital Institute of Clinical Transfusion Medicine and Immunogenetics, Ulm; DRK-Blood Donor Service Baden-Württemberg-Hessen, Germany;
  6. 6Saarland University Medical School, Homburg-Saarland, Germany;
  7. 7Hospital Clinic of Barcelona, Institut d'Investigacions Biomedique Augist Pi i Sunyer (IDIBAPS), Barcelona, Spain;
  8. 8Royal North Shore Hospital, St Leonards, Australia;
  9. 9Duke University Medical Center, Durham, NC;
  10. 10Cleveland Clinic Florida, Weston, FL;
  11. 11Taussig Cancer Center, Cleveland Clinic, OH;
  12. 12Washington University in St Louis, MO;
  13. 13Alexion Pharmaceuticals, Cheshire, CT; and
  14. 14St James's Institute of Oncology, Leeds, United Kingdom


The terminal complement inhibitor eculizumab was recently shown to be effective and well tolerated in patients with paroxysmal nocturnal hemoglobinuria (PNH). Here, we extended these observations with results from an open-label, non–placebo-controlled, 52-week, phase 3 clinical safety and efficacy study evaluating eculizumab in a broader PNH patient population. Eculizumab was administered by intravenous infusion at 600 mg every 7 ± 2 days for 4 weeks; 900 mg 7 ± 2 days later; followed by 900 mg every 14 ± 2 days for a total treatment period of 52 weeks. Ninety-seven patients at 33 international sites were enrolled. Patients treated with eculizumab responded with an 87% reduction in hemolysis, as measured by lactate dehydrogenase levels (P < .001). Baseline fatigue scores in the FACIT-Fatigue instrument improved by 12.2 ± 1.1 points (P < .001). Eculizumab treatment led to an improvement in anemia. The increase in hemoglobin level occurred despite a reduction in transfusion requirements from a median of 8.0 units of packed red cells per patient before treatment to 0.0 units per patient during the study (P < .001). Overall, transfusions were reduced 52% from a mean of 12.3 to 5.9 units of packed red cells per patient. Forty-nine patients (51%) achieved transfusion independence for the entire 52-week period. Improvements in hemolysis, fatigue, and transfusion requirements with eculizumab were independent of baseline levels of hemolysis and degree of thrombocytopenia. Quality of life measures were also broadly improved with eculizumab treatment. This study demonstrates that the beneficial effects of eculizumab treatment in patients with PNH are applicable to a broader population of PNH patients than previously studied. This trial is registered at as NCT00130000.

  • Submitted June 6, 2007.
  • Accepted November 18, 2007.
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