Milvexian: A Focus on a New Oral Anticoagulant that Targets Factor XIa for Thromboembolism Prophylaxis

Drugs that target factor XI and/or XIa have been evaluated as alternatives to existing anticoagulants, in light of studies that indicate that a decrease in Factor XI/XIa levels or activity may result in a lower risk of thrombosis without a significant increase in bleeding risk. Milvexian is an investigational small-molecule factor XIa inhibitor that has recently completed phase 2 clinical trials. Preclinical studies were suggestive of its potential to prevent arterial and venous thrombosis. It was well-tolerated in healthy participants, as well as in participants with mild or moderate hepatic impairment and moderate or severe renal impairment. Notably, patients who received milvexian after knee arthroplasty had a dose-proportional lower incidence of venous thromboembolism compared to patients who received postoperative enoxaparin, and they had a lower incidence of clinically relevant bleeding. A separate phase 2 trial was conducted that assessed the use of milvexian for secondary stroke prevention in patients who had ischemic stroke or transient ischemic attack. It failed its primary objective of establishing a dose-response relationship between milvexian and a composite endpoint of symptomatic ischemic stroke or covert brain infarction. The trial did, however, show a reduction in the relative risk of symptomatic ischemic stroke across most of the treatment groups receiving various dosages of milvexian compared to placebo. The efficacy of milvexian in secondary stroke prevention will be further assessed in an upcoming phase 3 trial. Additional upcoming phase 3 trials will also assess its efficacy in stroke prevention in patients with atrial fibrillation as well as in event reduction in patients with acute coronary syndrome.