New data on safety and efficacy of Pradaxa® in treatment of acute deep vein thrombosis and pulmonary embolism

• New safety data consistently favour Pradaxa® (dabigatran etexilate) over warfarin for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE)1
• Pooled analysis of two phase III trial data shows significantly lower clinically relevant bleeding rates for Pradaxa® vs. warfarin1
• Findings support previous data, confirming efficacy of Pradaxa® in the treatment of DVT and PE2,3

For media outside of the US, the UK & Canada only

Ingelheim, Germany, 17 December, 2013 – New pooled safety data from the RE-COVERTM and RE-COVERTM II phase III trials in acute deep vein thrombosis (DVT) and pulmonary embolism (PE) consistently favour treatment with Pradaxa® 150mg bid over treatment with warfarin. The data are published online today in Circulation.1

Vitamin K antagonists (VKAs), the current standard of care in DVT and PE patients after an initial course of parenteral anticoagulation, are associated with multiple limitations and treatment challenges including inconvenience to both patients and physicians.4,5 Currently, warfarin is implicated in one third of all emergency hospitalisations for adverse drug events and there is a need for alternative, safer and simpler treatment options.6

RE-COVERTM and RE-COVERTM II, both global phase III randomised double-blind parallel-group studies, investigated the efficacy and safety of Pradaxa® versus warfarin for the treatment of acute DVT or PE.1,2 Primary efficacy outcomes were recurrent symptomatic venous thromboembolism (VTE) and related deaths with a safety endpoint of major bleeding measured during six months of therapy.1,2 The combined studies enrolled 5,107 patients who were all initially treated with parenteral heparin therapy and then randomised to receive warfarin or Pradaxa®.1

When looking at the total treatment period including initial heparin treatment, the pooled data show a statistically significantly lower incidence of clinically relevant bleeding events (Pradaxa® 150mg vs. warfarin, HR 0.62) and total bleeding (Pradaxa® 150mg vs. warfarin, HR 0.70) for patients treated with heparin followed by Pradaxa® compared to patients receiving heparin followed by warfarin.1 These data also show a trend towards reduction of major bleeding for Pradaxa® (Pradaxa® 150mg 1.4% vs. warfarin 2.0%).1 The primary efficacy endpoint of VTE or related death was comparable between the two treatments (Pradaxa® 150mg 2.4% vs. warfarin 2.2%).1​

Importantly, pooled data for the treatment period after the end of the heparin treatment when patients were receiving only the oral study drugs (Pradaxa® or warfarin) show that versus warfarin, patients treated with Pradaxa® have statistically significantly lower rates of: 1

  • Major bleeding events (Pradaxa® 150mg vs. warfarin, HR 0.60, CI 0.36-0.99)
  • Major or clinically relevant bleeding (Pradaxa® 150mg vs. warfarin, HR 0.56, CI 0.45-0.71)
  • Total bleeding events (Pradaxa® 150mg vs. warfarin, HR 0.67, CI 0.59-0.77)

Sam Schulman, Professor of Hematology and Thromboembolism, Department of Medicine, McMaster University, Hamilton, Canada
Sam Schulman,
Professor of
Hematology and
Thromboembolism,
Department of
Medicine, McMaster
University, Hamilton,
Canada

"These latest results from the pooled analysis of the phase III trials RE-COVERTM and RE-COVERTM II reinforce that dabigatran etexilate is an effective treatment with a favourable safety profile in DVT and PE. The pooled data favour dabigatran treatment over warfarin and provide further reassurance to both physicians and patients especially regarding the safety of the treatment", commented Sam Schulman, Professor of Hematology and Thromboembolism, Department of Medicine, McMaster University, Hamilton, Canada.

Existing data show that in the acute treatment and prevention of recurrent DVT and PE, Pradaxa® 150mg bid offers an effective and well-tolerated treatment.2,3 Pradaxa®'s fast onset of action, providing maximal effectiveness in less than two hours, allows for an easy transition from initial heparin treatment with no overlap in treatment required.7 Due to one fixed-dose treatment with Pradaxa® from the beginning, patient management is simplified, as there is no need to titrate or adjust once prescribed.7

Pradaxa® is already widely approved for stroke prevention in atrial fibrillation and for primary prevention of VTE following total hip replacement or total knee replacement surgery.7 Collective clinical experience exceeds six years, with two million patient-years in all licensed indications placing Pradaxa® first among the novel oral anticoagulants.8,9

Important note: Pradaxa® (dabigatran etexilate) is currently not approved for the acute treatment of DVT or PE.

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 million patient-years in all licensed indications worldwide.8 Pradaxa® has already been in the market for more than 5 years and is approved in over 100 countries
Currently approved indications for Pradaxa® are:7​

  • Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF) 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 surgery

In June 2013 Boehringer Ingelheim started submitting new applications to regulatory authorities for Pradaxa® for the following indications:8

  • 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 death

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

Pradaxa®, a direct reversible 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.7,10 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.11 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 dose adjustment.10,12

About Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE)​
A venous thrombosis is a blood clot (thrombus) that forms within a vein. Most often, it develops in the deep veins of the leg or pelvis and is known as a deep vein thrombosis (DVT). 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 then a potentially fatal pulmonary embolism (PE) may occur.13 Venous thromboembolism (VTE) is estimated to be the third most common cardiovascular disorder after coronary heart disease and stroke.14 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.15​

Anticoagulant treatment is the standard therapy against venous blood clots.16​

For more information on the prevalence, medical background and societal burden of DVT or PE please visit: http://www.newshome.com/dvt-pe.aspx​

About the Pradaxa® (dabigatran etexilate) clinical trial programme
Since its discovery, 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, encompassing studies in:1-3, 9,17-23

  • Stroke prevention in AF
  • Primary prevention of VTE in patients undergoing elective total hip replacement surgery
  • Primary prevention of VTE in patients undergoing elective total knee replacement surgery
  • Treatment of acute DVT or PE
  • Prevention of recurrent DVT or PE

In line with Boehringer Ingelheim’s commitment to research and scientific development the clinical trial programme for Pradaxa® is ongoing.

About Pradaxa® (dabigatran etexilate) DVT and PE clinical trials
The Boehringer Ingelheim clinical trials investigating Pradaxa® in the prevention and treatment of DVT and PE (collectively venous thromboembolism or VTE) are part of the extensive RE-VOLUTION® trial programme. Results from phase III trials demonstrate Pradaxa® has a good efficacy and safety profile across primary prevention and treatment of acute as well as prevention of recurrent DVT and PE events: 1-3, 17-20

  • In preventing VTE after total knee or hip replacement surgery, Pradaxa® has been studied in four trials (RE-NOVATE®, RE-NOVATE II®, RE-MODELTM and RE-MOBILIZE®) including more than 10,000 patients. The trials have shown that Pradaxa® is as effective as once daily enoxaparin with a similar safety profile.17-20
  • For the treatment of acute DVT or PE, Pradaxa® has been studied in two trials (RE-COVER™ and RE-COVER™ II) including over 5,000 patients. The trials have shown that Pradaxa® is comparable to standard of care, and has a favourable safety profile.1,2​
  • For the prevention of recurrent DVT or PE, which was investigated in two trials (RE-MEDY™ and RE-SONATE™) including over 4,000 patients, Pradaxa® is comparable to warfarin and showed a significant reduction in the incidence of recurrent DVT or PE compared to placebo. Major bleeding rates observed were low and confirmed again the favourable safety profile.3

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.

Social responsibility is a central element of Boehringer Ingelheim's culture. 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 endeavours.

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.

Please be advised
This release is from Boehringer Ingelheim Corporate Headquarters in Germany. Please be aware that there may be national differences between countries regarding specific medical information, including licensed uses. Please take account of this when referring to the information provided in this document. This press release is not intended for distribution within the U.S., the UK or Canada.

Referências

  1. Schulman S, et al. Treatment of Acute Venous Thromboembolism with Dabigatran or Warfarin and Pooled Analysis. Circulation published online before print December 16, 2013, doi:10.1161
  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. Extended Use of Dabigatran, Warfarin or Placebo in Venous Thromboembolism. N Engl J Med. 2013;368:709–18.
  4. Haas S. New oral Xa and IIa inhibitors: updates on clinical trial results. J Thromb Thrombolysis .2008;25(1):52-60.
  5. Schulman S, et al. Hemorrhagic complications of anticoagulant and thrombolytic treatment: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133:257S-98S.
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  7. Pradaxa® European Summary of Product Characteristics, 2013
  8. Boehringer Ingelheim data on file.
  9. Ezekowitz M, et al. RE-LY and RELY-ABLE: Long-term Follow-up of Patients With Nonvalvular. Atrial Fibrillation Receiving Dabigatran Etexilate for Up to 6.7 Years. Oral presentation #10684 on Monday 18 November 2013 at the American Heart Association’s Scientific Sessions, Dallas, Texas, USA.
  10. Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47(5):285–95.
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  17. 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.
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  19. 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.
  20. 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.
  21. Connolly SJ, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139-51.
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