Antithrombotic Effects of the Novel Small-Molecule Factor XIa Inhibitor Milvexian in a Rabbit Arteriovenous Shunt Model of Venous Thrombosis

Abstract Background  Factor XIa (FXIa) is an emerging therapeutic target, and FXIa inhibition is a promising mechanism to improve therapeutic index over current anticoagulants. Milvexian (BMS-986177/JNJ-70033093) is an oral small-molecule FXIa inhibitor. Objective  Milvexian's antithrombotic ef...

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Bibliographic Details
Published in:TH open : companion journal to thrombosis and haemostasis 2023-04, Vol.7 (2), p.e97-e104
Main Authors: Wang, Xinkang, Li, Qiu, Du, Fuyong, Shukla, Neetu, Nawrocki, Andrea R., Chintala, Madhu
Format: Article
Language:English
Subjects:
animal
anticoagulants
factor xi
Original
Original Article
pharmacology
thrombosis
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Summary:Abstract Background  Factor XIa (FXIa) is an emerging therapeutic target, and FXIa inhibition is a promising mechanism to improve therapeutic index over current anticoagulants. Milvexian (BMS-986177/JNJ-70033093) is an oral small-molecule FXIa inhibitor. Objective  Milvexian's antithrombotic efficacy was characterized in a rabbit arteriovenous (AV) shunt model of venous thrombosis and compared with the factor Xa inhibitor apixaban and the direct thrombin inhibitor dabigatran. Methods  The AV shunt model of thrombosis was conducted in anesthetized rabbits. Vehicle or drugs were administered as intravenous bolus plus a continuous infusion. Thrombus weight was the primary efficacy endpoint. Ex vivo activated partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin time (TT) were measured as the pharmacodynamic responses. Results  Milvexian dose dependently reduced thrombus weights by 34.3 ± 7.9, 51.6 ± 6.8 ( p  
ISSN:2512-9465
2567-3459
2512-9465
DOI:10.1055/a-2061-3311