Daiichi Sankyo’s Once-Daily Edoxaban Shows Comparable Efficacy and Superiority for the Principal Safety Endpoint Compared to Warfarin in a Phase 3 Study for the Treatment of Symptomatic VTE and Prevention of its Recurrence

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Updated: September 2, 2013

TOKYO, Sept. 2, 2013 — Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) today announced results from the global phase 3 Hokusai-VTE study of 8,292 patients with either acute symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE), or both. The study found that the investigational, oral, once-daily direct factor Xa-inhibitor edoxaban met the primary efficacy endpoint of non-inferiority compared to warfarin, following initial use of heparin in both arms, for the treatment and prevention of recurrent symptomatic venous thromboembolism (VTE). Once-daily edoxaban also demonstrated superiority compared to warfarin for the principal safety outcome of clinically relevant bleeding (the composite of major or clinically relevant non-major bleeding).(1) Results from Hokusai-VTE were presented today at the ESC Congress 2013 in Amsterdam and published online in the New England Journal of Medicine.

The Hokusai-VTE study was designed to reflect clinical practice using a flexible treatment duration of three to 12 months, including initial heparin treatment, in a broad spectrum of VTE patients, including those with severe PE. For the primary efficacy outcome, edoxaban demonstrated non-inferiority with a numerically lower incidence of recurrent symptomatic VTE compared to warfarin (3.2% vs. 3.5%, respectively) (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.70 to 1.13; P<0.001 for non-inferiority).(1) Edoxaban was also found to be superior to warfarin for the pre-specified principal safety outcome of clinically relevant bleeding (8.5% vs. 10.3%, respectively) (HR, 0.81; 95% CI, 0.71 to 0.94; P=0.004 for superiority).(1)

In the Hokusai-VTE study, patient specific dosing was applied according to the study protocol. Edoxaban was dosed at 60 mg once-daily, except for those patients with clinical factors that commonly impact response to oral anticoagulants (renal impairment, low body weight, or concomitant use of certain p-glycoprotein inhibitors) who received edoxaban 30 mg according to the study protocol. The reduced dose of edoxaban was found to have an efficacy profile consistent with the overall study cohort, with fewer recurrent VTE events in patients receiving 30 mg edoxaban (n=733) compared to warfarin (n=719) (VTE recurrence of 3.0% vs. 4.2%; HR, 0.73; 95% CI, 0.42 to 1.26). Clinically relevant bleeding in patients receiving edoxaban 30 mg was significantly lower compared to warfarin (7.9% vs. 12.8%, respectively) (HR, 0.62; 95% CI, 0.44 to 0.86).(1)

Among patients with DVT (n=4,921), VTE recurrence was similar in the edoxaban and warfarin groups (3.4% vs. 3.3%, respectively) (HR, 1.02; 95% CI, 0.75 to 1.38), while the incidence of recurrent VTE among patients with PE (n=3,319) was numerically lower for patients treated with once-daily edoxaban compared to warfarin (2.8% vs. 3.9%, respectively) (HR, 0.73; 95% CI, 0.50 to 1.06). Additionally, in a sub-group analysis, patients with severe PE and evidence of right ventricular dysfunction (defined as NT pro-BNP >/= 500 pg/mL, n=938) treated with edoxaban had a 48% lower risk of recurrent symptomatic VTE compared to warfarin (3.3% vs. 6.2%, respectively) (HR, 0.52; 95% CI, 0.28 to 0.98). (1)

“Hokusai-VTE was designed to include a broad range of VTE patients, including those with severe pulmonary embolism, and we are therefore pleased that the study found that edoxaban administered once-daily is as efficacious as warfarin for the prevention of recurrent symptomatic VTE while significantly reducing the risk of bleeding,” said Harry Buller, MD, PhD, Professor of Internal Medicine, Chairman of the Department of Vascular Medicine at the Academic Medical Center in Amsterdam, The Netherlands and Chairman of the Hokusai-VTE steering committee. “A promising finding was the sizeable reduction in recurrent symptomatic VTE among patients with severe pulmonary embolism who were treated with edoxaban.”

“We are excited about the results from the Hokusai-VTE study demonstrating that once-daily edoxaban may provide a new treatment option for a broad range of VTE patients. Daiichi Sankyo plans to submit New Drug Applications for edoxaban for VTE by the first quarter of 2014 in the U.S., Japan and Europe,” said Glenn Gormley, MD, PhD, Global Head of Research and Development and Senior Executive Officer, Daiichi Sankyo. “Daiichi Sankyo is committed to continuing the global development of edoxaban and looks forward to the presentation of the results from the phase 3 ENGAGE AF-TIMI 48 study in patients with atrial fibrillation at the 2013 American Heart Association Scientific Sessions in November.”

Original Source:: Daiichi Sankyo’s Once-Daily Edoxaban Shows Comparable Efficacy and Superiority for the Principal Safety Endpoint Compared to Warfarin in a Phase 3 Study for the Treatment of Symptomatic VTE and Prevention of its Recurrence