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

Austin G. Kulasekararaj, Anita Hill, Scott T. Rottinghaus, Saskia Langemeijer, Richard Wells, F. Ataulfo Gonzalez-Fernandez, Anna Gaya, Jong Wook Lee, Emilio Ojeda Gutierrez, Caroline I. Piatek, Jeff Szer, Antonio Risitano, Shinji Nakao, Eric Bachman, Lori Shafner, Andrew I. Damokosh, Stephan Ortiz, Alexander Röth and Regis Peffault de Latour

Key Points

  • Ravulizumab every 8 weeks is noninferior to eculizumab every 2 weeks across all efficacy end points in eculizumab-experienced PNH patients.

  • Patients with PNH may be safely and effectively switched from labeled-dose eculizumab every 2 weeks to ravulizumab every 8 weeks.

There is a Blood Commentary on this article in this issue.


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 (Pinf < .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.

  • Submitted September 26, 2018.
  • Accepted November 18, 2018.
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