COMPARISON OF THE EFFECTS OF ABELACIMAB, ASUNDEXIAN, AND MILVEXIAN ON MEDICAL DEVICE-INDUCED CLOTTING AND THROMBIN GENERATION IN VITRO.

BACKGROUND: Medical devices, such as central venous catheters and mechanical heart valves (MHVs), are associated with an increased risk of thrombosis. Clotting on these devices is initiated via the contact system. Adsorbed factor (F) XII undergoes autoactivation and activates FXI, which then propagates coagulation. Abelacimab, asundexian, and milvexian are FXI or FXIa inhibitors that are currently undergoing or have completed Phase 3 evaluation. AIM: To compare the effects of abelacimab, asundexian, and milvexian on the activated partial thromboplastin time (aPTT), catheter-induced clotting, and device-induced thrombin generation. METHODS: The effects of abelacimab, asundexian, and milvexian on the aPTT (measured with the APTT-SP reagent), catheter segment-induced clotting, and thrombin generation induced by catheter segments or MHV leaflets were assessed in human platelet-poor plasma. Thrombin generation was monitored over time using a fluorogenic substrate, and peak thrombin and endogenous thrombin potential were quantified. RESULTS: Abelacimab, asundexian, and milvexian prolonged the aPTT and the catheter-induced clotting time and attenuated device-induced thrombin generation in a concentration-dependent manner. At clinically relevant concentrations, abelacimab and milvexian had more pronounced effects on aPTT, catheter-induced clotting, and device-induced thrombin generation than asundexian. Even at the highest concentration tested, asundexian produced less inhibition of device-induced thrombin generation than the other inhibitors. CONCLUSION: At concentrations achieved with the dosing regimens used in the Phase 3 trials, abelacimab and milvexian had greater effects on the aPTT, catheter-induced clotting, and thrombin generation induced by catheters or MHVs than asundexian did.