ISTH Congress Abstracts

Official abstracts site for the ISTH Congress

MENU 
  • Home
  • Congress Archive
    • ISTH 2022 Congress
    • ISTH 2021 Congress
    • ISTH 2020 Congress
  • Resources
  • Search

Antithrombotic Effects of a Novel Small Molecular Fxia Inhibitor BMS-986177/JNJ-70033093 in a Rabbit AV-Shunt Model of Thrombosis

X. Wang, Q. Li, F. Du, N. Shukla, A. Nawrocki, M. Chintala

Janssen Research and Development, LLC, Spring House, United States

Abstract Number: PB0179

Meeting: ISTH 2020 Congress

Theme: Coagulation and Natural Anticoagulants » Coagulation Factors and Inhibitors

Background: FXIa inhibition is a promising drug target with the potential for an improved therapeutic index over the currently approved oral anticoagulants. BMS-986177/JNJ-70033093 (BMS-177/JNJ-3093) is a novel small molecular inhibitor of FXIa currently in Phase II clinical trials.

Aims: The current study characterized the antithrombotic efficacy of BMS-177/JNJ-3093 in a rabbit arterial-venous (AV)- shunt model of venous thrombosis and compared it to the FXa inhibitor apixaban and the direct thrombin inhibitor dabigatran.

Methods: The AV-shunt model of thrombosis was conducted in anesthetized rabbits where a shunt was placed between the femoral artery and femoral vein for 40 mins. A thread placed in the shunt served as the thrombogenic surface. Vehicle or drugs were administered as i.v. bolus plus infusion. Thrombus weights were served as the primary efficacy end-point. Blood was collected to measure activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), and drug levels.

Results: BMS-177/JNJ-3093 significantly reduced thrombus weight in the rabbit AV-shunt model of thrombosis, with 34.3 ± 7.9, 51.6 ± 6.8 (p< 0.01, n=5) and 66.9 ± 4.8 % (p< 0.001, n=6) inhibition vs. vehicle, respectively, at 0.52 + 0.06, 1.70 + 0.06 and 5.47 + 0.53 µM BMS-177/JNJ-3093 plasma levels, with 50% inhibition of thrombus weight (ED50) at 1.60 ± 0.05 µM. Ex vivo clotting data supported a dose-dependent prolongation of aPTT (with 1.54-, 2.23- and 3.12-fold increases respectively from the baseline), but no changes in PT and TT. Dose-dependent inhibition in thrombus weight was also demonstrated for both apixaban and dabigatran, with ED50 at 0.11 ± 0.02 µM and 0.20 ± 0.02 µM, respectively.

Conclusions: These results demonstrate that BMS-177/JNJ-3093 is an effective antithrombotic agent for the prevention of venous thrombosis supporting the clinical testing in a Phase II total knee arthroplasty study.

To cite this abstract in AMA style:

Wang X, Li Q, Du F, Shukla N, Nawrocki A, Chintala M. Antithrombotic Effects of a Novel Small Molecular Fxia Inhibitor BMS-986177/JNJ-70033093 in a Rabbit AV-Shunt Model of Thrombosis [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/antithrombotic-effects-of-a-novel-small-molecular-fxia-inhibitor-bms-986177-jnj-70033093-in-a-rabbit-av-shunt-model-of-thrombosis/. Accessed September 27, 2023.

« Back to ISTH 2020 Congress

ISTH Congress Abstracts - https://abstracts.isth.org/abstract/antithrombotic-effects-of-a-novel-small-molecular-fxia-inhibitor-bms-986177-jnj-70033093-in-a-rabbit-av-shunt-model-of-thrombosis/

Simple Search

Supported By:

Takeda logo

ISTH 2022 Congress site

Visit the official web site for the ISTH 2022 Virtual Congress »

  • Help & Support
  • About Us
  • Cookies & Privacy
  • Wiley Job Network
  • Terms & Conditions
  • Advertisers & Agents
Copyright © 2023 John Wiley & Sons, Inc. All Rights Reserved.
Wiley