Daiichi’s Edoxaban Beats Warfarin Targets

Daiichi Sankyo Co. Ltd. has posted results from a Phase III trial of its investigational, oral, once-daily direct factor Xa-inhibitor edoxaban. The compound met the primary efficacy endpoint of non-inferiority compared to warfarin for the prevention of stroke or systemic embolic events (SEE) in patients with non-valvular atrial fibrillation (NVAF). Once-daily edoxaban also demonstrated significant reductions in major bleeding compared to warfarin, achieving superiority for the principal safety endpoint. Results from the trial were presented at the American Heart Association (AHA) Scientific Sessions 2013 in Dallas and published online in the New England Journal of Medicine.

The trial compared two edoxaban treatment arms, 60 mg and 30 mg, with warfarin in 21,105 patients with NVAF for a median of 2.8 years. This represents the largest and longest trial with a novel anticoagulant in patients with atrial fibrillation performed to date. The edoxaban 60 mg treatment arm had an annual incidence of stroke or SEE of 1.18% versus 1.50% for warfarin, and significantly reduced major bleeding by 20%. The edoxaban 30 mg treatment arm had an annual incidence of stroke or SEE of 1.61% versus 1.50% for warfarin, and significantly reduced major bleeding by 53%.

In both edoxaban treatment arms, the edoxaban dose was halved for patients with clinical factors that were known to increase the risk of bleeding: renal impairment, low body weight or concomitant use of certain P-glycoprotein inhibitors. Patients receiving a reduced edoxaban dose in the 60 mg treatment arm had an annual incidence of stroke or SEE of 2.32% versus 2.68% for warfarin and a significantly reduced major bleeding incidence of 3.05% versus 4.85%. Patients receiving a reduced edoxaban dose in the 30 mg treatment arm had an annual incidence of stroke or SEE of 3.14% versus 2.68% for warfarin and a significantly reduced major bleeding incidence of 1.50% versus 4.85%

The company plans to submit NDAs for edoxaban in stroke prevention in atrial fibrillation and treatment of acute venous thromboembolism by 1Q14 in the U.S., Japan and Europe.