Application submitted to the EMA for use of Pradaxa® in treatment of DVT and PE and prevention of recurrent DVT and PE

Boehringer Ingelheim today announced the submission of an application to the European Medicines Agency (EMA) for use of Pradaxa® (dabigatran etexilate) for the treatment of acute deep vein thrombosis (DVT) and pulmonary embolism (PE) and the prevention of recurrent DVT and PE.*

“Given the risk of potentially fatal consequences and recurrences of a deep vein thrombosis or pulmonary embolism, there is a need for safe and effective therapies to improve outcomes for patients,” said Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. “Our studies have demonstrated that Pradaxa® offers an effective treatment with significant safety benefits compared to warfarin both for acute treatment as well as in the long-term prevention of recurrent events. We are convinced that this treatment option can provide benefits to patients with acute DVT or PE, or those at risk of recurrent DVT and PE.”

The EMA submission is based on the results of four global Phase III studies investigating the efficacy and safety of Pradaxa® in the treatment of acute DVT and PE and in secondary prevention of recurrent DVT and PE.^1,2,3 In these studies, Pradaxa® was proven to be as effective as warfarin, with lower rates of clinically relevant bleeding (which includes major bleeding) and total bleeding for patients with DVT or PE.1,2,3 When compared to placebo, Pradaxa® prevented nine out of ten episodes of recurrent DVT and PE.¹ The results of the RE-COVER®, RE-MEDYTM and RE-SONATE® studies have been published in the New England Journal of Medicine.^1,2 All studies are part of the extensive RE-VOLUTION® clinical trial programme investigating Pradaxa® in multiple indications.

Pradaxa® is already widely approved for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and for the primary prevention of venous thromboembolic events in patients undergoing elective total hip replacement and total knee replacement surgery.4 In-market experience with Pradaxa® already spans over 1.6 million patient-years in all currently licensed indications in over 100 countries worldwide.⁵

Pradaxa® is currently not approved for the acute treatment or prevention of recurrent DVT and PE.

About DVT and PE

DVT, and its potentially fatal acute complication PE, are collectively termed venous thromboembolism (VTE), estimated to be the third most common cardiovascular disorder after coronary heart disease and stroke.⁶ A venous thrombosis is a blood clot (thrombus) that forms within a vein.^7,8 Most often, it develops in the deep veins of the leg or pelvis and is known as deep vein thrombosis. An embolism occurs if the clot, or a part of it, breaks off from the site of formation and travels through the circulatory system. If the clot lodges in the lung a potentially fatal condition, pulmonary embolism, occurs.⁸

Over 750,000 DVT or PE events are estimated to occur annually in six major EU countries (France, Germany, Italy, Spain, Sweden, UK), and over 900,000 events occur annually in the U.S.^9,10 Figures for the six European countries show that venous thrombotic events kill more people than AIDS, breast cancer, prostate cancer, and traffic accidents combined.⁹ The risk of experiencing a recurrent DVT or PE event increases cumulatively in patients who are not treated with standard therapy, up to 40% after 10 years.¹¹

In addition, up to 60% of people with DVT develop post thrombotic syndrome (PTS) with two years, and 4% of people with PE develop chronic thromboembolic pulmonary hypertension.^12,13

Given its prevalence, associated morbidity, mortality and chronic complications, DVT and PE are costly conditions, which put a significant burden on healthcare systems worldwide. Annual costs are estimated to be more than €3.07 billion in Europe for total direct costs associated with venous thrombotic events and up to $15.5 billion in the U.S. for diagnosis and treatment of DVT and PE.^7,14

About dabigatran etexilate (Pradaxa®)

Pradaxa® is already approved in over 100 countries worldwide.⁵ In Europe, Pradaxa® is licensed for the below indications: ⁴

• Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation
• Primary prevention of venous thromboembolic events in patients undergoing total hip replacement and
• Primary prevention of venous thromboembolic events in patients undergoing total knee replacement surgery

In addition, in 2013 Boehringer Ingelheim submitted a new application to the European Medicines Agency for Pradaxa® for the following indications:

• Treatment of acute deep vein thrombosis (DVT) and/or pulmonary embolism (PE) and prevention of related death
• Prevention of recurrent deep vein thrombosis (DVT) and/or pulmonary embolism (PE) and related death5

Important Notice: Pradaxa® (dabigatran etexilate) is currently not approved for the acute treatment or prevention of recurrent deep vein thrombosis or pulmonary embolism

Dabigatran etexilate, a direct thrombin inhibitor (DTIs)15, was the first of a new generation of 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 RE-VOLUTION®

The RE-VOLUTION® trial programme encompasses studies in primary DVT prevention, acute DVT and PE treatment, secondary DVT and PE prevention, stroke prevention in atrial fibrillation.

References

1. Schulman S, et al. Extended Use of Dabigatran, Warfarin or Placebo in Venous Thromboembolism. N Engl J Med. 2013;368:709-18.
2. Schulman S, et al. Dabigatran versus Warfarin in the Treatment of Acute Venous Thromboembolism. N Engl J Med. 2009;361:2342-52.
3. Schulman S, et al. A Randomized Trial of Dabigatran Versus Warfarin in the Treatment of Acute Venous Thromboembolism (RE-COVER II). 2011;118: Oral presentation from Session 332: Antithrombotic Therapy 1. Presented on 12 December at the American Society of Hematology (ASH) Annual Meeting 2011.
4. Pradaxa® European Summary of Product Characteristics 2013.
5. Boehringer Ingelheim. Data on file.
6. Goldhaber SZ. Pulmonary embolism thrombolysis: a clarion call for international collaboration. J Am Coll Cardiol. 1992;19:246-47.
7. Coalition to Prevent VTE. The Burden of VTE. Available at: http://www.coalitiontopreventvte.org/INDEX_CFM/T/THE_BURDEN_OF_VTE/OBJECTID/866876ED_1422_16B3_78D29387FBC3/VID/9E7D3566_C09F_296A_6111019937AE/CONTAINERID/666415AA_C09F_296A_61DB66942768/DISPLAYMETHOD/DISPLAY_ARTICLE.HTM Last accessed June 2013
8. Centers for Disease Control. Are You at Risk for Deep Vein Thrombosis? Available at: www.cdc.gov/Features/Thrombosis/index.html Last accessed May 2013
9. Cohen AT. et al. Venous thromboembolism (VTE) in Europe. Thromb Haemost. 2007;98:756-64.
10. Roger VL. et al. Heart disease and stroke statistics—2012 update: A report from the American Heart Association. Circulation. 2012;125(1):e2-e220.
11. Prandoni P. et al. The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients. Haematologica. 2007;92(2):199–205.
12. Ashrani AA. Incidence and cost burden of post-thrombotic syndrome. J Thromb Thrombolysis. 2009;28:465-76.
13. Pengo V. et al. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med. 2004;350:2257-64.
14. Medscape. Anticoagulation Therapy for Venous Thromboembolism. Medscape General Medicine. 2004;6(3):5
15. Di Nisio M, et al. Direct thrombin inhibitors. N Engl J Med 2005;353:1028-40.

*Important Notice: Pradaxa® (dabigatran etexilate) is currently not approved for the acute treatment or prevention of recurrent deep vein thrombosis and pulmonary embolism