109 Systematic review on PK of emicizumab Population characteristics Eleven studies [18, 19, 27-34] provided original PK data of emicizumab in humans and yielded 607 subjects (Table 2) after excluding four studies [24, 35-37] with doublereported subjects. These 607 unique subjects were either volunteers (n = 140) or PwHA (n = 467). The PwHA included adults and adolescents (n = 328) and children younger than 12 years (n = 139). The PwHA with and without FVIII inhibitors were similarly represented across studies. Severe haemophilia A and the Asian and Caucasian races were predominant across the studies. Table 2. Population characteristics. Eleven studies providing original PK data on emicizumab in unique subjects. Total = 607 (n [%]) Population Volunteer 140 (23%) Haemophilia A 467 (77%) FVIII inhibitor 234 (39%) Age group Child with haemophilia A (<12 years) 139 (23%) Adult or adolescent (≥12 years) 468 (77%) Volunteer 140 (23%) Haemophilia A 328 (39%) Haemophilia A severity Severe 436 (75%) Moderate 6 (1%) Mild 5 (1%) Dose-concentration relationship The original PK data were used to investigate the dose−concentration relationship, therefore excluding two pharmacometric analysis studies (re-used data), two preliminary studies (shorter follow-up period than their consecutive studies) and a case report (no steady state conditions). The PK data from the PwHA (n = 469) demonstrated a linear dose−concentration relationship when the Ctrough,ss was plotted according to increasing doses of emicizumab per week (Figure 1). The longer dose intervals (Q2W and Q4W) were associated with a lower Ctrough,ss. 6
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