2. Academic Validation
  3. News at XI: Moving Beyond Factor Xa Inhibitors

News at XI: Moving Beyond Factor Xa Inhibitors

  • J Thromb Haemost. 2023 Apr 26;S1538-7836(23)00343-4. doi: 10.1016/j.jtha.2023.04.021.
James C Fredenburgh 1,  Jeffrey I Weitz 2
Affiliations

Affiliations

  • 1 Department of Medicine, McMaster University, Hamilton, ON, Canada; Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada.
  • 2 Department of Medicine, McMaster University, Hamilton, ON, Canada; Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada. Electronic address: [email protected].
PMID: 37116752 DOI: 10.1016/j.jtha.2023.04.021
Abstract

Oral anticoagulants are a mainstay for the prevention and treatment of arterial and venous thrombosis. Direct oral anticoagulants (DOACs) have replaced vitamin K antagonists (VKAs) for many indications. Currently available DOACs include dabigatran, which inhibits Thrombin, and apixaban, edoxaban, and rivaroxaban, which inhibit factor (F) Xa. A new class of DOACs is under development. These new DOACs, which include asundexian and milvexian, inhibit FXIa, which is positioned in the intrinsic pathway of coagulation. Anticoagulants that target FXIa have the potential to be safer than the current DOACs because there is emerging evidence that FXI is essential for thrombosis but mostly dispensable for hemostasis. In addition to the oral inhibitors of FXIa, parenteral inhibitors also are under development. These include fesomersen, an antisense oligonucleotide that reduces the hepatic synthesis of FXI, abelacimab, an antibody that binds FXI and blocks its activation, and osocimab, an FXIa inhibitory antibody. Focusing on these new agents, this paper (a) describes the unmet needs in oral anticoagulation therapy, (b) explains why FXI is a promising target for new oral anticoagulants, (c) reviews the phase 2 clinical data with the new agents and describes the ongoing phase 3 trials, and (d) provides perspective on the opportunities and challenges for FXI inhibitors.

Keywords

anticoagulant; coagulation; factor XI; thromboembolism; thrombosis.

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