Abstract Number: PB0942
Meeting: ISTH 2020 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical
Background: Emicizumab, a recombinant, humanized, bispecific antibody, restores the function of missing activated factor (F)VIII in PwHA by bridging activated FIX and FX. It showed a favorable safety profile and clinically meaningful bleed prevention in PwHA with FVIII inhibitors in the STASEY study (NCT03191799; Jimenez-Yuste, et al. ISTH 2019).
Aims: To present the pharmacokinetics (PK) and pharmacodynamics (PD) of emicizumab prophylaxis in PwHA with FVIII inhibitors in STASEY.
Methods: Following informed consent and ethics committee approval, PwHA with FVIII inhibitors aged ≥12 years received 3 mg/kg once-weekly (QW) emicizumab for 4 weeks followed by 1.5 mg/kg QW maintenance dosing (data cut-off: 20 May 2019; N=193). PK and PD were assessed throughout emicizumab exposure (median 51 weeks). Emicizumab levels were measured with a validated ELISA assay. PD was assessed using a chromogenic FVIII activity assay (FVIII:C) containing human reagents, and activated partial thromboplastin time (aPTT). Changes from baseline in prothrombin time (PT/INR) and D-dimer were determined. FVIII inhibitor titers were measured using a chromogenic Bethesda assay containing bovine reagents.
Results: Mean steady-state emicizumab trough plasma concentrations reached >50 µg/mL by Week 5 and were sustained throughout emicizumab maintenance dosing, consistent with a half-life of ~30 days. PD markers demonstrated on-target activity of emicizumab. Mean reported FVIII:C activity increased to ~19 U/dL by Week 5 and was maintained throughout the study. Reported FVIII:C activity correlated with emicizumab concentration. aPTT was normalized after the first emicizumab dose and subsequently remained at or just below the normal range. Emicizumab did not affect concentrations of safety markers of activated coagulation (PT and D-dimer). Participants´ FVIII inhibitor titers remained stable or declined slightly over time.
Conclusions: The PK and PD profiles, and PK/PD relationship of emicizumab in STASEY were consistent with those from other emicizumab studies (Adamkewicz, et al. ISTH 2017; Kiialainen, et al. EAHAD 2019).
To cite this abstract in AMA style:
Kiialainen A, Petry C, Jimenez-Yuste V, Santagostino E, Ozelo M, Meier O, Robson S, Castaman G, Klamroth R, Schmitt C. Pharmacokinetics and Coagulation Biomarkers in Persons with Hemophilia A (PwHA) and FVIII Inhibitors Receiving Emicizumab in the Phase IIIb STASEY Study [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/pharmacokinetics-and-coagulation-biomarkers-in-persons-with-hemophilia-a-pwha-and-fviii-inhibitors-receiving-emicizumab-in-the-phase-iiib-stasey-study/. Accessed September 24, 2023.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/pharmacokinetics-and-coagulation-biomarkers-in-persons-with-hemophilia-a-pwha-and-fviii-inhibitors-receiving-emicizumab-in-the-phase-iiib-stasey-study/