Rivaroxaban Significantly Reduces Risk of Stroke in Patients with Atrial
Fibrillation with Comparable Safety versus Warfarin in Pivotal Phase III
Study

• ROCKET AF shows superiority of once-daily rivaroxaban over warfarin in protecting AF patients from stroke and non-CNS systemic embolism
• Rivaroxaban demonstrates comparable major and non-major clinically relevant bleeding, as well as significantly lower rates of intracranial hemorrhage vs. warfarin
• ROCKET AF is the seventh Phase III clinical trial with rivaroxaban to show consistently improved outcomes for rivaroxaban compared to standard of care

TORONTO, Nov. 15 /CNW/ - Bayer today announced the results from the pivotal, double-blind Phase III, ROCKET AF trial. In the study, rivaroxaban demonstrated superiority to warfarin in reducing the risk of stroke and non-CNS systemic embolism in patients with atrial fibrillation (AF). Importantly, rates of bleeding were similar to warfarin, and bleeding events most concerning to physicians and patients, including intracranial hemorrhage, critical organ bleed, and bleeding-related death, were significantly lower in the rivaroxaban group. The results were presented today as a late-breaker at the American Heart Association Scientific Sessions 2010 in Chicago, USA.

"Atrial fibrillation and stroke devastate the lives of millions of patients and their families worldwide every year. Anticoagulation with warfarin is effective in preventing strokes in patients with atrial fibrillation and has been the standard of care for more than half a century. However, its use in clinical practice is associated with many limitations", said Professor Werner Hacke, Chair of the Department of Neurology at the University of Heidelberg, Germany, and member of the ROCKET AF Executive Steering Committee. "The ROCKET AF study has shown that once-daily rivaroxaban promises patients improved protection from stroke, with good safety and added convenience."

With 14,264 patients randomized, ROCKET AF is the largest double-blind study undertaken in the prevention of stroke in patients with AF, comparing once-daily rivaroxaban to dose-adjusted warfarin. For the primary efficacy endpoint, rivaroxaban was superior to warfarin, delivering a 21% relative risk reduction in stroke and non-CNS systemic embolism in the pre-specified on treatment population (1.70% vs. 2.15%, p=0.015). Additionally, in the intent to treat (ITT) population which followed all patients randomised in the trial until its completion, whether or not they completed the full course of therapy or switched to other options, rivaroxaban showed comparable benefits to warfarin (2.12% vs. 2.42%, p<0.001 for non-inferiority). This result indicates that the treatment benefits compared to warfarin were sustained as long as the patients received rivaroxaban.

In addition, significantly fewer cases of hemorrhagic stroke, one of the most severe types of stroke, were observed in patients on rivaroxaban (0.26% vs. 0.44% p=0.024). Compared to warfarin, rivaroxaban also showed numerically fewer cases of myocardial infarction (0.91% vs. 1.12%, p=0.121), and an observed reduction in rates of all-cause mortality (1.87% vs. 2.21%, p=0.073).

The improved protection of patients provided by rivaroxaban in ROCKET AF was not associated with an increase in bleeding. On the principal safety measure of major and non-major clinically relevant bleeding events, rivaroxaban was similar compared with warfarin (14.91% vs. 14.52%, p=0.442). Rates of major bleeding were also comparable between rivaroxaban and warfarin (3.60% vs. 3.45%, p=0.576). Importantly, patients treated with rivaroxaban had fewer intracranial hemorrhages (0.49% vs. 0.74%, p=0.019), fewer critical organ bleeds (0.82% vs. 1.18%, p=0.007) and lower bleeding-related deaths (0.24% vs. 0.48%, p=0.003) than those on warfarin. Rates of hemoglobin drop (2.77% vs. 2.26%, p=0.019) and transfusion requirements (1.65% vs. 1.32%, p=0.044) were increased when compared to patients who received warfarin.

The frequency of abnormal laboratory values of liver function was balanced between the treatment groups and there was no signal for serious liver damage attributable to rivaroxaban observed in the trial.

Rivaroxaban was well tolerated in the study, and rates of discontinuation due to adverse events were similar to those seen for patients on warfarin. Rivaroxaban, administered once daily, without the need for routine laboratory coagulation monitoring delivered improved protection, simplified dosing and good tolerability.

"Given the prevalence and morbidity associated with atrial fibrillation, and the well-known difficulties with warfarin use, it is exciting to have an alternative which was documented in this study to be effective with no increase in significant bleeding," said Robert M. Califf, M.D., study co-chairman and Vice Chancellor for Clinical Research from Duke University.

About Atrial Fibrillation

AF is the most common sustained cardiac rhythm disorder and affects approximately 250,000 people in Canada and up to six million people in Europe. In patients with AF, the irregular heartbeat makes them vulnerable to the formation of a blood clot in the atria, which can travel to the brain, potentially resulting in a stroke. Strokes cause damage to the brain, and can lead to physical and behavioral impairment, or even death. People with AF are at a five-fold increased risk for stroke compared with the general population - about one-third of them will suffer from a stroke.

About ROCKET AF

ROCKET AF (Rivaroxaban Once daily oral direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) was a prospective, randomized, double-blind, double-dummy parallel group outcomes study comparing once-daily rivaroxaban (20 mg, or 15 mg for patients with moderate renal impairment) with dose-adjusted warfarin in 14,264 patients with non-valvular atrial fibrillation who were at risk for stroke or non-CNS systemic embolism.

This was an event-driven trial, which ended when the pre-specified number of efficacy events was accumulated. The primary objective of ROCKET AF was to demonstrate the efficacy of once-daily rivaroxaban as non-inferior to well controlled warfarin in the prevention of stroke and non-CNS systemic embolism in patients with non-valvular AF. The principal safety measure of ROCKET AF was the composite of major plus non-major clinically relevant bleeding events. The patients with AF evaluated in ROCKET AF typify those who are treated today by physicians with an anticoagulant to help reduce the risk of stroke.

About XARELTO® (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, 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 an extensively studied oral, direct Factor Xa inhibitor. More than 65,000 patients are participating in the XARELTO clinical development program, evaluating 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 CropScience 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.

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