Emicizumab assay evaluations and results from an Australian field study of emicizumab measurement

Abstract

Emicizumab is a recombinant, humanised bispecific antibody which acts as a FVIII mimetic and is a therapeutic option for haemophilia A. Plasma emicizumab levels may sometimes be required. Multiple one-stage clotting assays (OSA) and one human component chromogenic assay (CSA) were used to measure emicizumab both centrally and by a field study. The study samples drug concentrations range included within therapy range of 35-70 μg/mL. All assays were modified from traditional FVIII assays to enable replacement of plasma calibrators with emicizumab calibrators. Central laboratory OSA mean recovery levels (target) for six spike levels of emicizumab were close to target at 120.5 (120), 81.6 (80), 40.9 (40), 21.4 (20), 10.7 (10) and 5.5 (5) μg/mL. Field study OSA mean recoveries were similarly close to target. Between method coefficients of variation were <9% in both the central laboratory and field study assays, except for the 5 μg/mL sample which was 12.3%. CSA mean recoveries were within 10% of target at 80, 50 and 20 μg/mL levels. This study affirms that emicizumab can be measured by OSA using many types of activated partial thromboplastin time (APTT) reagents and is also measurable by the human CSA. The assays showed good precision, accuracy and linearity both locally and in a field study setting.

Keywords: Haemophilia A; assay; automation; bi-specific antibody; emicizumab.