Journal article

Characterization of breakthrough hemolysis events observed in the phase III randomized studies of ravulizumab versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria

Robert A Brodsky, Regis Peffault de latour, Scott T Rottinghaus, Alexander Roeth, Antonio M Risitano, Ilene C Weitz, Peter Hillmen, Jaroslaw P Maciejewski, Jeff Szer, Jong Wook Lee, Austin G Kulasekararaj, Lori Volles, Andrew I Damokosh, Stephan Ortiz, Lori Shafner, Peng Liu, Anita Hillc, Hubert Schrezenmeier

HAEMATOLOGICA | FERRATA STORTI FOUNDATION | Published : 2021

Abstract

Eculizumab is first-line treatment for paroxysmal nocturnal hemoglobinuria (PNH); however, approximately 11%-27% of patients may experience breakthrough hemolysis (BTH) on approved doses of eculizumab. Ravulizumab, a new long-acting C5 inhibitor with a four-times longer mean half-life than eculizumab, provides immediate, complete, and sustained C5 inhibition over 8-week dosing intervals. In two phase 3 studies, ravulizumab was noninferior to eculizumab (Pinf ≤0.0004) for the BTH endpoint; fewer patients experienced BTH with ravulizumab versus eculizumab in both studies (301 [complement inhibitor-naive patients], 4.0% vs 10.7%; 302 [patients stabilized on eculizumab at baseline], 0% vs 5.1%)...

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