• Recommendation for approval brings DVT and PE patients a step closer to a simple treatment option that is as effective as warfarin with significantly lower rates of bleeding1,2,3 • CHMP positive opinion follows recent U.S. FDA approval of Pradaxa® for treatment of and reduction in the risk of recurrent DVT and PE • Pradaxa® is already approved for stroke prevention in patients with atrial fibrillation and prevention of venous thromboembolism in patients undergoing total hip or knee replacement surgery4
For media outside of the U.S., the UK & Canada only
Ingelheim, Germany, 25 April, 2014 – Boehringer Ingelheim today announces that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending approval of Pradaxa® (dabigatran etexilate) in the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) and the prevention of recurrent DVT and PE in adults. The U.S. Food and Drug Administration (FDA) approved Pradaxa® for DVT and PE patients earlier this month.
DVT and PE are critical medical conditions: almost one in three PE patients die within three months and four out of 10 patients suffer a repeat blood clot within 10 years of the first. Furthermore, PE as a consequence of a DVT is the leading cause of preventable death in hospital.5,6 To avoid this, and to minimise a patient’s risk of experiencing another blood clot, effective and safe treatment is imperative.
Professor Klaus Dugi, Chief Medical Officer, Boehringer Ingelheim
"We are very pleased with this recommendation for European approval, which is an important step towards broadening the indications for which Pradaxa® can be used and extending its proven benefits to more patients," commented Professor Klaus Dugi, Chief Medical Officer, Boehringer Ingelheim. "With Pradaxa® we aim to offer physicians and patients a new, simple treatment option that is as effective as warfarin, the current standard of care, while providing a favourable overall safety profile."
The CHMP positive opinion is based on results from four robust phase III clinical trials involving almost 10,000 patients that demonstrated the efficacy of Pradaxa® in the treatment and prevention of repeat DVT and PE compared to warfarin. Data also show a 92% reduction in the risk of recurrent blood clots versus placebo.2 Results showed that DVT or PE patients taking Pradaxa® experienced significantly lower rates of bleeding than those taking warfarin, resulting in a favourable overall safety profile.3
Pradaxa® has the longest clinical trial experience in DVT and PE patients of any novel oral anticoagulant (NOAC).2,7,8 Pradaxa® will offer DVT and PE patients, and their physicians, a treatment option that is more convenient than both warfarin and other NOACs investigated in this indication, as it does not require routine dose monitoring, nor a mandatory dose change during the course of treatment. DVT and PE patients can start taking Pradaxa® in a simple fixed dose regimen after initial treatment with an injectable anticoagulant such as low-molecular-weight heparin (LMWH).
Clinical experience of Pradaxa® equates to over 2.9 million patient-years in all licensed indications worldwide. It has already been available for more than six years and is approved in over 100 countries to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF).9 Pradaxa® 150mg is the only NOAC which in its clinical trial vs. warfarin (RE-LY®)* has shown a significant reduction in the incidence of both ischaemic and haemorrhagic strokes in patients with NVAF.10,11 Ischaemic strokes, which account for nine out of 10 strokes experienced by patients with AF, can have devastating consequences and are often fatal or severely disabling.12,13
In the EU, Pradaxa® is also approved for primary prevention of VTE (venous thromboembolism, the collective term for DVT and PE) in patients who have undergone elective total hip or total knee replacement surgery.4
NOTES TO THE EDITORS
About Pradaxa® (dabigatran etexilate) Clinical experience of Pradaxa® (dabigatran etexilate) exceeds that of all other novel oral anticoagulants, equating to over 2.9 million patient-years in all licensed indications worldwide. Pradaxa® has been in the market for more than 6 years and is approved in over 100 countries.9
Currently approved indications for Pradaxa® are:
Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and a risk factor for stroke
Primary prevention of venous thromboembolic events in patients undergoing elective total hip replacement surgery
Primary prevention of venous thromboembolic events in patients undergoing elective total knee replacement surgery4
In the U.S. Pradaxa® is approved:
To reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation
For the treatment of deep vein thrombosis and pulmonary embolism in patients who have been treated with a parenteral anticoagulant for five to 10 days
To reduce the risk of recurrence of deep vein thrombosis and pulmonary embolism in patients who have been previously treated14
Additional registration processes for Pradaxa® in the treatment of DVT and PE, and prevention of recurrent DVT and PE continue in individual countries world-wide.
Pradaxa®, a direct thrombin inhibitor (DTI), was the first widely approved drug in a new generation of direct oral anticoagulants, available to target a high unmet medical need in the prevention and treatment of acute and chronic thromboembolic diseases.15,16 Potent antithrombotic effects are achieved with direct thrombin inhibitors by specifically blocking the activity of thrombin, the central enzyme in the process responsible for clot (thrombus) formation.17 In contrast to vitamin-K antagonists, which variably act via different coagulation factors, Pradaxa® provides effective, predictable and reproducible anticoagulation with a low potential for drug-drug interactions and no drug-food interactions, without the need for routine coagulation monitoring or mandatory dose adjustment.15,17
Boehringer Ingelheim The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, Boehringer Ingelheim operates globally with 142 affiliates and a total of more than 47,400 employees. The focus of the family-owned company, founded in 1885, is researching, developing, manufacturing and marketing new medications of high therapeutic value for human and veterinary medicine.
Taking social responsibility is an important element of the corporate culture at Boehringer Ingelheim. This includes worldwide involvement in social projects, such as the initiative "Making more Health" and caring for the employees. Respect, equal opportunities and reconciling career and family form the foundation of the mutual cooperation. In everything it does, the company focuses on environmental protection and sustainability.
In 2013, Boehringer Ingelheim achieved net sales of about 14.1 billion euros. R&D expenditure corresponds to 19.5% of its net sales.
* RE-LY® was a global, phase III, PROBE (prospective, randomized, open-label with blinded endpoint evaluation) design trial comparing two fixed doses of the oral direct thrombin inhibitor Pradaxa® (110mg and 150mg bid) each administered in a blinded manner, with open label warfarin.
References 1. Schulman S, et al. Dabigatran versus Warfarin in the Treatment of Acute Venous Thromboembolism. N Engl J Med. 2009;361:2342–52. 2. Schulman S, et al. Extended Use of Dabigatran, Warfarin or Placebo in Venous Thromboembolism. N Engl J Med. 2013;368:709–18. 3. Schulman S, Kakkar AK, Goldhaber SZ, et al. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation 2014;129:764-772. 4. Pradaxa® European Summary of Product Characteristics, 2014. 5. Heit JA, et al. Predictors of survival after deep vein thrombosis and pulmonary embolism. Arch Intern Med 1999;159:445–453. 6. BMJ Best Practice. VTE Prophylaxis. Available at: http://bestpractice.bmj.com/best-practice/monograph/1087.html. Last accessed: April 2014. 7. The EINSTEIN Investigators. Oral Rivaroxaban for Symptomatic Venous Thromboembolism. N Engl J Med 2010;363:2499–2510. 8. Agnelli G, et al. Apixaban for Extended Treatment of Venous Thromboembolism. N Engl J Med 2013;368:699–708. 9. Boehringer Ingelheim. Data on file. 10. Connolly SJ, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51. 11. Connolly SJ, et al. Newly identified events in the RE-LY trial. N Engl J Med. 2010;363:1875–6. 12. Gladstone DJ, et al. Potentially Preventable Strokes in High-Risk Patients With Atrial Fibrillation Who Are Not Adequately Anticoagulated. Stroke. 2009;40(1):235–40. 13. Andersen KK, et al. Hemorrhagic and ischemic strokes compared: stroke severity, mortality, and risk factors. Stroke. 2009;40(6):2068-72. 14. PRADAXA® Prescribing Information, 2014. Available at: http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing%20Information/PIs/Pradaxa/Pradaxa.pdf. Last accessed: April 2014. 15. Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47(5):285–95. 16. Di Nisio M, et al. Direct thrombin inhibitors. N Engl J Med. 2005;353:1028–40. 17. Stangier J, et al. Pharmacokinetic Profile of the Oral Direct Thrombin Inhibitor Dabigatran Etexilate in Healthy Volunteers and Patients Undergoing Total Hip Replacement. J Clin Pharmacol. 2005;45:555–63.