Deep Vein Thrombosis

January 6, 2014

Daiichi Sankyo has released results of phase III trials of edoxaban for the treatment of either acute symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE) or both, in cancer and non-cancer patients. The global, event-driven, randomized, double-blind, parallel-group phase III study involved 8,292 patients in 439 clinical sites across 37 countries. Patients with either a history of cancer (n=563) or with active cancer (n=208) treated with the once-daily factor Xa-inhibitor edoxaban had a numerically lower incidence of recurrent symptomatic venous thromboembolism (VTE) compared to warfarin (3.7% v. 7.1%, respectively; hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.28 to 1.00). Once-daily edoxaban also had a lower incidence of clinically relevant bleeding (major or non-major) compared to warfarin in cancer patients (12.4% v. 18.8%, respectively; HR, 0.64; 95% CI, 0.45 to 0.92). In the subset of 208 patients with active cancer, once-daily edoxaban had a rate of VTE recurrence of 3.7% compared to 7.1% for warfarin (HR, 0.55; 95% CI, 0.16 to 1.85) and an incidence of clinically relevant bleeding of 18.3% compared to 25.3% for warfarin (HR, 0.72; 95% CI, 0.40 to 1.30).

September 23, 2013

Daiichi Sankyo released results of a phase III study of edoxaban in 8,292 patients with acute symptomatic deep vein thrombosis (DVT) and/or pulmonary embolism (PE). The global, event-driven, randomized, doubleblind, parallel-group study in 439 clinical sites across 37 countries gave both treatment groups open-label enoxaparin or unfractionated heparin for at least five days, and either warfarin or placebo (administered to edoxaban group), followed by double-blind edoxaban 60mg (n=4,118) (edoxaban 30mg for patients with renal impairment or low body weight or p-glycoprotein inhibitor use) or warfarin (n=4,122) for three months to one year. Edoxaban was dosed at 60mg oncedaily, 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 30mg. The reduced dose had an efficacy profile consistent with the overall study cohort, with fewer recurrent VTE events in patients receiving 30mg edoxaban (n=733) compared to warfarin (n=719) (VTE recurrence of 3% vs. 4.2%; HR, 0.73; 95% CI, 0.42 to 1.26). Clinically relevant bleeding in patients receiving edoxaban 30mg was significantly lower compared to warfarin (7.9% v. 12.8%, respectively) (HR, 0.62; 95% CI, 0.44 to 0.86). Among patients with DVT (n=4,921), VTE recurrence was similar in the edoxaban and warfarin groups (3.4% v. 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 lower for patients treated with once-daily edoxaban compared to warfarin (2.8% v. 3.9%, respectively) (HR, 0.73; 95% CI, 0.50 to 1.06). In a sub-group analysis, patients with severe PE and evidence of right ventricular dysfunction (defined as NT pro-BNP >/= 500pg/mL, n=938) treated with edoxaban had a 48% lower risk of recurrent symptomatic VTE compared to warfarin (3.3% v. 6.2%, respectively) (HR, 0.52; 95% CI, 0.28 to 0.98). Daiichi Sankyo plans to submit NDAs for edoxaban for VTE by the first quarter of 2014 in the U.S., Japan and Europe.