Abstract Number: PB0077
Meeting: ISTH 2021 Congress
Background: Factor XI (FXI) inhibition offers the promise of hemostasis-sparing anticoagulation for the prevention and treatment of arterial and venous thromboembolic events. Abelacimab is a novel fully human monoclonal antibody that targets the catalytic domain and has dual activity against the inactive zymogen Factor XI and the activated FXI.
Aims: To investigate the safety, pharmacokinetic (PK), and pharmacodynamic (PD) properties of single intravenous infusion and monthly subcutaneous administration of abelacimab in healthy volunteers and patients with atrial fibrillation, respectively.
Methods: In study ANT-003, healthy volunteers were administered single ascending doses of intravenous abelacimab (30 to 150 mg) or placebo. The ANT-003 study also included a cohort of obese but otherwise healthy subjects to evaluate the effect of body weight on PK properties. In study ANT-004, patients with atrial fibrillation were administered monthly subcutaneous doses of abelacimab (120 mg and 180 mg), or placebo, for 3 months. Key PK and PD parameters, including activated partial thromboplastin time (aPTT) and free FXI levels were assessed. These studies were approved by the local ethics committee and all volunteers provided written informed consent.
Results: Following intravenous administration of abelacimab, PK increased in an approximately dose-proportional manner. The mean terminal elimination half-life ranged from 25 to 30 days similar to that observed with subcutaneous dosing. Rapid dose- and time-dependent reductions from baseline in free FXI levels >99% were seen within an hour after intravenous infusion. Similarly, profound reductions in free FXI levels were maintained with subcutaneous monthly administration. Single intravenous infusion and multiple subcutaneous administration of abelacimab demonstrated a favorable safety profile with no major or clinically relevant non-major bleeding events.
Conclusions: The results provide a detailed profile of the PK and PD properties of abelacimab and support future clinical development of abelacimab as a once monthly anticoagulant.
To cite this abstract in AMA style:Yi BA, Freedholm D, Widener N, Wang X, Simard E, Galitz L, Al-Saady NM, Lepor NE, Lovern M, Bloomfield D. Pharmacokinetics and Pharmacodynamics of Abelacimab (MAA868), a Novel Dual Inhibitor of Factor XI and Factor XIa [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/pharmacokinetics-and-pharmacodynamics-of-abelacimab-maa868-a-novel-dual-inhibitor-of-factor-xi-and-factor-xia/. Accessed December 7, 2021.
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