Milvexian is an investigational oral anticoagulant designed to prevent blood clots. It represents a new class of agents being studied for managing conditions associated with abnormal clotting.
What Milvexian is Designed to Treat
Milvexian is currently being studied for its potential to prevent blood clots in several patient populations. A primary focus is on preventing secondary strokes in individuals who have recently experienced an ischemic stroke or a transient ischemic attack (TIA). These events occur when blood flow to the brain is blocked.
The drug is also under investigation for preventing strokes in patients diagnosed with atrial fibrillation, a common heart rhythm disorder that increases stroke risk due to clot formation in the heart. Additionally, milvexian is being evaluated for its ability to prevent venous thromboembolism, which includes deep vein thrombosis and pulmonary embolism, following major orthopedic surgeries such as knee replacement. Abnormal blood clots can lead to severe complications, including heart attacks or blockages in the lungs.
How Milvexian Works
Milvexian functions as a Factor XIa inhibitor, targeting a specific enzyme within the body’s complex blood clotting system. Blood coagulation involves a cascade of reactions where various factors are activated in sequence to form a clot. Factor XI (FXI) is an inactive protein that becomes activated to Factor XIa (FXIa) when a blood vessel is injured, often by enzymes like Factor XIIa or thrombin.
Once activated, Factor XIa plays a role in amplifying the production of thrombin, a central enzyme that converts fibrinogen into fibrin, forming the meshwork of a blood clot. Milvexian works by binding to and inhibiting Factor XIa, thereby interrupting this amplification process.
The scientific rationale is that Factor XIa contributes significantly to pathological clot formation while having a more limited role in hemostasis, the natural process of clotting that stops bleeding. This targeted inhibition aims to prevent unwanted clots without excessively interfering with the body’s ability to stop bleeding.
Clinical Trial Findings
Milvexian has progressed through various stages of clinical evaluation, including a series of Phase 2 studies known as the AXIOMATIC trials. The AXIOMATIC-TKR trial, focusing on patients undergoing total knee replacement surgery, demonstrated that milvexian reduced the risk of postoperative venous thromboembolism in a dose-dependent manner. This reduction in clot formation was observed without an increase in bleeding events when compared to enoxaparin, a standard anticoagulant.
Another Phase 2 study, AXIOMATIC-SSP, investigated milvexian for preventing secondary strokes after an ischemic stroke or transient ischemic attack. While this trial did not meet its primary objective, it showed a reduction in the relative risk of symptomatic ischemic stroke across most tested dosages compared to a placebo. These Phase 2 results suggested a positive antithrombotic profile and a favorable safety profile regarding bleeding.
Building on these findings, milvexian is now being evaluated in the large-scale Phase 3 LIBREXIA clinical program. This program involves nearly 50,000 patients across three parallel clinical trials: LIBREXIA STROKE, LIBREXIA ACS (Acute Coronary Syndrome), and LIBREXIA AF (Atrial Fibrillation). The LIBREXIA STROKE trial specifically assesses milvexian, often in combination with antiplatelet therapy, for preventing further strokes in patients who have experienced a recent ischemic stroke or TIA. These Phase 3 trials are designed to confirm the efficacy and safety of milvexian in broader patient populations.
Comparison to Current Anticoagulants
Milvexian is distinct from many currently available anticoagulants, particularly the direct oral anticoagulants (DOACs) like apixaban and rivaroxaban. Existing DOACs primarily work by inhibiting Factor Xa, an enzyme positioned further downstream in the coagulation cascade. Warfarin, another established anticoagulant, operates by interfering with different vitamin K-dependent clotting factors.
Milvexian, conversely, specifically inhibits Factor XIa, an enzyme located further upstream in the intrinsic pathway of blood coagulation. This difference in target is significant because Factor XI is thought to play a more prominent role in pathological clot formation while having a less pronounced role in the normal clotting process that stops bleeding from an injury.
Therefore, by targeting Factor XIa, milvexian is theorized to offer effective clot prevention with a potentially reduced risk of bleeding compared to existing anticoagulants. The ongoing Phase 3 LIBREXIA AF trial, for instance, directly compares milvexian to apixaban to evaluate its efficacy and safety profile for stroke prevention in atrial fibrillation.