DAIICHI SANKYO Announces Enrollment in the Two Largest Single Phase III Trials so far for the Prevention of Stroke in AF

DAIICHI SANKYO announced today that the ongoing trials ENGAGE AF-TIMI 48 (The Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation) and HOKUSAI VTE with their investigational factor Xa inhibitor edoxaban are enrolling in accordance to plan. The projected recruitment of ENGAGE AF-TIMI 48 and HOKUSAI VTE are 20,500 and 7,500 patients, respectively. ENGAGE AF-TIMI 48 and HOKUSAI VTE are the two largest single phase III trials in atrial fibrillation (AF) and venous thromboembolism (VTE) to date.
It is estimated that throughout Europe 4.5 million people suffer from AF, and approximately 370,000 deaths are related to VTE per year in six major European countries (France, Germany, Italy, Spain, Sweden, and the UK). Due to the aging population, the number of patients with AF is likely to increase 2.5 fold by the year 2050.
The ENGAGE AF-TIMI 48 study is investigating the safety and efficacy of edoxaban in preventing strokes and systemic embolic events in patients with AF. ENGAGE AF-TIMI 48 is the only phase III trial in atrial fibrillation in which a factor Xa inhibitor is investigated at two different dose levels. The study was initiated in late 2008, and DAIICHI SANKYO expects the study to be concluded in 2012.
The HOKUSAI VTE study is evaluating the safety and efficacy of edoxaban in preventing recurrent venous thromboembolic events in patients with deep vein thrombosis (DVT) and/or pulmonary embolism (PE). The study was initiated in late 2009, and DAIICHI SANKYO expects the study to be concluded in 2012.
In addition to ENGAGE AF-TIMI 48 and HOKUSAI VTE, edoxaban has been investigated for the prevention of VTE after major orthopedic surgery in Japanese and Taiwanese patients in the STARS-E3 (Studying Thrombosis After Replacement Surgery) trial. The first, positive results of this phase III trial were presented in July of this year at the International Congress of Thrombosis (ICT) in Milan.

-ENGAGE AF-TIMI 48 Study Design
The ENGAGE AF-TIMI 48 study is investigating the safety and efficacy profile of two different doses of edoxaban versus warfarin in individuals with AF at moderate to high risk of stroke. Patients are randomized to one of three treatment groups: high dose regimen (edoxaban 60 mg once-daily), low dose regimen (edoxaban 30 mg once-daily), and warfarin. Approximately 20,500 patients will be enrolled making ENGAGE AF-TIMI 48 the largest stroke prevention study in AF with a novel anticoagulant so far, and the expected median treatment duration is 24 months. The primary efficacy endpoint is the composite clinical outcome of stroke and systemic embolic events; the primary safety endpoint is the incidence of major bleeding.

-HOKUSAI VTE Study Design
The HOKUSAI VTE trial is evaluating the safety and efficacy of edoxaban in the treatment and prevention of recurrent thromboembolic events in patients with deep-vein thrombosis and/or pulmonary embolism. Two different treatment groups will receive enoxaparin or unfractionated heparin for at least five and up to 12 days, followed by double-blind warfarin or edoxaban 60 mg once-daily. The primary efficacy endpoint is the composite clinical outcome of symptomatic recurrent DVT, non-fatal symptomatic recurrent PE, and fatal PE; the primary safety endpoint is the incidence of major and clinically relevant non-major bleeding. Patients will be treated for up to 12 months in accordance to the standard of care and international guidelines.