Milvexian is an investigational oral anticoagulant developed through a collaboration between Janssen and Bristol Myers Squibb. This novel drug aims to prevent and treat blood clots. Its development seeks to improve existing anticoagulant therapies by offering a more favorable balance between preventing clots and minimizing bleeding risks.
How Milvexian Works
Milvexian targets and inhibits Factor XIa (FXIa), an enzyme in the coagulation cascade leading to blood clot formation. FXIa acts as an amplifier within the coagulation process, contributing to clot growth and stability. By blocking FXIa, milvexian disrupts this amplification, preventing blood clots.
This mechanism differs from many current anticoagulants, which target other factors like Factor Xa or thrombin. The underlying idea is that FXIa plays a more significant role in pathological clot formation (thrombosis) than in the normal process of stopping bleeding (hemostasis). This selective inhibition could reduce bleeding complications, a concern with existing blood thinners.
Conditions Milvexian Aims to Treat
Milvexian is currently under investigation for its potential to prevent and treat several major thrombotic conditions. A primary focus is stroke prevention in patients with atrial fibrillation, where irregular heartbeats can lead to clot formation in the heart, increasing stroke risk. Preventing clots is important for these patients to mitigate ischemic stroke, which occurs when a blood clot blocks blood flow to the brain.
Another application is preventing venous thromboembolism (VTE) in patients undergoing orthopedic surgery. These surgeries, especially total knee replacement, carry a high risk of VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE). Milvexian is also studied for patients with acute coronary syndrome (ACS), conditions involving sudden reduced blood flow to the heart, where clot prevention is crucial to avert heart attacks.
Clinical Trial Progress and Findings
Milvexian showed promising Phase 2 results. The AXIOMATIC-TKR study, involving 1,242 total knee replacement patients, evaluated milvexian’s efficacy in preventing VTE compared to enoxaparin. This study found milvexian reduced VTE risk dose-dependently without increasing bleeding across a wide range of doses (25 mg to 400 mg daily). The overall incidence of VTE with twice-daily milvexian was 12.2%, lower than a prespecified benchmark of 30% for patients without thromboprophylaxis.
AXIOMATIC-SSP investigated milvexian with antiplatelet therapy for patients who experienced an acute non-cardioembolic ischemic stroke or transient ischemic attack. Results indicated an approximate 30% relative risk reduction in recurrent ischemic strokes in several milvexian arms compared to placebo. This reduction was observed without an increase in severe bleeding events, such as symptomatic intracranial hemorrhage, even with patients on dual antiplatelet therapy.
These findings led to the Phase 3 LIBREXIA program, which enrolls nearly 50,000 patients across three trials: LIBREXIA STROKE, LIBREXIA ACS, and LIBREXIA AF. These trials evaluate milvexian’s efficacy and safety for its target indications. All three LIBREXIA indications received Fast Track Designation from the U.S. Food and Drug Administration (FDA), intended to expedite development and review for drugs addressing serious conditions with unmet medical needs.
Milvexian’s Place in Treatment
Milvexian offers a different approach to anticoagulation therapy. Existing direct oral anticoagulants (DOACs) like Factor Xa inhibitors are effective but carry a bleeding risk. Milvexian’s selective FXIa inhibition suggests an improved safety profile with reduced bleeding.
This characteristic could make milvexian useful for patients at high risk for both clotting and bleeding, or those who cannot tolerate current anticoagulants due to bleeding concerns. If proven effective with a favorable bleeding profile in Phase 3 trials, milvexian could provide an alternative for patients with atrial fibrillation, acute coronary syndrome, or those undergoing orthopedic surgery. Preventing thrombotic events with less bleeding could expand the number of patients who can safely receive anticoagulant treatment.
The Path Ahead for Milvexian
The Phase 3 LIBREXIA clinical trial program is ongoing. This program includes LIBREXIA STROKE, LIBREXIA ACS, and LIBREXIA AF, which are actively enrolling patients. These trials gather data on milvexian’s efficacy and safety in preventing stroke, managing acute coronary syndromes, and preventing VTE.
Estimated completion dates for these trials are in the coming years, with final data expected to inform regulatory submissions. If results demonstrate a superior benefit-risk profile, milvexian could gain regulatory approval and become available. Its introduction would represent a new class of oral anticoagulants, improving outcomes for many individuals at risk of thrombotic events.