Canadian co-led, global trial shows dabigatran etexilate as effective as well
controlled warfarin, with less bleeding, in treatment of acute venous
thromboembolism

Results from RE-COVER(TM) study published online in the New England Journal of Medicine(1)

BURLINGTON , ON, Dec. 6 /CNW/ - Results from the landmark RE-COVER(TM) study were presented today at the American Society of Hematology Annual Meeting and published online in the New England Journal of Medicine. The results showed dabigatran etexilate 150 mg twice-daily (BID) was equally as effective as well-controlled warfarin at preventing recurrent venous thromboembolism (VTE) (p(less than)0.001 for prespecified non-inferiority margin).(1) VTE refers to blood clots (thrombi) which originate in the veins, and includes deep vein thrombosis (DVT), which can lead to a potentially fatal acute complication pulmonary embolism (PE).

For safety, dabigatran etexilate demonstrated a significant 37 per cent reduction in major or clinically relevant non-major bleeding (p=0.002). Major bleeding was comparable between dabigatran etexilate and warfarin. For any bleeds, dabigatran etexilate showed a significant 29 per cent reduction (p=0.0002) compared to warfarin. These results were achieved without any evidence of liver toxicity.(1)

"The results of RE-COVER(TM) are a long-awaited breakthrough in the treatment of VTE; not only does dabigatran etexilate offer an effective therapy to prevent recurrent VTE, it does so with less bleeding than warfarin," commented Dr. Sam Schulman , Principle Investigator, Department of Medicine, McMaster University, Hamilton, Ontario. "Warfarin is a highly effective therapy when well-controlled within its narrow therapeutic range, as in clinical trials, but in the real world sufficient control is rarely achieved and maintained, leaving patients poorly protected from VTE or at-risk of bleeding. With dabigatran etexilate, we have a therapy that protects our patients effectively and safely, without need for frequent laboratory monitoring and dose changes."

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

Earlier this year, the RE-LY(R) study (18,113 patients in 44 countries worldwide) showed groundbreaking results for dabigatran etexilate convincingly beating warfarin in stroke prevention in atrial fibrillation.(2)

As such, dabigatran etexilate has the protential to benefit even more patients and replace warfarin as the treatment of choice.

In total, four trials involving 8,900 patients are exploring dabigatran etexilate in VTE treatment: RE-COVER(TM) and RE-COVER(TM) II in acute VTE and RE-MEDY(TM) and RE-SONATE(TM) in prevention of secondary VTE. The results of RE-COVER(TM) and the very favourable results of RE-LY(2) add to the growing database of evidence supporting the efficacy and safety of dabigatran etexilate across a wide range of acute and chronic thromboembolic disorders from the RE-VOLUTION(R) clinical development program involving over 38,000 patients.

About Venous Thromboembolism

Venous thromboembolism, which includes deep vein thrombosis, which can lead to a potentially fatal acute complication, pulmonary embolism, is the third most common cardiovascular disease worldwide (after coronary heart disease and stroke).(3) Every year, approximately 100,000 Canadians experience VTE and as many as 30,000 will die from acute PE.(4) VTE kills more Canadians each year than breast cancer, AIDS and car crashes combined.(5) For almost one-quarter of patients, PE can cause sudden dealth, so prevention is key.(6) Although many patients recover from DVT and PE without any problems, there are a number of long-term complications associated with VTE that can cause substantial illness.(7,8,9)

About RE-COVER(TM)(1)

RE-COVER(TM) is a global, phase III, randomized, double blind, parallel-group study evaluating whether oral dabigatran etexilate (150 mg BID) is as effective and safe (non-inferior to) warfarin (INR 2.0-3.0) for 6 months treatment of acute symptomatic venous thromboembolism, following initial treatment (5-11 days) with a parenteral anticoagulant. The study involved 2,539 patients, including 299 Canadian patients. The primary efficacy endpoint was composite of recurrent symptomatic VTE and deaths related to VTE. The secondary efficacy endpoints were: composite of recurrent symptomatic VTE and all deaths; symptomatic DVT; symptomatic PE; deaths related to VTE and; all deaths. Safety endpoints included: incidence of bleeding events; adverse events; vital signs, laboratory measures, especially liver function tests (LFT); and acute coronary syndrome (ACS).

About RE-VOLUTION(R)

RE-COVER(TM) is part of Boehringer Ingelheim's extensive RE-VOLUTION(R) clinical trial program - evaluating the efficacy and safety of dabigatran etexilate against current standard therapy in over 38,000 patients. Beyond RE-COVER(TM) the RE-VOLUTION(R) trial program encompasses studies in:

    
    -  Primary prevention of venous thromboembolism (VTE) - RE-NOVATE(R),
       RE-NOVATE(R) II, RE-MODEL(R) and RE-MOBILIZE(R)

    -  Treatment of venous thromboembolism (VTE) in RE-COVER(TM) II

    -  Prevention of stroke in atrial fibrillation (AF) - results of RE-LY(R)
       were presented at the ESC in August 2009

    -  Secondary prevention of ACS - results of the phase II RE-DEEM were
       presented at the AHA in November 2009

    -  Secondary prevention of VTE in the RE-MEDY(TM) and RE-SONATE(TM)
       trials
    

About dabigatran etexilate (PRADAX(TM))

Dabigatran etexilate is a new generation of oral anticoagulants - direct thrombin inhibitors (DTIs) - being investigated to target a high unmet medical need in the prevention and treatment of acute and chronic thromboembolic diseases. Dabigatran etexilate has been approved in Canada as PRADAX(TM) and is widely used in over 40 countries for the prevention of VTE in adults who have undergone elective total hip or elective total knee replacement surgery.

About Boehringer Ingelheim ( Canada ) Ltd.

The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany , it operates globally with 138 affiliates in 47 countries and 41,300 employees.

Founded in 1885, the family-owned company has been committed to researching and developing novel products of high therapeutic value for human and veterinary medicine. In 2008, Boehringer Ingelheim posted net sales of 11.6 billion euro while spending one fifth of net sales in its largest business segment Prescription Medicines on research and development.

The Canadian headquarters of Boehringer Ingelheim was established in 1972 and the Research and Development Centre located in Laval, Québec, Canada since 1988. Boehringer Ingelheim ( Canada ) Ltd. employs more 700 employees and more than 150 scientists across the country.

For more information please visit www.boehringer-ingelheim.ca.

References

    
      1. Schulman S, Kearon C, Kakkar AK, et al. Dabigatran etexilate versus
         warfarin in the treatment of acute venous thromboembolism. N Engl J
         Med 2009;361. Published online 6 December 2009
      2. Connolly S, Ezekowitz D, Yusuf S, et al. Dabigatran versus warfarin
         in patients with atrial fibrillation. N Eng J Med 2009;361:1139-51
      3. Hawkins D. The role of oral direct thrombin inhibitors in the
         prophylaxis of venous thromboembolism. Pharmacotherapy
         2004;24:179S-183S
      4. Bloxom C, Bristow L (November 3, 2009). Sunnybrook Recognized as
         Leader on Blood Clot Prevention. Press Release. http://www.marketwire.com/press-release/Sunnybrook-Health-Sciences-Centre-1070099.html. Retrieved December 4, 2009.
      5. Getting started kit: Venous thromboembolism prevention how-to guide.
         2008 Canadian Patient Safety Institute, pg. 6
      6. Heit JA. Venous thromboembolism: disease burden, outcomes and risk
         factors. J Thromb Haemost. 2005;3:1611-17
      7. Kahn SR, Ginsberg JS. The post-thrombotic syndrome: current
         knowledge, controversies, and directions for future research. Blood
         Rev 2002;16:155-65
      8. Pengo V, Lensing A, Prins M et al. Incidence of chronic
         thromboembolic pulmonary hypertension after pulmonary embolism. NEJM
         2004;350:2257-64
      9. Hansson PO, Sorbo J, Eriksson H. Recurrent venous thromboembolism
         after deep vein thrombosis: incidence and risk factors. Arch Intern
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For further information: Jeanelle Frampton, Environics Communications, [phone], [email protected]