Anouk Donners

110 Chapter 6 Figure 1. Linear dose−concentration relationship of emicizumab in PwHA. The mean or median Ctrough,ss according to increasing doses of emicizumab per week (mg/kg/week). Intervals Q2W and Q4W shown per week. Data from PwHA (n = 469) receiving multiple doses regimens were included (see ‘a’ for 15 study subgroups in Supplemental Table ST2). The PK data from the volunteers (n = 112) in the single-dose injection studies with increasing doses (0.1, 0.3 and 1 mg/kg), demonstrated constant primary PK parameters and a dose-linear increase in the exposure metrics Cmax and AUCinf, with an exponential decay over time. These PK parameters obtained per study subgroup are presented in Supplemental Figure SF2 and Supplemental Table ST1 and were similar across ethnicities. The study size weighted variability (%CV) of the Ctrough,ss was similar across FVIII inhibitor status (present or absent) and the various dosing intervals (QW, Q2W or Q4W), whereas children had slightly less variability than adults and adolescents (Figure 2). The overall weighted %CV of the Ctrough,ss in PwHA was 32% and ranged from 17% to 44% (Supplemental Table ST2).