Study shows XARELTO(R) (rivaroxaban) offers net clinical benefit for the
treatment of deep vein thrombosis compared to current standard of care

The EINSTEIN-DVT study reinforces that XARELTO is a simple and convenient treatment option for clinicians and patients alike

TORONTO, Sept. 1 /CNW/ - Bayer HealthCare Pharmaceuticals today announced that XARELTO(R) (rivaroxaban), a novel anti-clotting therapy, achieved improvement in net clinical benefit in a study looking at treatment of patients with deep vein thrombosis (DVT). DVT is the formation of a blood clot in a deep vein, usually in the legs, that partially or totally blocks the flow of blood. It is estimated that DVT affects 45,000 Canadians per year(1). Around one-third of patients with DVT will progress to having a potentially fatal pulmonary embolism (PE)(2), where the blood clot breaks apart and travels to the lungs, ultimately blocking a blood vessel there. Even in the absence of a PE, DVT alone can have burdensome and costly consequences such as post-thrombotic syndrome and an increased risk of recurring blood clots. Therefore, achieving treatment goals is essential. XARELTO prevents the formation and minimizes the risk of these potentially-deadly blood clots.(3)

"Results from this study could change the way doctors treat deep vein thrombosis," says Dr. Alexander G. G. Turpie, Professor of Medicine at the Michael G. DeGroote School of Medicine at McMaster University, Hamilton, ON. "A single-drug approach such as XARELTO could potentially provide an effective and well-tolerated DVT treatment for clinicians to prescribe, as well as a convenient, fixed-dose regimen for patients to use."

In the study, called EINSTEIN-DVT and presented this week during the European Society of Cardiology (ESC) Congress, net clinical benefit, a pre-specified secondary outcome defined as the composite of the primary efficacy outcome plus major bleeding, was shown as an improvement for oral rivaroxaban compared to standard therapy (2.9% vs. 4.2%, respectively; HR of 0.67, CI: 0.47 - 0.95). The benefit demonstrated by EINSTEIN-DVT means that clinicians and patients could potentially move from two-drug therapy to single-drug therapy, with no need for injections.

Rivaroxaban demonstrated non-inferiority for the primary efficacy outcome, defined as the cumulative incidence of symptomatic recurrent DVT and non-fatal or fatal PE, in patients with acute symptomatic DVT compared with the current standard of care of enoxaparin followed by a vitamin K antagonist, (2.1% vs. 3.0%, respectively (p (less than)0.0001 for non-inferiority)). Rivaroxaban demonstrated similar results compared to the standard of care for the principal safety outcome, a composite of major or non-major clinically relevant bleeding events (8.1% in both treatment groups, (p=0.77)). Monthly liver function tests did not reveal a signal for impaired liver safety. Rivaroxaban was well tolerated in the study, and discontinuation rates related to adverse events were low and similar in both treatment groups.

XARELTO is currently indicated in Canada for the prevention of venous thromboembolic events (VTE) in patients who have undergone elective total hip replacement or total knee replacement surgery(4).

About the EINSTEIN Clinical Trial Program

EINSTEIN is a global clinical development program composed of three clinical studies (EINSTEIN-DVT, EINSTEIN-PE and EINSTEIN-Extension) evaluating rivaroxaban in the treatment of patients with acute symptomatic DVT or PE for the prevention of recurrent venous thromboembolic events. This Phase III clinical development program of three trials includes more than 8,000 patients in centres around the world.

Two of these studies enrolled patients with acute, symptomatic deep vein thrombosis (EINSTEIN-DVT) or pulmonary embolism (EINSTEIN-PE). In these two trials, patients received oral rivaroxaban 15 mg twice-daily for the first three weeks, followed by oral rivaroxaban 20 mg once-daily, compared with initial enoxaparin treatment followed by a vitamin K antagonist.

The multinational Phase III EINSTEIN-DVT study investigated a new single-drug approach with rivaroxaban compared with standard therapy in a randomized, open-label, assessor-blind, non-inferiority study involving more than 3,400 patients with acute symptomatic DVT, but without any symptoms of PE. Standard therapy for venous thromboembolism, including DVT, currently includes two compounds: low molecular weight heparin administered by subcutaneous injection, followed by a vitamin K antagonist, which requires regular monitoring of the prothrombin time, reported as the International Normalized Ratio, for safety.

The third study, EINSTEIN-Extension, compared the efficacy and safety of rivaroxaban to placebo in the secondary prevention of recurrent symptomatic venous blood clots by extending preventative treatment by an additional 6 or 12 months beyond a previously completed treatment regimen of 6 or 12 months of therapy, and enrolled approximately 1,200 patients with symptomatic DVT or PE. The data demonstrated that oral rivaroxaban 20 mg once-daily significantly reduced the risk of recurrent symptomatic VTE by 82% compared to placebo in patients who had been treated for a previous DVT or PE. The rate of major bleeding was low.

About XARELTO(R) (rivaroxaban)

XARELTO is a novel oral anti-clotting therapy that prevents the formation and minimizes the risk of potentially-deadly blood clots. It has a rapid onset of action with a predictable dose response and high bioavailability, no requirement for routine coagulation monitoring, as well as a limited potential for food and drug interactions. Its fixed-dose regimen provides improved effectiveness and outcomes compared to the current standard of care.

XARELTO is approved in more than 100 countries worldwide and has been successfully launched in more than 75 countries, achieving the market leader position among the new oral anticoagulants. In Canada, XARELTO is currently indicated for the prevention of VTE events in patients who have undergone elective total hip replacement or total knee replacement surgery(5), and is the only new oral anticoagulant that has consistently demonstrated superior efficacy over enoxaparin for this indication.

The extensive clinical trial program supporting XARELTO makes it the most studied oral, direct Factor Xa inhibitor in the world today. More than 65,000 patients are participating in the XARELTO clinical development program, which will evaluate the product in the prevention and treatment of a broad range of acute and chronic blood-clotting disorders, including stroke prevention in patients with atrial fibrillation, secondary prevention of acute coronary syndrome, and VTE prevention in hospitalized, medically ill patients.

About Bayer Inc.

Bayer Inc. (Bayer) is a Canadian subsidiary of Bayer AG, an international research-based group with core businesses in health care, crop science and innovative materials. Headquartered in Toronto, Ontario, Bayer Inc. operates the Bayer Group's HealthCare and MaterialScience businesses in Canada. Bayer Crop Science Inc., headquartered in Calgary, Alberta operates as a separate legal entity in Canada. Together, the companies play a vital role in improving the quality of life for Canadians - producing products that fight diseases, protecting crops and animals, and developing high-performance materials for applications in numerous areas of daily life. Canadian Bayer facilities include the Toronto headquarters and offices in Montréal and Calgary.

Bayer Inc. has approximately 800 employees across Canada and had sales of $853 million CDN in 2009. Globally, the Bayer Group had sales of over 31 billion Euro in 2009. Bayer Inc. invested approximately $50 million CDN in research and development in 2009. Worldwide, the Bayer Group spent the equivalent of over 2.7 billion Euro in 2009 in R&D. For more information, go to www.bayer.ca.

Forward-Looking Statements

This news release may contain forward-looking statements based on current assumptions and forecasts made by Bayer Group or subgroup management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer's public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

    
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    (1) Douketis, J. Treatment of deep vein thrombosis Canadian Family
        Physician, February 2005, Vol. 51.
    (2) White RH. The epidemiology of venous thromboembolism. Circul.
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    (3) Perzborn E. In vitro and in vivo studies of the novel antithrombotic
        agent BAY 59-7939 - an oral, direct Factor Xa inhibitor. J Thromb
        Haemost 2005; 3: 514-21.
    (4) Product Monograph Xarelto (rivaroxaban tablet), page 3.
    (5) Product Monograph Xarelto (rivaroxaban tablet), page 3.
    

For further information: Stephanie Fitch, Fleishman-Hillard Canada Inc., [phone]/[phone], [email protected]; Tiana DiMichele, Bayer Inc., [phone]/[phone], [email protected]