Bayer Forms Collaboration With Academic and Governmental Institutions for Global Phase III Study to Evaluate Xarelto®▼(rivaroxaban) in Patients With a Recent Embolic Stroke of Undetermined Source

NEWBURY, England, January 27, 2015 /PRNewswire/ --

PRESS RELEASE FOR UK TRADE MEDIA ONLY 

In addition, Xarelto^®▼(rivaroxaban) label now includes guidance for use in patients with atrial fibrillation undergoing cardioversion

Bayer HealthCare today announces a collaboration with the Population Health Research Institute (PHRI) and the Canadian Stroke Prevention Intervention Network (C-SPIN) to conduct the global Phase III, indication seeking trial, NAVIGATE ESUS, which will investigate the benefits of the once-daily, oral Factor Xa Inhibitor ('xaban'), rivaroxaban in patients with Embolic Stroke of Undetermined Source (ESUS) or cryptogenic stroke. Enrollment of patients for the study has started successfully.

Approximately 32,000 people each year suffer from ESUS in the UK, for which there is limited knowledge available to guide treatment decisions.^[1],[2] NAVIGATE ESUS will include approximately 7,000 patients and be conducted in more than 25 countries.  

"We are committed to investigating the potential further benefits for rivaroxaban in areas where there is a significant unmet need. The ROCKET AF study confirmed that once-daily rivaroxaban is highly effective in preventing stroke in patients with non-valvular atrial fibrillation, with and without previous stroke or transient ischaemic attack, so we believe there is potential for rivaroxaban to provide this same protective benefit to patients with a recent ESUS," said Dr Luis Felipe Graterol, Medical Director, Bayer HealthCare UK.

The extensive evaluation of rivaroxaban to protect different patient populations at risk of venous and arterial thromboembolism makes it the most studied direct oral Factor Xa Inhibitor ('xaban') in the world. Rivaroxaban is already approved for five indications in seven areas of use and its investigation - both completed and ongoing - will include more than 275,000 patients in clinical trials and real world settings.

Most recently, Bayer HealthCare announced an update to the rivaroxaban prescribing information to include use in treating patients with non-valvular atrial fibrillation (AF) undergoing cardioversion. This label update provides physicians with important information on the practical use of rivaroxaban in patients with AF who require cardioversion.

"Ensuring patients are adequately anticoagulated when they undergo cardioversion is crucial. International normalised ratio (INR) levels for patients treated with warfarin can be inconsistent and/or out of therapeutic range. This problem is eliminated by the fixed-dose anticoagulation provided by Xarelto. The Xarelto label update is extremely welcome, providing physicians with clear guidance for treating patients with atrial fibrillation undergoing cardioversion," said Dr Oliver Segal, Consultant Cardiac Electrophysiologist, The Heart Hospital, UCLH.

The label update is based on findings from the X-VeRT study, the first completed prospective trial of any novel oral anticoagulant (NOAC), in 1,504 patients undergoing elective cardioversion.^[3] In this exploratory study, rivaroxaban demonstrated effective protection with an event rate comparable to Vitamin K Antagonists (VKA) in the primary efficacy endpoint - composite of all stroke, transient ischaemic attack, peripheral embolism, myocardial infarction and cardiovascular death (0.5% vs. 1.0%; risk ratio: 0.50; 95% confidence interval: 0.15-1.73). In the primary safety endpoint of major bleeding, rivaroxaban demonstrated a comparable safety profile with no increase vs. VKA (0.6% vs. 0.8%; risk reduction 0.76; 95% confidence interval: 0.21-2.67) in the incidence of major risk ratio (relative risk reduction of 24%, ARR 0.19). The practical advantage of using rivaroxaban was demonstrated by the shorter time frame to cardioversion compared with treatment using warfarin in the delayed cardioversion group (median of 22 days vs. 30 days respectively, p<0.001). The study was published in the European Heart Journal in September 2014.^[3]

About NAVIGATE ESUS 

NAVIGATE ESUS is a randomised double-blind, event-driven superiority Phase III study of secondary prevention of stroke and prevention of systemic embolism in patients with a recent embolic stroke of undetermined source (ESUS). The study will include approximately 7,000 patients from 350 sites, across more than 25 countries worldwide. The primary efficacy outcome is the composite of the first occurrence of all recurrent strokes (ischaemic, hemorrhagic, and undefined stroke, and transient ischaemic attack (TIA) with positive neuroimaging) and systemic embolism. The primary safety outcome is modified ISTH major bleeding. Patients will be randomised to receive either rivaroxaban 15mg once daily or acetylsalicylic acid (ASA) 100mg once daily.

About the X-VeRT Study^[3]

X-VeRT was a prospective, randomised, open-label, parallel group Phase IIIb study involving 1,504 patients with hemodynamically stable non-valvular AF of > 48 hours or unknown duration, recruited from 16 countries worldwide. Anticoagulation naïve or experienced patients scheduled for cardioversion were randomly assigned to rivaroxaban 20mg once-daily (15mg once-daily if creatinine clearance was between 30-49 mL/min) or INR-adjusted VKA therapy (target INR 2.0-3.0) in a 2:1 ratio. The decision regarding early cardioversion (a goal of between 1-5 days of rivaroxaban or usual VKA therapy before the procedure) or delayed cardioversion (rivaroxaban or VKA for 3-8 weeks prior to the procedure) was taken by the local investigator. AF patients on rivaroxaban demonstrated a numerically reduced risk of cardiovascular events of 50% (ARR 0.51) compared to VKA, as well as a reassuring bleeding profile with a numerically lower major bleeding incidence risk of 24% (ARR 0.19).

Overall, the mean time from randomisation to cardioversion was similar in patients assigned to rivaroxaban compared to those assigned to VKA treatment in the early cardioversion group: 1.8±1.6 days vs 2.1±3.0 days, P = 0.628); but was shorter with rivaroxaban in the delayed cardioversion group (24.6±5.6 days vs 33.7±13.1 days, P < 0.001). The positive rivaroxaban efficacy and safety outcomes findings were consistent in both early and delayed cardioversion strategies. These results were not statistically significant as the trial was not powered accordingly.

About Bayer HealthCare  

The Bayer Group is a global enterprise with core competencies in the fields of health care, agriculture and high-tech materials. Bayer HealthCare, a subgroup of Bayer AG with annual sales of EUR 18.9 billion (2013), 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, develop, manufacture and market products that will improve human and animal health worldwide. Bayer HealthCare has a global workforce of 56,000 employees (Dec 31, 2013) 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. These factors include those discussed in Bayer's public reports which are available on the Bayer website at http://www.bayer.com . The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

References 

1. Hart RG, Diener HC, Coutts SB, et al. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurology. 2014 Apr;13(4):429-38

2. Stroke of the Nation Stroke Statistics 2015. http://www.stroke.org.uk/sites/default/files/State%20of%20the%20Nation_2015_0.pdf . Last accessed January 2015

3. Cappato R, Ezekowitz MD, Klein AL, et al. Rivaroxaban vs. vitamin K antagonists for cardioversion in atrial fibrillation. Eur Heart J 2014; doi:10.1093/eurheartj/ehu367

L.GB.01.2015.9458
Date of preparation: January 2015

Media contacts: Hayley Knight, Bayer UK, Tel. +44 (0)1635 563522, Mobile: +44 (0)7788 365 833, E- Mail: hayley.knight@bayer.com; Hannah Macgregor, Tonic Life Communications, Tel. +44 (0)20 7798 9904, Mobile: +44 (0)7817 227 954, E-Mail: hannah.macgregor@toniclc.com