INGELHEIM, Germany--(BUSINESS WIRE)-- 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. 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*.
Dabigatran etexilate 150mg bid is the only novel oral anticoagulant proven superior to well-controlled warfarin treatment (Median TTR 67%)2 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.2-4 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.2-4 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,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
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.2-4
* 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.
1. Di Nisio M, et al. Direct Thrombin Inhibitors. N Engl J Med 2005; 353:1028-40.
2. FDA Advisory Committee Briefing Document, September 2010, http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisory Committee/UCM226009.pdf.
3. Connolly SJ, et al. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2009; 361:1139-51.
4. 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).
5. 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.
6. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991: 22(8);983-8.
7. 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.
8. Lin HJ, Wolf PA, Kelly-Hayes M, et al. Stroke severity in atrial fibrillation: the Framingham study. Stroke 1996; 27:1760-4.
9. 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.
10. Lloyd-Jones DM, Wang TJ, Leip EP, et al. Lifetime risk for development of atrial fibrillation. Circulation 2004;110:1042-6.
11. 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.
12. Kannel WB, et al. Final Draft Status of the Epidemiology of Atrial Fibrillation. Med Clin North Am. 2008; 92(1): 17–ix.
13. 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.
Boehringer Ingelheim GmbH
Dr. Reinhard Malin
Media + PR
Phone: + 49 - 6132 – 77 90815
Fax: + 49 - 6132 – 72 6601