• Régis Peffault de Latour, Robert A Brodsky, Stephan Ortiz, Antonio M Risitano, Jun H Jang, Peter Hillmen, Alexander D Kulagin, Austin G Kulasekararaj, Scott T Rottinghaus, Rasha Aguzzi, Xiang Gao, Richard A Wells, and Jeff Szer.
• French Reference Center for Aplastic Anemia and PNH Hematology-Bone Marrow Transplantation, Hôpital Saint-Louis AP-HP, Paris, France.
• Br. J. Haematol. 2020 Nov 1; 191 (3): 476-485.

AbstractRavulizumab, a novel long-acting complement component 5 (C5) inhibitor administered every 8 weeks (q8w), was non-inferior to eculizumab for all efficacy outcomes in two randomised, open-label, phase 3 trials in C5 inhibitor-naïve (Study 301) and eculizumab-experienced (Study 302) adult patients with paroxysmal nocturnal haemoglobinuria (PNH). This pre-specified analysis characterised ravulizumab pharmacokinetics (PK), pharmacodynamics (PD; free C5 levels), and PD differences between medications (Study 301, n = 246; Study 302, n = 195). Ravulizumab PK parameters were determined using non-compartmental analysis. Serum free C5 was quantified with a Gyros-based fluorescence assay (ravulizumab) and an electrochemiluminescence ligand-binding assay (eculizumab). Ravulizumab PK parameters were numerically comparable in both studies; the median time to maximum concentrations ranged from 2·3 to 2·8 and 2·3 to 2·6 h in studies 301 and 302, respectively. Ravulizumab steady-state serum concentrations were achieved immediately after the first dose and sustained throughout treatment. For ravulizumab, the mean (SD) post hoc terminal elimination half-life was 49·7 (8·9) days. Serum free C5 concentrations <0·5 µg/ml were achieved after the first ravulizumab dose and sustained throughout treatment in both studies. In a minority of patients, free C5 concentrations <0·5 µg/ml were not consistently achieved with eculizumab in either study. Ravulizumab q8w was more consistent in providing immediate, complete, sustained C5 inhibition than eculizumab every-2-weeks in patients with PNH.© 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.

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