Novel oral anticoagulants: focus on the direct factor Xa inhibitor darexaban

Abstract

Introduction: Inhibition of the pathways of anticoagulation is widely used for the prevention and treatment of arterial and venous thrombosis. Vitamin K antagonists (VKAs) have been the mainstay of oral anticoagulation for more than 60 years. Their safety and effectiveness have been established in multiple clinical trials, for a variety of clinical indications. However, there are several limitations to the use of VKAs including delayed onset of action and dosage titration, numerous food and drug interactions and need for regular laboratory monitoring. To overcome some of the limitations of traditional agents, new oral anticoagulants (OACs) have been developed and evaluated.

Areas covered: In the present review article, the pharmacokinetic properties of darexaban are presented, along with the available preliminary clinical data. The performance of darexaban in respect to safety and efficacy compared with its competitors is further discussed.

Expert opinion: Darexaban is a potent direct factor Xa inhibitor that demonstrated impressive pharmacokinetic properties in pre-clinical studies. It was further successfully evaluated in the ONYX program for the prevention of venous thromboembolism in patients undergoing hip replacement. Finally, in the Phase II RUBY-1 trial, darexaban was tested on the top of standard antiplatelet therapy for the prevention of ischemic events in acute coronary syndrome (ACS) patients. Despite the fact that darexaban had a relatively uneventful clinical evaluation program, its further development was recently discontinued. This decision could probably reflect the non-favorite results in commercially attractive indications, such as secondary prevention post-ACS and the increased competition for less common or short-term indications such stroke prevention in AF or VTE prophylaxis respectively.

Keywords::

• clinical development
• darexaban
• factor Xa inhibitors
• oral anticoagulants
• YM150