Bayer's Xarelto® (rivaroxaban) Becomes First Fixed Dose Once-Daily Anticoagulant Tablet Approved in the UK for Stroke Prevention in non-valvular Atrial Fibrillation; and the First Single Drug Regimen for Deep Vein Thrombosis

NEWBURY, England, December 19, 2011 /PRNewswire/ --

• First once-daily, fixed-dose preventative treatment for UK patients with non-valvular atrial fibrillation (an irregular heartbeat) at risk of the devastating consequences of stroke
• Xarelto offers a convenient, cost-effective, single drug solution for the treatment of deep vein thrombosis (DVT) without the need for regular injections
• Xarelto is now approved in the UK for the prevention and treatment of three blood clotting conditions, offering an effective therapy without the need for regular blood monitoring

Bayer HealthCare's oral anticoagulant tablet Xarelto® (rivaroxaban) has been approved for use in the United Kingdom in two important blood-clotting disorders:

• Prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation (AF), often referred to as an irregular heartbeat, who have one or more risk factors
• Treatment of deep vein thrombosis (DVT) and prevention of subsequent DVTs and pulmonary embolism (PE) following an acute DVT in adult patients

The approvals were granted this week by the European Commission following a close review of the drug's clinical trial data by the European Medicines Agency (EMA). Rivaroxaban is already licensed for the prevention of venous blood clots in patients undergoing hip or knee replacement surgery and has treated over 1 million patients worldwide in this indication, including over 100,000 patients in the UK alone^[1].

"The consequences of blood clots can be overwhelming and their prevention and treatment should rightly be considered a health priority," said Trudie Lobban MBE, Chief Executive and Founder of the Atrial Fibrillation Association. "Thrombosis represents a massive burden on patients and the UK health system. Warfarin eligible AF patients, especially those with a higher risk profile and with significant co-morbidities, tend to require more frequent INR testing. These additional tests have a significant impact on these patients' quality of life as well as on NHS resources, so the approval of new therapies to prevent stroke in atrial fibrillation are welcome."

Xarelto is the first in a class of drugs known as Factor Xa (ten-A) inhibitors, which act at a critical point in the blood-clotting (coagulation) process to prevent the formation of clots. The features of Factor Xa inhibitors include predictable effects, convenient oral dosing and a lower risk of drug-drug interactions as compared to VKA antagonists, meaning they do not require frequent dose adjustments or routine anticoagulation monitoring. Rivaroxaban will be made available at a fixed price of £2.10 per tablet. This provides the NHS with an effective and simple to use non Vitamin K antagonist (VKA) oral anticoagulant in the UK. For the majority of patients with AF a 20mg dose is appropriate, with a 15mg dose recommended in patients with reduced kidney function.

The most widely-prescribed drug in the UK for the prevention of stroke in patients with AF is warfarin. Warfarin is a highly effective stroke prevention therapy, but is subject to limitations including unpredictable anticoagulant effects which can cause difficulties in maintaining an appropriate therapeutic range, as well as a requirement for frequent routine coagulation monitoring. Additionally, for some patients warfarin can interact with numerous drugs and a wide array of food and drink.

The current standard of care for the treatment of DVT is the dual-drug approach of heparin, which acts quickly to provide an anti-clotting effect, followed by warfarin, which can take several days to begin working. Heparin requires administration by subcutaneous injection, which, although effective, can cause inconvenience, bruising and discomfort. Oral rivaroxaban provides a unique single drug solution, without the need for injections and has been shown to be effective and well-tolerated versus the dual-drug approach of heparin and warfarin. Like other similar anticoagulants (such as warfarin and heparin), rivaroxaban may cause bleeding.

"Xarelto represents a step forward in therapies to combat the consequences of blood clots which can be devastating for patients and their families," said Luis-Felipe Graterol, Medical Director at Bayer Healthcare UK. "There has been a long-established need for treatment options which don't require regular blood monitoring and avoid the potential limitations associated with both warfarin and injectable heparins."

Rivaroxaban is also indicated for the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery.

About AF

AF is the most common sustained cardiac rhythm disorder and affects approximately 750,000 people in the UK^[2]. People with AF are at a five-fold increased risk for stroke, and it is a major cause of the 150,000 strokes in the UK each year^[2,3]. An irregular heartbeat makes AF patients 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 behavioural impairment, or even death.

About DVT

DVT is the formation of a blood clot in a deep vein that partially or totally blocks the flow of blood. In the UK, it is estimated that one in every 1,000 people are affected by venous thrombosis each year^[4]. Of those, some have pre-existing risk factors including serious illness or major surgery (provoked DVT); however a number of patients will have no known pre-existing risk factors and can develop apparently spontaneous events (unprovoked DVT)^[4].

The majority of patients suffering from a venous blood clot will experience a DVT alone. However, DVT can progress to become a potentially fatal PE if 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 devastating and costly consequences such as post-thrombotic syndrome and an increased risk of recurring blood clots, and thus the achievement of treatment goals is critically important. The current treatment standard for DVT is the dual- drug approach of low molecular weight heparin administered by subcutaneous injection, with a VKA.

About Xarelto® (Rivaroxaban)

Rivaroxaban is an oral anticoagulant that was discovered in Bayer HealthCare's Pharmaceuticals' Wuppertal laboratories in Germany, and is being jointly developed by Bayer HealthCare Pharmaceuticals and Johnson & Johnson Pharmaceutical Research & Development, L.L.C. 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. Like other similar medicines (antithrombotic agents), rivaroxaban may cause bleeding which may potentially be life threatening.

Rivaroxaban is marketed under the brand name Xarelto® for VTE prevention in adult patients following elective hip or knee replacement surgery. Rivaroxaban is approved in more than 110 countries worldwide and to date has been successfully launched in more than 85 countries by Bayer HealthCare Pharmaceuticals in this indication. In the U.S., where rivaroxaban has been successfully launched in July 2011, Janssen Pharmaceuticals, Inc. (a Johnson & Johnson Company) holds marketing rights for rivaroxaban. The Bayer HealthCare Pharmaceuticals sales force is supporting the Janssen Pharmaceuticals, Inc. in designated hospital accounts.

The ROCKET AF study compared once daily rivaroxaban with dose adjusted warfarin in 14,264 patients with non-valvular AF who were at risk for stroke or non-CNS systemic embolism^[5]. In EINSTEIN DVT patients with acute DVT taking rivaroxaban 15mg twice daily for 3 weeks followed by 20mg were compared with initial enoxaparin treatment followed by warfarin^[6]. The ROCKET study demonstrated that rivaroxaban was non-inferior to warfarin in prevention of stroke in non valvular AF, and EINSTEIN showed that rivaroxaban was non-inferior to enoxaparin and warfarin in recurrence of symptomatic blood clots in patients with DVT. Rivaroxaban demonstrated a well tolerated safety profile in the studies^[5,6].

About Bayer HealthCare

The Bayer Group is a global enterprise with core competencies in the fields of health care nutrition and high-tech materials. Bayer HealthCare, a subgroup of Bayer AG with annual sales of more than EUR 16.913 billion (2010), is one of the world's leading, innovative companies in the healthcare and medical products industry and is based in Leverkusen, Germany. The company combines the global activities of the Animal Health, Consumer Care, Medical Care and Pharmaceuticals divisions. Bayer HealthCare's aim is to discover, manufacture and market products that will improve human and animal health worldwide. Bayer HealthCare has a global workforce of 55,700 employees and is represented in more than 100 countries.

Forward-Looking Statements

This 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. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

References

1. Bayer IMS Data on File, 2011.

2. Atrial Fibrillation, The Stroke Association, December 2010

3. The Stroke Association: Facts and Figures about Stroke: Available at: http://www.stroke.org.uk/media_centre/facts_and_figures/index.html. Last accessed: 9 December 2011

4. Venous Thrombosis: Lifeblood, the Thrombosis Charity, 2011

5. Patel, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N.Engl.J.Med 2011; 365 (10) 883-91

6. Bauersachs et al. Oral rivaroxaban for symptomatic venous thromboembolism. N.Engl.J.Med. 2010; 363 (26) 2499-2510

SOURCE Bayer UK