A pharmacokinetic and pharmacodynamic evaluation of asundexian: a novel factor XIa inhibitor for stroke prevention

Expert Opin Drug Metab Toxicol. 2024 Nov-Dec;20(11-12):1003-1011. doi: 10.1080/17425255.2024.2402496. Epub 2024 Oct 7.

Abstract

Introduction: Antithrombotic therapy is the mainstay of ischemic stroke prevention. Current drugs (antiplatelets and oral anticoagulants) lead to increased bleeding risks, and the rates of stroke recurrence, despite antithrombotic therapy, are still elevated. There is a need for novel antithrombotic therapies with superior effectiveness but without increased bleeding risk. Factor XIa inhibitors might cover this gap.

Areas covered: This manuscript examines the pharmacokinetic and pharmacodynamic properties of asundexian and the current clinical evidence regarding its application in preventing ischemic stroke.

Expert opinion: Asundexian shows a very favoring pharmacokinetic profile. Despite asundexian being inferior to apixaban for cardioembolic ischemic stroke, it could be useful in patients with non-cardioembolic ischemic stroke. Although antiplatelet therapy is the recommended treatment to prevent non-cardioembolic ischemic stroke, adding an anticoagulant might have beneficial effects through the dual-pathway inhibition strategy. Due to the potential risk of hemorrhagic transformation, there is hesitation to administer anticoagulants early to patients who have recently had an ischemic stroke, especially if they are also on antiplatelet therapy. However, clinical trials on asundexian confirmed its safety for bleeding, even when used with antiplatelets. A phase 3 trial is currently investigating the efficacy of asundexian in preventing non-cardioembolic ischemic stroke.

Keywords: Asundexian; absorption; bleeding; distribution; elimination; ischemic stroke; metabolism.

Publication types

  • Review
  • Comparative Study

MeSH terms

  • Animals
  • Anticoagulants* / administration & dosage
  • Anticoagulants* / adverse effects
  • Anticoagulants* / pharmacokinetics
  • Anticoagulants* / pharmacology
  • Benzamides
  • Factor XIa* / antagonists & inhibitors
  • Fibrinolytic Agents* / administration & dosage
  • Fibrinolytic Agents* / adverse effects
  • Fibrinolytic Agents* / pharmacokinetics
  • Fibrinolytic Agents* / pharmacology
  • Hemorrhage* / chemically induced
  • Humans
  • Hydrocarbons, Fluorinated
  • Ischemic Stroke* / prevention & control
  • Platelet Aggregation Inhibitors* / administration & dosage
  • Platelet Aggregation Inhibitors* / adverse effects
  • Platelet Aggregation Inhibitors* / pharmacokinetics
  • Platelet Aggregation Inhibitors* / pharmacology
  • Pyrazoles / administration & dosage
  • Pyrazoles / adverse effects
  • Pyrazoles / pharmacokinetics
  • Pyrazoles / pharmacology
  • Pyridones / administration & dosage
  • Pyridones / adverse effects
  • Pyridones / pharmacokinetics
  • Pyridones / pharmacology
  • Stroke / prevention & control
  • Triazoles

Substances

  • Anticoagulants
  • Platelet Aggregation Inhibitors
  • Factor XIa
  • Fibrinolytic Agents
  • apixaban
  • Pyridones
  • Pyrazoles
  • asundexian
  • Benzamides
  • Hydrocarbons, Fluorinated
  • Triazoles