Rationale for the Milvexian Dosing in the Phase 3 LIBREXIA Program.
Academic Article
Overview
abstract
BACKGROUND: Milvexian is an oral, small-molecule inhibitor of factor (F) XIa undergoing evaluation in Phase 3 clinical trials. OBJECTIVES: This manuscript aims to explain the rationale underpinning the hypothesis that FXIa may be a safer target for anticoagulants than FXa; describes the pharmacology of milvexian; reviews the results of the Phase 2 trials with milvexian, and details how the Phase 2 program informed the dosing regimens for the Phase 3 trials. METHODS: This narrative review addresses the above objectives with the primary focus on addressing how the milvexian dosing regimens were selected for the Phase 3 LIBREXIA program, which compares milvexian with apixaban in atrial fibrillation (AF) in the LIBREXIA AF trial (NCT05757869), and with placebo, in addition to background single or dual antiplatelet therapy, in acute coronary syndrome (ACS) in the LIBREXIA ACS trial (NCT05754957), and in non-cardioembolic ischemic stroke and high-risk transient ischemic attack in the LIBREXIA Stroke trial (NCT05702034). CONCLUSIONS: The milvexian dose regimen selected for the LIBREXIA AF trial is 100 mg twice daily, and for the LIBREXIA ACS and Stroke trials is 25 mg twice daily. The Phase 3 LIBREXIA program will determine whether these dose regimens afford safe and effective anticoagulation in approximately 50,000 patients with AF, ACS, or prior stroke.
