TY  - JOUR
AU  - de Latour, RP
AU  - Brodsky, RA
AU  - Ortiz, S
AU  - Risitano, AM
AU  - Jang, JH
AU  - Hillmen, P
AU  - Kulagin, AD
AU  - Kulasekararaj, AG
AU  - Rottinghaus, ST
AU  - Aguzzi, R
AU  - Gao, X
AU  - Wells, RA
AU  - Szer, J
Y2  - 2020/11/27
Y1  - 2020/05/24
SN  - 0007-1048
UR  - http://hdl.handle.net/11343/252421
AB  - Ravulizumab, 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.
LA  - English
PB  - WILEY
T1  - Pharmacokinetic and pharmacodynamic effects of ravulizumab and eculizumab on complement component 5 in adults with paroxysmal nocturnal haemoglobinuria: results of two phase 3 randomised, multicentre studies
DO  - 10.1111/bjh.16711
IS  - British Journal of Haematology
VL  - 191
IS  - 3
SP  - 476-485
L1  - /bitstream/handle/11343/252421/bjh.16711.pdf?sequence=1&isAllowed=y
ER  -