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Blood. 2019 Feb 7;133(6):540-549. doi: 10.1182/blood-2018-09-876805. Epub 2018 Dec 3.

Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study.

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Department of Haematological Medicine, King's College Hospital, National Institute of Health Research/Wellcome King's Clinical Research Facility, London, United Kingdom.
Department of Haematology, Leeds Teaching Hospitals, Leeds, United Kingdom.
Alexion Pharmaceuticals, Inc., Boston, MA.
Radboudumc, Nijmegen, The Netherlands.
Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Hospital Clinico Universitario San Carlos, Department of Hematology, The Clínic Institute of Haematological and Oncological Diseases, Madrid, Spain.
Hospital Clínic de Barcelona, Barcelona, Spain.
Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain.
Jane Anne Nohl Division of Hematology, Keck School of Medicine of USC, Los Angeles, CA.
Clinical Haematology, Royal Melbourne Hospital, Melbourne, VIC, Australia.
Hematology, Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
Haematology/Respiratory Medicine, Faculty of Medicine, Institute of Medical Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.
Department of Hematology, West German Cancer Center, University Hospital Essen, Essen, Germany.
Bone Marrow Transplantation Unit, Saint Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
French Reference Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria, Saint Louis Hospital and University Paris Diderot, Paris, France; and.
Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation, Leiden, The Netherlands.


Ravulizumab, a new complement component C5 inhibitor administered every 8 weeks, was noninferior to eculizumab administered every 2 weeks in complement-inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria (PNH). This study assessed noninferiority of ravulizumab to eculizumab in clinically stable PNH patients during previous eculizumab therapy. In this phase 3, open-label, multicenter study, 195 PNH patients on labeled-dose (900 mg every 2 weeks) eculizumab for >6 months were randomly assigned 1:1 to switch to ravulizumab (n = 97) or continue eculizumab (n = 98). Primary efficacy end point was percentage change in lactate dehydrogenase (LDH) from baseline to day 183. Key secondary end points included proportion of patients with breakthrough hemolysis, change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score, transfusion avoidance, and stabilized hemoglobin. In 191 patients completing 183 days of treatment, ravulizumab was noninferior to eculizumab (P inf < .0006 for all end points), including percentage change in LDH (difference, 9.21% [95% confidence interval (CI), -0.42 to 18.84], P = .058 for superiority), breakthrough hemolysis (difference, 5.1 [95% CI, -8.89 to 18.99]), change in FACIT-Fatigue score (difference, 1.47 [95% CI, -0.21 to 3.15]), transfusion avoidance (difference, 5.5 [95% CI, -4.27 to 15.68]), and stabilized hemoglobin (difference, 1.4 [95% CI, -10.41 to 13.31]). The most frequently reported adverse event was headache (26.8%, ravulizumab; 17.3%, eculizumab). No meningococcal infections or discontinuations due to adverse events occurred. Patients with PNH may be safely and effectively switched from labeled-dose eculizumab administered every 2 weeks to ravulizumab administered every 8 weeks. This trial was funded by Alexion Pharmaceuticals, Inc., and is registered at as #NCT03056040.

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