Boehringer IngelheimBoehringer Ingelheim announces new milestones for the novel oral anticoagulant Pradaxa® (dabigatran etexilate) with over two million patient-years of experience in all licensed indications globally.(1) In addition, the company confirms research currently underway for Pradaxa® in new cardiovascular patient populations, as well as robust plans to gather real-world evidence in patients with non-valvular atrial fibrillation (NVAF). These plans are the cornerstone of an initiative to expand the scientific knowledge of stroke prevention and interventional cardiology with Pradaxa®, and demonstrate Boehringer Ingelheim's leadership and commitment to innovative solutions for patients and healthcare providers.

Initiating new research will help strengthen understanding of the safety and efficacy profile of Pradaxa®, the longest studied novel oral anticoagulant (NOAC). Since its discovery 20 years ago, Pradaxa® has been evaluated through the extensive RE-VOLUTION® clinical trial programme, which includes 10 clinical trials involving more than 40,000 patients in over 100 countries globally.(2-12)

"We are building upon Pradaxa®'s strong foundation in clinical research and prescribing experience to deepen our understanding of the treatment's benefit/risk profile to address evolving patient needs and benefit the cardiovascular community as a whole," commented Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. "Now, we are in discussions regarding plans for important new clinical trials where we see unmet patient need. Details of these plans will be announced in the near future."

The efficacy and safety of Pradaxa® to reduce risk of stroke and systemic embolism in patients with NVAF was established in the pivotal RE-LY® trial, one of the largest stroke prevention clinical studies ever conducted with NVAF patients.(9,10) To date, Pradaxa® has also been studied in the following areas:

  • Prevention of venous thromboembolism (VTE) in patients undergoing elective total hip and knee replacement surgery (2-5)
  • Acute treatment of deep vein thrombosis (DVT) or primary embolism (PE) (6,7)
  • Prevention of recurrent DVT or PE8

The company recently announced it had submitted applications to U.S. and EU regulatory authorities to review Pradaxa® for use in patients with DVT and PE.

Current Pradaxa® Research Underway
Currently, there are 12 Boehringer Ingelheim-sponsored trials of Pradaxa® in progress. These include studies which investigate Pradaxa® in patients with impaired renal function, as well as paediatric patients, and studies which explore management strategies for gastrointestinal symptoms. An investigational antidote is progressing through phase I clinical research for the reversal of Pradaxa®-induced anticoagulation.(13)

Additionally, the company is collecting important data on the use of Pradaxa® in clinical practice with ongoing long-term study programmes and registries. The GLORIATM-AF Registry Program is set to become one of the largest worldwide registries with the objective of understanding the long-term use of oral antithrombotic therapies in the prevention of non-valvular AF-related strokes in a real-world setting. Currently, the GLORIATM-AF Registry Program actively recruiting in 35 countries, with a planned enrolment of up to 56,000 patients worldwide. In addition, Boehringer Ingelheim is working in close collaboration with leading hospitals, insurance, healthcare research and governmental organisations in the USA to further assess the real-world clinical usage of Pradaxa®.

Current Experience with Pradaxa®
Globally, Pradaxa® is currently approved in over 100 countries for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and primary prevention of VTE following total hip replacement or total knee replacement surgery.(1,14) The extensive in-market experience of over 2 million patient-years puts Pradaxa® first among the novel oral anticoagulants. Since its approval in NVAF, Pradaxa® is estimated to have prevented up to 93,000 strokes in NVAF patients compared to no treatment.(1) Combined experience from the clinical trials programme and real-world clinical practice establish Pradaxa® as the longest and most extensively studied novel oral anticoagulant.(1)

About Pradaxa® (dabigatran etexilate)
Prescribing experience with Pradaxa® continues to grow with over two million patient-years of experience in all licensed indications globally.(1)

Pradaxa® is approved in over 100 countries worldwide.(1) It is licensed for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and for the primary prevention of venous thromboembolism in patients undergoing total hip replacement or total knee replacement surgery.(14)

Pradaxa®, a direct thrombin inhibitor (DTI),(15) was the first of a new generation of direct oral anticoagulants 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.

About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 140 affiliates and more than 46,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.

As a central element of its culture, Boehringer Ingelheim pledges to act socially responsible. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim's endeavors.

In 2012, Boehringer Ingelheim achieved net sales of about 14.7 billion euro. R&D expenditure in the business area Prescription Medicines corresponds to 22.5% of its net sales.

1. Boehringer Ingelheim data on file
2. Eriksson BI. et al. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet. 2007;370:949–56.
3. Eriksson BI. et al. Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II*). A randomised, doubleblind, non-inferiority trial. Thromb Haemost. 2011;105(4):721-9.
4. Eriksson BI. et al. Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J Thromb Haemost. 2007;5:2178–85.
5. Ginsberg JS. et al. Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. J Arthoplasty. 2009;24(1)1–9.
6. Schulman S. et al. Dabigatran versus warfarin in the Treatment of Acute Venous Thromboembolism. N Engl J Med. 2009;361:2342–52.
7. Schulman S. et al. A Randomized Trial of Dabigatran Versus Warfarin in the Treatment of Acute Venous Thromboembolism  (RE-COVER II). Oral presentation from Session 332: Antithrombotic Therapy 1. Presented on 12 December at the American Society of Hematology (ASH) Annual Meeting 2011.
8. Schulman S. et al. Extended Use of Dabigatran, Warfarin or Placebo in Venous Thromboembolism. N Engl J Med. 2013;368:709–18.
9. Connolly SJ. et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139-51.
10. Connolly SJ. et al. Newly identified events in the RE-LY® trial. N Engl J Med. 2010;363:1875-6.
11. Connolly S. J. et al. The Long Term Multi-Center Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) study. Circulation. 2013;128:237-243.
12. Oldgren J. et al. Dabigatran vs. placebo in patients with acute coronary syndromes on dual antiplatelet therapy: a randomized, double-blind, phase II trial. Eur Heart J. 2011;32:2781-9.
13. van Ryn J. et al. Reversal of dabigatran clotting activity in the rat ex vivo by a specific and selective antibody fragment antidote: are there non-specific effects on warfarin, rivaroxaban and apixaban? Poster P4848 to be presented on 3 September 2013 at ESC Congress 2013 (31 August – 4 September, Amsterdam, The Netherlands)
14. Pradaxa Summary of Product Characteristics, 2013
15. Di Nisio M, et al. Direct thrombin inhibitors. N Engl J Med. 2005; 353:1028-40.