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

Authors:
Austin G Kulasekararaj
Austin G Kulasekararaj
King's College London School of Medicine
United Kingdom
Anita Hill
Anita Hill
University of South Australia
Australia
Scott T Rottinghaus
Scott T Rottinghaus
Clinical Affairs
Saskia Langemeijer
Saskia Langemeijer
Molecular and Clinical Hematology Branch
United States
Richard Wells
Richard Wells
University of Waterloo
Anna Gaya
Anna Gaya
Institute of Hematoncology
Jong Wook Lee
Jong Wook Lee
Seoul St. Mary's Hospital
South Korea

Blood 2019 Feb 3;133(6):540-549. Epub 2018 Dec 3.

Bone Marrow Transplantation Unit, Saint Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.

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 ( < .0006 for all end points), including percentage change in LDH (difference, 9.21% [95% confidence interval (CI), -0.42 to 18.84], = .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 www.clinicaltrials.gov as #NCT03056040.

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Source
http://dx.doi.org/10.1182/blood-2018-09-876805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368201PMC

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February 2019
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References

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Farmakidis et al.
Neurol Clin 2018

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