Value through Innovation23 April 2014
15 April 2011

Dabigatran etexilate recommended for approval in atrial fibrillation for stroke prevention in Europe

The first novel breakthrough agent for stroke prevention in patients with AF in more than 50 years receives positive opinion in Europe

Ingelheim, Germany, 15. April 2011 – Boehringer Ingelheim's novel oral anticoagulant dabigatran etexilate (to be marketed under the trademark Pradaxa®), 1 received a positive opinion from the European Medicines Agency's (EMA) medicinal committee today.2 This positive opinion is a decisive step in making the breakthrough therapy available to millions of patients with atrial fibrillation (AF) at risk of stroke in the European Union.

The Committee for Medicinal Products for Human Use (CHMP) has recommended approval of dabigatran etexilate in the member states of the EU for the prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation with one or more risk factors *.2

Dabigatran etexilate 150mg bid is the only novel oral anticoagulant proven superior to well-controlled warfarin treatment (Median TTR 67%)3 in reducing stroke and systemic embolism in an intention-to-treat (ITT) analysis. The ITT analysis represents the highest standard for analysing superiority in non-inferiority trials. These groundbreaking results were shown in RE-LY®, a PROBE (prospective, randomized, open-label with blinded endpoint evaluation) trial designed to compare two fixed doses of the oral direct thrombin inhibitor dabigatran etexilate (110mg and 150mg bid) each administered in a blinded manner, with open label warfarin.3-5 Dabigatran etexilate 110 mg bid was shown to be as effective as warfarin. Both doses of dabigatran etexilate showed significantly lower intracranial bleeding compared to well-controlled warfarin.3-5 Dabigatran etexilate does not require routine coagulation monitoring or dose adjustments, is not affected by food and has a low potential for drug-drug interactions.

Up to three million people worldwide suffer strokes related to AF each year,6-8; which are typically severe and disabling, with one half of this population dying within one year.9 Strokes due to AF tend to be severe, with an increased likelihood of death (20%), and disability (60%).9

Professor Klaus Dugi Boehringer Ingelheim GmbH

Professor Klaus Dugi Boehringer Ingelheim GmbH

Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim, commented, "After 50 years, a more effective alternative to warfarin is finally being made available to patients. The positive opinion from the CHMP for dabigatran etexilate represents another significant milestone in the history of stroke prevention in AF. When approved in the EU, dabigatran etexilate (150mg bid) will improve the lives of many patients by significantly reducing the risk of strokes compared to warfarin and avoid immense suffering for a vast proportion of them."

Outside the EU dabigatran etexilate has been approved for stroke risk reduction in patients with AF in the USA, Canada, Japan, South Korea, New Zealand, Israel, Malaysia, Philippines, Singapore, Namibia, Colombia, Netherlands Antilles, Suriname and Indonesia; details of these approvals may however differ from the label recommended by CHMP.

The CHMP positive opinion is based on the results from the RE-LY® trial, the largest AF trial completed to date. The data showed that dabigatran etexilate 150mg bid significantly reduced the risk of stroke and systemic embolism by 35 percent in addition to significantly lowering the risk of life-threatening and intracranial bleeding compared to well controlled warfarin.3-5

NOTES TO EDITORS

About AF and stroke
AF is the most common heart rhythm condition,10 affecting nearly one in four people over the age of 4011 and 1% of the total population, rising to 10% in people over the age of 80.10 People with AF are more likely to experience blood clots, which increases the risk of stroke by five-fold.12,13 Up to three million people worldwide suffer strokes related to AF each year,5-7 which are typically severe and disabling, with one half of this population dying within one year.8 Strokes due to AF tend to be severe, with an increased likelihood of death (20%), and disability (60%).8 Many AF-related strokes can be prevented with appropriate antithrombotic therapy.14

About RE-LY®
RE-LY® (Randomized Evaluation of Long term anticoagulant therapY) was a global, phase III, PROBE (prospective, randomized, open-label with blinded endpoint evaluation) trial of 18,113 patients enrolled in over 900 centres in 44 countries designed to  compare two fixed doses of the oral direct thrombin inhibitor dabigatran (110mg and 150mg bid) each administered in a blinded manner, with well controlled (INR 2.0-3.0, median TTR 67%) open label warfarin.3-5 Patients were followed-up in the study for a median of 2 years with a minimum of 1 year follow-up.3,4

The primary endpoint of the trial was incidence of stroke (including haemorrhagic) or systemic embolism. Secondary outcome measures included all-cause death, incidence of stroke (including haemorrhagic), systemic embolism, pulmonary embolism, acute myocardial infarction, and vascular death (including death from bleeding).

Compared to well controlled warfarin, dabigatran etexilate showed in the trial: 3,4

  • Significant reduction in the risk of stroke and systemic embolism – including haemorrhagic strokes with dabigatran etexilate 150mg bid
  • Similar rates of stroke/systemic embolism with dabigatran etexilate 110mg bid
  • Significantly lower major bleeding events with dabigatran etexilate 110mg bid
  • Significantly lower life threatening and intracranial bleeding with both doses
  • Significant reduction in vascular mortality with dabigatran etexilate 150mg bid.

 

About dabigatran etexilate
Dabigatran etexilate is at the forefront of a new generation of oral anticoagulants/direct thrombin inhibitors (DTIs)1 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.

Dabigatran etexilate has already been approved for stroke risk reduction in patients with AF in 14 countries under the trademark Pradaxa® (In Canada: Pradax® and in Japan: Prazaxa®). Details of these approvals may however differ from the label recommended by CHMP.
It has also been approved for the primary prevention of venous thromboembolic events (blood clots) in adults who have undergone elective total hip or elective total knee replacement surgery in 83 countries under the trademark Pradaxa® (in Canada: Pradax®).

About the dabigatran etexilate clinical trial programme
Boehringer Ingelheim’s clinical trial programme to evaluate the efficacy and safety of dabigatran etexilate encompasses studies in:

  • Primary prevention of venous thromboembolism (VTE) in patients undergoing elective total hip and knee replacement surgeries
  • Treatment of acute VTE
  • Secondary prevention of VTE
  • Stroke prevention in AF.

Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 145 affiliates and more than 42,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

For Boehringer Ingelheim - and its employees - carrying a good share of social responsibility is an important component in its business culture. Both global commitments in social projects and properly caring for all its employees are included. Respect, equal opportunity, and the balance of career and family life form the basis for mutual cooperation. And, environmental protection and sustainability are always the main focus during any of Boehringer Ingelheim’s undertakings.

In 2010, Boehringer Ingelheim posted net sales of about 12.6 billion euro while spending almost 24% of net sales in its largest business segment Prescription Medicines on research and development.

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

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 USA or Canada.

*Previous stroke, transient ischemic attack, or systemic embolism (SEE); Left ventricular ejection fraction < 40 %; Symptomatic heart failure, ≥New York Heart Association (NYHA) Class 2; Age ≥75 years; Age ≥65 years associated with one of the following: diabetes mellitus, coronary artery disease, or hypertension.

References:

1. Di Nisio M, et al. Direct Thrombin Inhibitors. N Engl J Med 2005; 353:1028-40.
2. CHMP post-authorisation summary of positive opinion for Pradaxa, April 2011. http://www.ema.europa.eu/docs/en_GB/document_library/summary_of_opinion
/human/000829/WC500105283.pdf
3. FDA Advisory Committee Briefing Document, September 2010,http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeeting
Materials/Drugs/CardiovascularandRenalDrugsAdvisory Committee/UCM226009.pdf .
4. Connolly SJ, et al. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2009; 361:1139-51.
5. Connolly SJ, Ezekowitz MD, Yusuf S, Reilly PA, Wallentin L: Newly identified events in the RE-LY® trial. N Engl J Med 2010; 363(19): 1875-1876 (November 4th, 2010).
6. Atlas of Heart Disease and Stroke, World Health Organization, September 2004. Viewed July 2009 at http://www.who.int/cardiovascular_diseases/en/cvd_atlas_15_burden_stroke.pdf.
7. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991: 22(8);983-8.
8. Marini C, De Santis F, Sacco S, et al. Contribution of atrial fibrillation to incidence and outcome of ischaemic stroke: results from a population-based study. Stroke 2005; 36:1115-9.
9. Lin HJ, Wolf PA, Kelly-Hayes M, et al. Stroke severity in atrial fibrillation: the Framingham study. Stroke 1996; 27:1760-4.
10. Stewart S, Murphy N, Walker A, et al. Cost of an Emerging Epidemic: an Economic Analysis of Atrial Fibrillation in the UK. Heart 2004; 90:286-92.
11. Lloyd-Jones DM, Wang TJ, Leip EP, et al. Lifetime risk for development of atrial fibrillation. Circulation 2004;110:1042-6.
12. Fuster V, Rydn LE, Cannom DS, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation – executive summary. Circulation 2006; 114:700-52.
13. Kannel WB, et al. Final Draft Status of the Epidemiology of Atrial Fibrillation. Med Clin North Am. 2008; 92(1): 17–ix.
14. Hart RG, Benavente O, McBride R, Pearce LA. Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis. Ann Intern Med 1999; 131:492-501.

Media Contact - Science, Research & Development, CNS, Oncology, Hepatitis

Media Contact - Science, Research & Development, CNS, Oncology, Hepatitis

Follow Boehringer Ingelheim 

Follow us on Twitter