The factor XIa antibody osocimab strongly inhibits clotting in extracorporeal circuits with human blood and in baboons.

BACKGROUND

Effective anticoagulant approaches in extracorporeal circuits with little impact on hemostasis are still an unmet medical need. Targeted inhibition of activated factor (F)XI might represent an attractive alternative or addition to conventional anticoagulation.

OBJECTIVES

We aimed to evaluate the additional antithrombotic effect of the monoclonal anti-FXIa antibody osocimab in in vitro and in vivo models of extracorporeal circulation.

METHODS

This study compared the additional antithrombotic effect of a novel monoclonal antibody, osocimab (anti-FXIa), with that of low-molecular-weight heparin in 3 models of extracorporeal blood circulation (hemodialysis [HD], left ventricular assist devices [LVADs], and extracorporeal membrane oxygenation [ECMO]). Whole blood donated by healthy volunteers was spiked with enoxaparin ± osocimab and circulated for several hours in extracorporeal circuits. The primary endpoint was time to filter clotting. Furthermore, we performed ECMO perfusion studies in baboons using unfractionated heparin and osocimab.

RESULTS

Of 40 subjects screened, 34 (50% male; mean age, 32 years [±9 SD]) were enrolled in the study. The addition of osocimab significantly prolonged the time to filter clotting from 120 minutes (IQR, 105-150) to 180 minutes (IQR, 180-180; = 10) in HD circuits, from 127 minutes (IQR, 38-210) to 180 minutes (IQR, 69-240; = 12) in ECMO circuits, and from 36 minutes (IQR, 18-59) to 113 minutes (IQR, 51-120; = 12) in LVAD circuits. Furthermore, it preserved fibrinogen concentrations (HD: 227 mg/dL vs 170 mg/dL; LVADs: 229 mg/dL vs 50 mg/dL; ECMO: 221 mg/dL vs 170 mg/dL) and platelet aggregation and prolonged clotting times in thromboelastometry. In baboons, osocimab significantly reduced the oxygenator's platelet deposition and terminal fibrin content.

CONCLUSION

Osocimab effectively inhibited clotting due to extracorporeal circulation.