Edoxaban, an investigative once-daily oral factor Xa inhibitor to arrest blood clotting, has been submitted for approval in Japan by Daiichi Sankyo.
Daiichi Sankyo has submitted a New Drug Application to the Ministry of Health, Labor and Welfare in Japan seeking approval of the anticoagulant, edoxaban, for the prevention of venous thromboembolism (VTE) after major orthopedic surgery, the company announced.
Edoxaban is an oral anticoagulant that directly and specifically inhibits Factor Xa, a clotting factor in the blood.
Like the antiplatelet agent Prasugrel, it is designed for the treatment of thromboembolic diseases. While antiplatelet agents work on diseases associated with arterial thrombosis, in particular on cerebral and myocardial infarctions, the Factor Xa inhibitor Edoxaban is expected to offer an effective therapy for venous thrombosis.
A venous thrombosis is a blood clot resulting from the slowing down of the blood flow, e.g. the so-called Economy Class Syndrome, a thrombosis caused by poor blood circulation in the veins of the legs when the legs are kept angled in a seating position for a long duration. Clots may travel through the bloodstream to the lungs and block the pulmonary vessels, resulting in the severe impairment of pulmonary functions (pulmonary thromboembolism triggered by deep vein thrombosis).
Blood clots formed through stagnation of the blood flow due to cardiac arrhythmias may travel by way of the blood circulation to the brain and block the cerebral vessels, resulting in cerebral embolism (thromboembolism triggered by atrial fibrillation).
Results from pivotal Phase III studies showed that once-daily oral administration of edoxaban reduced the incidence of venous thromboembolism in patients undergoing total knee replacement or total hip replacement, and the non-inferiority to injectable enoxaparin sodium was confirmed.
“Upon approval, we believe that edoxaban, with its simple once-daily oral dosing, will be a significant improvement for patients undergoing orthopedic surgery in Japan,” stated Dr. Kazunori Hirokawa, head of the R&D Division of Daiichi Sankyo, Co., Ltd.
The pivotal Phase III studies were randomized, double-blind, parallel group, multi-center trials comparing a once-daily, 30 mg oral dose of edoxaban to 2,000 IU (20 mg) twice-daily subcutaneous injections of enoxaparin sodium. Treatment was provided for 11 to 14 days in both trials.
The primary efficacy endpoint in both trials was to confirm non-inferiority of edoxaban to enoxaparin sodium for the prevention of asymptomatic and symptomatic deep vein thrombosis and symptomatic pulmonary embolism.
The primary safety endpoint in both trials was to compare the incidence of major and clinically relevant non-major bleeding between edoxaban and enoxaparin sodium groups.
Daiichi has been studying edoxaban for several indications, including the prevention of stroke and systemic embolic events in patients with atrial fibrillation, as well as the acute treatment and long-term secondary prevention of deep vein thrombosis.
In ENGAGE AF-TIMI 48 once-daily edoxaban is being tested against warfarin in more than 16,500 patients with atrial fibrillation for the prevention of stroke and systemic embolic events. ENGAGE AF-TIMI 48 began enrollment in late 2008.
HOKUSAI VTE is the largest single trial for the secondary prevention of recurrent VTE in patients with deep vein thrombosis and pulmonary embolism as well as for the acute treatment of VTE to date. VTE began enrollment in early 2010.
Both HOKUSAI VTE and ENGAGE AF-TIMI 48 are Phase III, multi-national, randomized, double-blind studies.
Daiichi Sankyo Group has a portfolio of marketed pharmaceuticals for hypertension, hyperlipidemia, and bacterial infections.
The Group is engaged in the development of treatments for thrombotic disorders and focused on the discovery of novel oncology and cardiovascular-metabolic therapies.