FDA approves edoxaban for reducing stroke risk

The FDA followed the advice of its advisory panel and added another novel oral anticoagulant to its approved drug list.

The FDA approved edoxaban (Savaysa, Daiichi Sanko) to reduce the risk of stroke in patients with nonvalvular atrial fibrillation. Edoxaban is a factor Xa-inhibitor. The drug joins three other approved novel oral anticoagulants approved for this indication—Bayer/Johnson & Johnson’s rivaroxaban (Xarelto), Boehringer Ingelheim’s dabigatran (Pradaxa), and Bristol-Myers Squibb’s  apixiban (Eliquis). Dabigatran is a direct thrombin inhibitor while all the other options are factor Xa inhibitors.

The FDA also approved edoxaban for the treatment of deep vein thrombosis and pulmonary embolism after five to 10 days of initial therapy with a parenteral anticoagulant.

On Oct. 30, 2014, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 9-1 in favor of approval for edoxaban. The panel reviewed results from the ENGAGE-AF TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) trial, which randomized patients with atrial fibrillation to receive warfarin a dose of either 30 mg or 60 mg edoxaban.

An intention-to-treat analysis favored the higher dose of edoxaban. The safety endpoint showed an annualized rate of major bleeding was 3.43 percent with warfarin, 2.75 percent with high-dose edoxaban and 1.61 percent with low-dose edoxaban. Cardiovascular death rates were 3.17 percent for warfarin, 2.74 percent for high-dose edoxaban and 2.71 percent for low-dose edoxaban.

A subgroup analysis based on renal function provoked discussion during the panel’s review. The U.S. label will state that edoxaban should not be prescribed to patients with nonvalvular atrial fibrillation and creatinine clearance levels greater than 95 mL/min, according to Daiichi Sanko, “because in that population there is an increased risk of ischemic stroke compared to warfarin.”

Daiichi Sanko plans to make the drug available in the U.S. in February.

Candace Stuart, Contributor

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