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Blood, 15 February 2008, Vol. 111, No. 4, pp. 1840-1847.
Prepublished online as a Blood First Edition Paper on November 30, 2007; DOI 10.1182/blood-2007-06-094136.
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CLINICAL TRIALS AND OBSERVATIONS
Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria
Robert A. Brodsky1,
Neal S. Young2,
Elisabetta Antonioli3,
Antonio M. Risitano4,
Hubert Schrezenmeier5,
Jörg Schubert6,
Anna Gaya7,
Luke Coyle8,
Carlos de Castro9,
Chieh-Lin Fu10,
Jaroslaw P. Maciejewski11,
Monica Bessler12,
Henk-André Kroon13,
Russell P. Rother13, and
Peter Hillmen14
1 Johns Hopkins School of Medicine, Baltimore, MD;
2 National Heart, Lung, and Blood Institute, Bethesda, MD;
3 University of Florence, Florence, Italy;
4 Federico II University of Naples, Naples, Italy;
5 Institute of Transfusion Medicine, University Hospital Institute of Clinical Transfusion Medicine and Immunogenetics, Ulm; DRK-Blood Donor Service Baden-Württemberg-Hessen, Germany;
6 Saarland University Medical School, Homburg-Saarland, Germany;
7 Hospital Clinic of Barcelona, Institut d'Investigacions Biomedique Augist Pi i Sunyer (IDIBAPS), Barcelona, Spain;
8 Royal North Shore Hospital, St Leonards, Australia;
9 Duke University Medical Center, Durham, NC;
10 Cleveland Clinic Florida, Weston, FL;
11 Taussig Cancer Center, Cleveland Clinic, OH;
12 Washington University in St Louis, MO;
13 Alexion Pharmaceuticals, Cheshire, CT; and
14 St 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 http://clinicaltrials.gov as NCT00130000
[ClinicalTrials.gov]
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