PB0532 - The Factor XIa Antibody Osocimab Combined with Enoxaparin Strongly Inhibits Clotting in Extracorporeal Circuits in vitro

Monday, June 26, 2023

18:30 – 19:30 ET

Room: Exhibition

Co-Author(s)

ES

Eslam Samaha

Specialist for Internal Medicine
Department of Clinical Pharmacology
Vienna, Wien, Austria

Presenting Author(s)

Katarina D. Kovacevic, PhD

Post Doc
Department of Clinical Pharmacology, Medical University of Vienna
Wien, Wien, Austria

Co-Author(s)

MS

Michael Schwameis

Doctor
Department of Clinical Pharmacology
Vienna, Wien, Austria
SS

Sabine Schranz

Coauthor
Department of Clinical Pharmacology, Medical University of Vienna
Vienna, Wien, Austria
BW

Bruno Watschinger

Specialist for Internal Medicine
Department of Internal Medicine III, Division of Nephrology, Center for Medical Physics and Biomedical Engineering,
Vienna, Wien, Austria
AB

Anja Buchmüller

Globar Program Manager
Bayer
Wuppertal, Bayern, Germany
MS

Martin Stoiber

Doctor
Medical Univeristy of Vienna
Vienna, Wien, Austria
BJ

Bernd Jilma

Specialist for Internal Medicine
department of Clinical Pharmacology
Vienna, Wien, Austria

Background: Effective antithrombotics that have little or no impact on hemostasis in extracorporeal blood circuits remain an unmet medical need. Targeted inhibition of activated factor XI could represent an attractive alternative to conventionally used enoxaparin.

Aims: We aim to show that in vitro anticoagulation achieved by additional FXIa-inhibition is superior to standard anticoagulation by low molecular weight heparin (LMWH) alone

Methods: This study compared the additional antithrombotic effect of a novel monoclonal antibody osocimab which is directed against FXIa to that of LMWH in three different in vitro models of extracorporeal blood circulation including devices used for hemodialysis, left ventricular support and extracorporeal membrane oxygenation. Whole blood donated by 34 healthy volunteers was spiked with enoxaparin or enoxaparin plus osocimab and then circulated for several hours in the extracorporeal circuits. The primary endpoint was time to filter clotting.

Results: Out of 40 subjects screened 34 (50% male, mean age 32 years (+/-9)) were enrolled in the study. Ten subjects were randomly assigned to the HD group, 12 to the ECMO group and 12 to the LVAD group. The addition of osocimab to enoxaparin significantly prolonged the time to filter clotting from 120min (IQR:105-150) to 180min (IQR:180-180) in HD circuits, from 127min (IQR:38-210) to 180min (IQR:69-240) in ECMO circuits and from 36min (IQR:18-59) to 113min (IQR:51-120) in LVAD circuits. Furthermore, it preserved fibrinogen levels (HD:227mg/dl vs. 170mg/dl; LVAD: 229 mg/dl vs. 50mg/dl; ECMO:229mg/dl vs. 170mg/dl), improved platelet aggregation in hemodialysis and LVAD devices but not ECMO, and prolonged clotting times in thromobelastometry during the procedures.

Conclusion(s): In aggressive ex vivo models of extracorporeal circuits due to the frequent re-circulation of blood and lack of endothelial cells, inhibition of FXIa by osocimab, when combined with enoxaparin, prolonged time to circuit clotting, providing support for further in vivo testing.