FDA Advisory Committee Unanimously Recommends Approval of Dabigatran Etexilate for Stroke Prevention in Atrial Fibrillation

RIDGEFIELD, Conn., Sept. 20 /PRNewswire/ -- The U.S. Food and Drug Administration (FDA) Cardiovascular and Renal Drugs Advisory Committee today voted 9 to 0 in favor of approving dabigatran etexilate for stroke prevention in patients with atrial fibrillation (AFib).  An estimated 2.3 million Americans have AFib(1) and the prevalence is expected to increase 2.5 fold to 5.6 million by 2050,(1) reflecting the growing population of elderly individuals. (1)

For 50 years, warfarin has been the only oral anticoagulant available in the U.S. for stroke prevention in patients with AFib. Current guidelines for patients with non-valvular AFib treated with warfarin recommend maintaining an INR control range of 2.0-3.0 through regular blood monitoring and dose adjustments.(2) The RE-LY study established the safety and efficacy profile of dabigatran(3) without INR monitoring, dose adjustments or food restrictions.(3)

"We are pleased with the committee's unanimous recommendation, which marks an important step in advancing care for patients with atrial fibrillation," said Christopher Corsico, M.D., M.P.H., U.S. medical director, Boehringer Ingelheim Pharmaceuticals, Inc. "We believe dabigatran etexilate will offer patients and doctors the first new treatment option for stroke prevention in atrial fibrillation in more than 50 years. We look forward to working with the FDA as it finalizes its review of dabigatran."

About the RE-LY® Trial

RE-LY® was a global, Phase III, randomized trial of 18,113 patients enrolled in 951 centers in 44 countries,(3) investigating whether dabigatran etexilate (two blinded doses) was as effective as well-controlled warfarin – INR 2.0 - 3.0 – (open label) for stroke prevention.(3) Patients with non-valvular AFib and at least one other risk factor for stroke (i.e., previous ischemic stroke, transient ischemic attack, or systemic embolism, left ventricular dysfunction, age greater than or equal to 75 years, age greater than or equal to 65 years with either diabetes mellitus, history of coronary artery disease, or hypertension)(3) were enrolled in the study for two years with a minimum follow-up period of one year.(3)

The RE-LY® trial utilized the established PROBE (prospective, randomized, open-label, blinded endpoint evaluation) clinical trial protocol,(4) which has been used in the majority of previous trials of anticoagulation for stroke prevention in patients with AFib.(4) A PROBE design is more reflective of the differences in the management of warfarin and dabigatran in clinical practice.(4)  

In the RE-LY® trial, all clinical outcomes were adjudicated in a blinded manner to minimize bias in assessment of outcomes for each treatment.(4)

Bleeding and gastrointestinal events were the most commonly reported adverse events in this trial.(3)

About atrial fibrillation and stroke

Atrial fibrillation is the most common significant heart rhythm disorder(1) and is associated with up to 15 percent of all strokes in the U.S.(5) Atrial fibrillation is associated with nearly a five-fold increased risk of stroke,(5) and atrial fibrillation-related strokes can be about twice as likely to be fatal(6) or severely disabling as non-atrial fibrillation-related strokes.(7) The annual cost of stroke among Medicare atrial fibrillation patients is estimated to be $8 billion.(8)

About dabigatran etexilate

Dabigatran etexilate is not approved by the FDA. Dabigatran etexilate is an investigational oral direct thrombin inhibitor(9) being studied in the prevention and treatment of acute and chronic thromboembolic diseases.(3),(10),(11),(12),(13),(14),(15),(16)

About Boehringer Ingelheim Pharmaceuticals, Inc.

Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 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.

In 2009, Boehringer Ingelheim posted net sales of US $17.7 billion (12.7 billion euro) while spending 21% of net sales in its largest business segment, Prescription Medicines, on research and development.

For more information, please visit http://us.boehringer-ingelheim.com and follow us on Twitter at http://twitter.com/boehringerus.

(1) Go AS, et al. "Prevalence of Diagnosed Atrial Fibrillation in Adults: National Implications for Rhythm Management and Stroke Prevention: the AnTicoagulation and Risk Factors In Atrial Fibrillation (ATRIA) Study." Journal of the American Medical Association. 2001; 285(18):2370-2375.

(2) Fuster, V et al. "Atrial Fibrillation: Developed in Collaboration With the European Heart Committee to Revise the 2001 Guidelines for the Management of Patients With the European Society of Cardiology Committee for Practice Guidelines (Writing Cardiology/American Heart Association Task Force on Practice Guidelines and Fibrillation—Executive Summary: A Report of the American College of ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Rhythm Association and the Heart Rhythm Society." Circulation. 2006;114;700-752.

(3) Connolly SJ, et al. "Dabigatran versus Warfarin in Patients with Atrial Fibrillation." New England Journal of Medicine. 2009; 361.

(4) Ezekowitz MD, et al. "Rationale and Design of RE-LY: Randomized Evaluation of Long-Term Anticoagulation Therapy, Warfarin, Compared with Dabigatran." American Heart Journal.  2009; 157:805-810.

(5) Wolf PA et al. "Atrial Fibrillation as an Independent Risk Factor for Stroke: The Framingham Study." Stroke. 1991; 22:983-988.

(6) Lin HJ, et al. "Stroke Prevention in Atrial Fibrillation: The Framingham Study." Stroke. 1996; 27:1760-1764.

(7) Dulli D, et al. "Atrial Fibrillation is Associated with Severe Ischemic Stroke." Neuroepidemiology. 2003; 22:118-123.

(8) Caro, J. "An Economical Model of Stroke in Atrial Fibrillation: The Cost of Suboptimal Oral Anticoagulation." The American Journal of Managed Care. 2004; 10:S451-S461.

(9) Di Nisio, et al. "Direct Thrombin Inhibitors." New England Journal of Medicine. 2005; 353: 1028-40.

(10) Eriksson BI, et al. "Dabigatran Etexilate Versus Enoxaparin for Prevention of Venous Thromboembolism After Total Hip Replacement: a Randomized, Double-Blind, Non-Inferiority Trial." The Lancet. 2007; 370:949-956.

(11) The RE-MOBILIZE Writing Committee. "Oral Thrombin Inhibitor Dabigatran Etexilate vs North American Enoxaparin Regimen for Prevention of Venous Thromboembolism After Knee Arthroplasty Surgery." The Journal of Arthroplasty. 2009; 24:1-9.

(12) 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." Journal of Thrombosis and Haemostasis. 2007; 5: 2178-2185.

(13) ClinicalTrials.gov. "A Phase III Randomised, Parallel Group, Double-Blind, Active Controlled Study to Investigate the Efficacy and Safety of Orally Administered 220 mg Dabigatran Etexilate Capsules (110 mg Administered on the Day of Surgery Followed by 220 mg Once Daily) Compared to Subcutaneous 40 mg Enoxaparin Once Daily for 28-35 Days, in Prevention of Venous Thromboembolism in Patients With Primary Elective Total Hip Arthroplasty Surgery. (RE-NOVATE II)."  Available at: http://www.clinicaltrials.gov/ct2/show/NCT00657150?term=dabogatran&rank=7. Accessed on: January 28, 2009.

(14) ClinicalTrials.gov. "A Randomised, Multicenter, Double-Blind, Active Controlled Study to Investigate the Efficacy and Safety of Dabigatran Etexilate, 150 mg b.i.d Administered Orally (Capsules) for 18 Months, Compared to Warfarin Tablets p.r.n. (Target INR) for the Secondary Prevention of Venous Thromboembolism." Available at: http://www.clinicaltrials.gov/ct2/show/NCT00329238?term=dabigatran&rank=12. Accessed on: January 28, 2009.

(15) ClinicalTrials.gov. "A Phase III, Randomised, Double Blind, Parallel-Group Study of the Efficacy and Safety of Oral Dabigatran Etexilate (150 mg Bid) Compared to Warfarin (INR 2.0-3.0) for 6 Month Treatment of Acute Symptomatic Venous Thromboembolism, Following Initial Treatment (5-10 Days) With a Parenteral Anticoagulant Approved for This Indication." Available at: http://www.clinicaltrials.gov/ct2/show/NCT00680186?term=dabigatran&rank=5. Accessed on: January 28, 2009.

(16) ClinicalTrials.gov. "RELY-ABLE Long Term Multi-center Extension of Dabigatran Treatment in Patients with Atrial Fibrillation Who Completed RE-LY Trial to Assess the Effect of a Knowledge Translation Intervention on Patient Outcomes." Available at: http://www.clinicaltrials.gov/ct2/show/NCT00808067?term=dabigatran&rank=10. Accessed on: July 23, 2009.  

SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.