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Data From Largest Stroke Prevention Trial in Atrial Fibrillation To Premiere at European Society of Cardiology Congress

- RE-LY Findings to be Featured in “Hot-Line” Session with Simultaneous Publication in Leading Medical Journal -

Ridgefield, CT, August 25, 2009 - Results of the Phase III RE-LY® (Randomized Evaluation of Long-Term Anticoagulant Therapy, Warfarin, Compared to Dabigatran) study will be presented at the European Society of Cardiology (ESC) Congress in Barcelona on Sunday, Aug. 30.  The primary objective of RE-LY was to assess the safety and efficacy of the investigational oral direct thrombin inhibitor, dabigatran etexilate, against the current standard therapy, warfarin, for the prevention of stroke in patients with atrial fibrillation (AF).¹

Atrial fibrillation affects approximately 2.3 million Americans² and can increase the risk of stroke five-fold³ . Top-line findings from the 18,113 patient RE-LY study¹ will be featured in an ESC press briefing on Sunday, Aug. 30 at 8:00 a.m. CEST, with the full results presented in a “Hot-Line” session at 11:00 a.m. CEST.  The study will also be simultaneously published in a leading peer-reviewed medical journal.

Dabigatran etexilate is an investigational oral anticoagulant in Phase III development for stroke prevention in AF¹ and several other therapeutic areas, including prevention of atherothrombotic events in patients with acute coronary syndrome,⁴ as well as primary prevention,^5,6,7 secondary prevention⁸ and treatment of venous thromboembolism.⁹  Dabigatran etexilate is not yet approved by the U.S. Food and Drug Administration.

In addition to the primary findings, a RE-LY sub-analysis of treatment naïve patients will also be presented during a “Clinical Trial Update” session on Wednesday, Sept. 2 at 8:00 a.m. CEST.

About RE-LY: The largest AF outcomes trial to date
RE-LY was a global, Phase III, randomized trial of 18,113 patients¹ enrolled in more than 900 centers in 44 countries,¹ investigating whether dabigatran etexilate (two blinded doses) was as effective as well-controlled warfarin – INR 2.0-3.0 – (open label) for stroke prevention.¹ Patients with non-valvular AF and at least one other risk factor for stroke (i.e., previous ischemic stroke, transient ischemic attack, or systemic embolism, left ventricular dysfunction, age > 75 years, age > 65 years with either diabetes mellitus, history of coronary artery disease, or hypertension)¹ were enrolled in the study for two years with a minimum follow-up period of one year.¹

The primary endpoint of the trial was incidence of stroke (including hemorrhagic) and systemic embolism.¹⁰ Secondary outcome measures included a composite of incidence of stroke (including hemorrhagic), systemic embolism and all death, as well as a composite of incidence of stroke (including hemorrhagic), systemic embolism, pulmonary embolism, acute myocardial infarction, and vascular death (including death from bleeding).¹⁰ Additional safety endpoints included bleeding events (major and minor), intracerebral hemorrhage, other intracranial hemorrhage, elevations in liver transaminases, bilirubin and hepatic dysfunction, and other adverse events.¹

About AF and stroke
Atrial fibrillation is the most common heart rhythm abnormality in the U.S.,¹¹ accounting for one out of every three hospitalizations for irregular heart beat.¹¹ The prevalence of atrial fibrillation in the U.S. is expected to increase 2.5 fold to 5.6 million by 2050, reflecting the growing population of elderly individuals.² Atrial fibrillation is the cause of up to one out of every six strokes in the U.S.¹¹  Strokes related to AF are twice as likely to be fatal¹² and twice as likely to be debilitating as non-AF related strokes.¹³   Total annual costs for the treatment of AF are estimated to be more than U.S. $6.65 billion.¹⁴

About dabigatran etexilate
Dabigatran etexilate is a direct thrombin inhibitor (DTI),¹⁵ in a class of oral anticoagulants being studied in the prevention and treatment of acute and chronic thromboembolic diseases.^{1,4,5,6,7,8,9} Direct thrombin inhibitors provide an anticoagulant effect by specifically and selectively blocking the activity of thrombin (both free and clot-bound), the central enzyme in the process responsible for clot (thrombus) formation – conversion of fibrinogen to fibrin.¹⁵

Dabigatran etexilate is not approved by the FDA.  Dabigatran etexilate is approved and marketed as Pradaxa® in 40 countries for the primary prevention of venous thromboembolic events (blood clots) in patients who have undergone elective total hip or elective total knee replacement surgery.

About REVOLUTION®
RE-LY® is part of Boehringer Ingelheim’s extensive RE-VOLUTION clinical trial program – evaluating the efficacy and safety of dabigatran etexilate against current standard therapy in more than 38,000 patients.^{1,4,5,6,7,8,9,16,17} In addition to RE-LY, the development program encompasses studies in:

• Primary prevention of venous thromboembolism (VTE) in patients undergoing elective total hip and knee replacement surgeries ^5,6,7
• Treatment of acute VTE⁹
• Secondary prevention of VTE⁸
• Prevention of atherothrombotic events in patients with acute coronary syndrome⁴

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 138 affiliates in 47 countries and approximately 41,300 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 2008, Boehringer Ingelheim posted net sales of U.S. $17 billion (11.6 billion euro) while spending approximately one-fifth of net sales in its largest business segment, Prescription Medicines, on research and development.

For more information, please visit http://us.boehringer-ingelheim.com.

 

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References

1. 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.
2. 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.
3. Kannel WB, et al. "Final Draft Status of the Epidemiology of Atrial Fibrillation."  Medical Clinics of North America. 2008; 92(1):17-ix.
4. ClinicalTrials.gov.  “RandomizEd Dabigatran Etexilate Dose Finding Study in Patients With Acute Coronary Syndromes Post Index Event With Additional Risk Factors for Cardiovascular Complications Also Receiving Aspirin and Clopidogrel: Multi-Centre, Prospective, Placebo Controlled, Cohort Dose Escalation Study (RE-DEEM).”  Available at: http://www.clinicaltrials.gov/ct2/show/NCT00621855?term=dabigatran&rank=11.  Accessed on: January 28, 2009.
5. 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.
6. The RE-MOBILIZE Writing Committee. “Oral Thrombin Inhibitor Dabigatran Etexilate vs North American Enoxaprin Regiment for Prevention of Venous Thromboembolism After Knee Arthroplasty Surgery.” The Journal of Arthroplasty. 2009; 24:1-9.
7. 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
8. 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.
9. 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.
10. ClinicalTrials.gov. “Randomized Evaluation of Long Term Anticoagulant Therapy (RE-LY) With Dabigatran Etexilate.” Available at: http://clinicaltrials.gov/ct2/show/NCT00262600?term=dabigatran&rank=11. Accessed: March 11, 2009.
11. Fuster V, et al. “ACC/AHA/ESC Guidelines for the Management of Patients with Atrial Fibrillation.” Circulation. 2001; 104:2118-2150. 
12. Lin HJ, et al. “Stroke Prevention in Atrial Fibrillation: The Framingham Study.” Stroke. 1996; 27:1760-1764.
13. Dulli D, et al. “Atrial Fibrillation is Associated with Severe Ischemic Stroke.” Neuroepidemiology. 2003; 22:118-123.
14. Coyne KS, et al. “Assessing the Direct Costs of Treating Nonvalvular Atrial Fibrillation in the United States.” Value Health. 2006; 9:348–56.
15. Di Nisio M, et al. “Direct Thrombin Inhibitors.” New England Journal of Medicine. 2005; 353:1028-40.
16. ClinicalTrials.gov. “Twice-Daily Oral Direct Thrombin Inhibitor Dabigatran Etexilate in the Long-Term Prevention of Recurrent Symptomatic Proximal Venous Thromboembolism in Patients With Symptomatic Deep-Vein Thrombosis or Pulmonary Embolism.” Available at: http://www.clinicaltrials.gov/ct2/show/NCT00558259?term=dabigatran&rank=1. Accessed on: April 15, 2009.
17. 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.

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