ADDING and REPLACING Milestone Results in RE-COVER™ Study – Novel Oral Direct Thrombin Inhibitor Dabigatran Etexilate – as Effective as Well Controlled Warfarin with Less Bleeding in Treatment of Acute Venous Thromboembolism

NEW ORLEANS--(BUSINESS WIRE)--Add after tenth graph of release: For further information, including editors notes and references, please visit http://www.boehringer-ingelheim.com/news/news_releases/press_releases/2009/06_december_2009.html

“Following the outstanding results from the RE-LY® trial, these impressive new data mean dabigatran etexilate has the potential to benefit even more patients and overtake warfarin as the treatment of choice”

The corrected release reads:

Milestone Results in RE-COVER™ Study – Novel Oral Direct Thrombin Inhibitor Dabigatran Etexilate – as Effective as Well Controlled Warfarin with Less Bleeding in Treatment of Acute Venous Thromboembolism

Compared to well controlled warfarin, dabigatran etexilate showed:¹

Equal efficacy in the reduction of recurrent venous thromboembolism (VTE) and deaths related to VTE
Significantly less bleeding events
Confirmed liver safety

Boehringer Ingelheim today announced very positive results from their landmark RE-COVER™ study – the most advanced trial programme assessing a novel oral anticoagulant in development for acute venous thromboemolism (VTE) treatment – presented at the American Society of Hematology Annual Meeting¹ and published in the New England Journal of Medicine online.

The oral direct thrombin inhibitor, dabigatran etexilate (150 mg twice-daily, BID), showed equal efficacy compared to well-controlled warfarin at preventing recurrent VTE (2.4% vs. 2.1%, hazard ratio 1.10, 95% CI 0.65 to 1.84, p<0.001 for prespecified non-inferiority margin). For safety, dabigatran etexilate demonstrated a significant 37% reduction in major or clinically relevant non-major bleeding (p=0.002). Major bleeding was comparable between dabigatran etexilate (20 patients, 1.6%) and warfarin (24 patients, 1.9%). For any bleeds, dabigatran etexilate showed a significant 29% reduction (p=0.0002) compared to warfarin. These outstanding results were achieved without any evidence of liver problems.¹

“The results of RE-COVER™ are a long-awaited breakthrough in the treatment of VTE; not only does dabigatran etexilate offer an effective therapy to prevent recurrent VTE it does so with less bleeding than warfarin.” commented Dr Sam Schulman, Principal Investigator, Department of Medicine, McMaster University, Hamilton, Canada. “Warfarin is a highly effective therapy when well-controlled within its narrow therapeutic range, as in clinical trials, but in the real world sufficient control is rarely achieved and maintained, leaving patients poorly protected from VTE or at risk of bleeding. With dabigatran, we have a therapy that protects our patients effectively and safely, without need for frequent laboratory monitoring and dose changes.”

VTE – which includes deep vein thrombosis (DVT) and its potentially fatal acute complication pulmonary embolism (PE) – is the third most common cardiovascular disease worldwide (after coronary heart disease and stroke).² VTE affects around 1.5 million Europeans³ and 3 million Americans⁴ each year and kills more than double the number of people than AIDS, breast cancer, prostate cancer and traffic accidents combined in Europe.³

Earlier this year, the RE-LY® study (18,113 patients in 44 countries worldwide) showed groundbreaking results for dabigatran etexilate convincingly beating warfarin in stroke prevention in atrial fibrillation.⁵

“The results of the RE-COVER™ trial are very encouraging news for VTE patients,” said Eve Knight, Chief Executive of the patient organisation AntiCoagulation Europe. “Although warfarin is an effective treatment it imposes many restrictions on patients’ lives as they require regular blood tests, dose adjustments and have limitations placed on the food and drink they can consume. In addition, the unpredictability of warfarin places patients at risk of recurrent clots or increased bleeding if it is not sufficiently monitored. AntiCoagulation Europe therefore welcomes the news that dabigatran may offer a safer, more simple alternative to warfarin for the treatment of potentially life-threatening blood clots.” Current guidelines recommend treating acute VTE with anticoagulants to prevent new blood clots from forming and old ones from getting any bigger, as well as reducing the risk of both post thrombotic syndrome and thromboembolic pulmonary hypertension. These chronic diseases can cause substantial illness and a high economic burden.^6,7 Current standard treatment involves the short-term use of a low molecular weight heparin for therapy initiation in hospital with subsequent continuation of treatment with a vitamin K antagonist (VKA, such as warfarin).⁸ This provides a three-fold reduction in recurrence of VTE and extended duration of therapy reduces this risk by 50%.^9,10

While VKAs are highly effective anticoagulants, they have multiple limitations which make maintaining patients within the narrow therapeutic INR range of 2.0-3.0 challenging, requiring frequent monitoring to ensure patient safety and efficacy. Even with close monitoring, as in a clinical trial, patients only spend half their time within this range and this tends to be even lower in the ‘real-world setting’.¹¹ Outside of the narrow range, the rate of bleeding is 44% and the rate of clotting is 48%.¹²

Dabigatran etexilate provides effective, predictable and consistent anticoagulation with a low potential for drug interactions and no food interactions, without the need for routine coagulation monitoring or dose adjustment. In contrast to VKAs, which variably act via different coagulation factors, direct thrombin inhibitors achieve potent anthrombotic effects by specifically blocking the activity of thrombin (both free and clot-bound), the central enzyme in the process responsible for clot (thrombus) formation.

In total, four trials involving 8,900 patients are exploring dabigatran etexilate in VTE treatment: RE-COVER™ and RE-COVER™II in acute VTE and RE-MEDY™ and RE-SONATE™ in prevention of secondary VTE. The results of RE-COVER™ and the very favourable results of RE-LY⁵ add to the growing database of evidence supporting the efficacy and safety of dabigatran etexilate across a wide range of acute and chronic thromboembolic disorders from the RE-VOLUTION® clinical development programme involving over 38,000 patients.

“Following the outstanding results from the RE-LY® trial, these impressive new data mean dabigatran etexilate has the potential to benefit even more patients and overtake warfarin as the treatment of choice”, commented Dr Andreas Barner, the chairman of the Board of Managing Directors of Boehringer Ingelheim. “We look forward to submitting these results to the regulatory authorities so that the results of this landmark trial can be put into a real world setting.”

For further information, including editors notes and references, please visit http://www.boehringer-ingelheim.com/news/news_releases/press_releases/2009/06_december_2009.html

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About Boehringer Ingelheim

The Boehringer Ingelheim group is one of the worlds 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 138 affiliates in 47 countries and 41,300 employees. Since it was founded in 1885, the independent, 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 11.6 billion euro while spending one fifth of net sales in its largest business segment Prescription Medicines on research and development.

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