The Ministry of Health, Labour and Welfare in Japan approved dabigatran etexilate, Boehringer Ingelheim’s novel, oral direct thrombin inhibitor under the brand name Prazaxa for the prevention of ischemic stroke and systemic embolism in patients with non-valvular Atrial Fibrillation (AF) marking the first approval of a novel oral anticoagulant in the Asia-Pacific region and specifically Japan in nearly 50 years.

Prazaxa will be available to the approximately 830,000 AF patients at risk of stroke in Japan, with 150 mg bid (given as 2 capsules of 75 mg) recommended as the standard dose and 110 mg bid available for specific patient types considered to be at a higher risk of bleeding. The approval is based on findings from RE-LY, the largest AF trial completed to date. In RE-LY, dabigatran etexilate 150 mg bid significantly reduced the risk of stroke and systemic embolism by 35 percent beyond the reduction achieved with well controlled warfarin (median TTR 67%), the long-time standard of care, in addition to reductions in life-threatening and intracranial bleeding. Dabigatran etexilate is the only novel oral anticoagulant proven to be superior to warfarin and was recently approved in the US and Canada.

Dr Stuart Connolly, co-principal investigator of RE-LY, director, Division of Cardiology at McMaster University and member of The Population Health Research Institute, Hamilton, Ontario said, “Until today, physicians in Japan have had little choice but to use warfarin, which imposes challenging restrictions on people’s quality of life. Besides being a safe and more effective alternative to warfarin, dabigatran etexilate does not require monitoring, dose adjustments and is not affected by food, which truly is a huge shift in the treatment of stroke prevention in AF.”

The approval of Prazaxa is one of the fastest ever undertaken by the Japanese Ministry of Health, Labour and Welfare with authorisation of the novel agent gained 10 months after the filing of a new drug application. The speed of the approval underlines the current unmet need in stroke prevention in AF in Japan and the strength of data supporting dabigatran etexilate in this indication.

Professor Klaus Dugi, corporate senior vice president Medicine, Boehringer Ingelheim said, “The approval of dabigatran etexilate for stroke prevention in AF in Japan is a very important step towards our goal to make this treatment available to all patients with AF at risk of stroke. It is a milestone as it marks the first approval of a novel oral anticoagulant in the Asia-Pacific region in nearly 50 years. We look forward to working with regulatory authorities worldwide regarding the approval of this breakthrough therapy.”

Dabigatran etexilate is at the forefront of a new generation of oral anticoagulants/Direct Thrombin Inhibitors (DTIs) targeting a high unmet medical need in the prevention and treatment of acute and chronic thromboembolic diseases.

Potent antithrombotic effects are achieved with direct thrombin inhibitors by specifically blocking the activity of thrombin (both free and clot-bound), the central enzyme in the process responsible for clot (thrombus) formation. In contrast to vitamin-K antagonists, which variably act via different coagulation factors, dabigatran etexilate provides effective, predictable and consistent anticoagulation with a low potential for drug-drug interactions and no drug-food interactions, without the need for routine coagulation monitoring or dose adjustment.

Dabigatran etexilate has already been approved in 75 countries under the trademark Pradaxa (in Canada: Pradax) for the primary prevention of venous thromboembolic events (blood clots) in adults who have undergone elective total hip or elective total knee replacement surgery.

Boehringer Ingelheim’s clinical trial programme to evaluate the efficacy and safety of dabigatran etexilate encompasses studies in: primary prevention of Venous Thrombo-Embolism (VTE) in patients undergoing elective total hip and knee replacement surgeries, treatment of acute VTE, secondary prevention of VTE, secondary prevention of cardiac events in patients with Acute Coronary Syndrome (ACS), stroke prevention in Atrial Fibrillation (AF).

RE-LY (Randomized Evaluation of Long term anticoagulant therapY) was a global, phase III, randomised trial of 18,113 patients enrolled in over 900 centres in 44 countries, investigating whether dabigatran etexilate (2 blinded doses) is as effective as well controlled warfarin with target INR of 2.0-3.0 for stroke prevention. Patients were followed-up in the study for a median of 2 years with a minimum of 1 year follow-up.

The primary endpoint of the trial was incidence of stroke (including haemorrhagic) or systemic embolism. Secondary outcome measures included all-cause death, incidence of stroke (including haemorrhagic), systemic embolism, pulmonary embolism, acute myocardial infarction, and vascular death (including death from bleeding).

Compared to well controlled warfarin, dabigatran etexilate showed in the trial: significant reduction in the risk of stroke and systemic embolism – including haemorrhagic strokes with dabigatran etexilate 150 mg bid, Significantly lower major bleeding events with dabigatran etexilate 110 mg bid, significantly lower life threatening and intracranial bleeding with both doses and significant reduction in vascular mortality with dabigatran etexilate 150 mg bid.

AF is the most common heart rhythm condition, affecting nearly one in four people over the age of 40 and 1% of the total population, rising to 10% in people over the age of 80. People with AF are more likely to experience blood clots, which increases the risk of stroke by five-fold. Up to three million people worldwide suffer strokes related to AF each year, which are typically severe and disabling, with one half of this population dying within one year. Strokes due to AF tend to be severe, with an increased likelihood of death (20%), and disability (60%). Many AF-related strokes can be prevented with appropriate anti-thrombotic therapy.

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