New Sub-analysis Data Highlights the Benefit of LIXIANA®▼ (edoxaban) Over Warfarin in NVAF Patients According to More Comprehensive Stroke Risk Scoring

MUNICH, August 29, 2017 /PRNewswire/ --

• Sub-analysis highlights the protective effect of edoxaban against stroke or systemic embolic events (SEEs) and its superior safety in terms of major bleeding risk compared to warfarin, in non-valvular atrial fibrillation (NVAF) patients at varying levels of stroke risk.^[1]
• The data is being presented at ESC Congress 2017, in Barcelona, Spain.   

Daiichi Sankyo Europe GmbH (hereafter, Daiichi Sankyo) today announced new sub-analysis data, demonstrating that LIXIANA^® (edoxaban) provides comparable efficacy and greater safety compared to warfarin, across NVAF patients with different stroke risk scores. The findings are based on a sub-analysis of the Effective aNticoaGulation with factor XA next GEneration in Atrial Fibrillation (ENGAGE AF-TIMI 48) clinical study, and provide more specific insights into the use of oral, once-daily direct factor Xa-inhibitor edoxaban compared to warfarin in NVAF patients grouped by stroke risk (as measured by CHA₂DS₂-VASc score).^[1] The results of the study are being presented at ESC Congress 2017 in Barcelona, Spain.

The ENGAGE AF-TIMI 48 study has previously shown that once-daily edoxaban is as effective as warfarin for the prevention of stroke or SEEs, while significantly reducing the risk of bleeding. This new sub-analysis has established that the benefit of edoxaban over warfarin is maintained, with no significant effect modification by CHA₂DS₂-VASc score, which assesses stroke risk more accurately than the previously used CHADS₂ score.^[1],[2]

Providing insights into edoxaban's risk-benefit profile in stroke prevention, the sub-analysis shows that edoxaban provides an incremental absolute reduction in safety events (including major bleeding, intracranial haemorrhage and cardiovascular hospitalisations) for NVAF patients, over those receiving warfarin, as the risk of stroke increases.^[1] While overall results from ENGAGE AF-TIMI 48 demonstrate that edoxaban provides superior safety for NVAF patients in terms of major bleeding risk compared to warfarin,^[2] this data further shows that the safety benefit remains in place in patients with higher CHA₂DS₂-VASc scores (p-int=0.99 for major bleeding).^[1] Major bleeding is a key consideration in assessing appropriate treatment in NVAF, and as such, this data highlights the value of edoxaban for patients at varying levels of stroke risk.^[1]

Joris De Groot, MD, PhD, Cardiologist, University of Amsterdam and lead author of the study, commented: "These findings can greatly benefit physicians in clinical practice. Reducing stroke risk is paramount to effective NVAF management. The availability of data regarding the use of edoxaban in NVAF patients of varying levels of stroke risk will help better inform treatment decisions and support treatment assurance for physicians and patients."

The sub-analysis shows that edoxaban provides effective protection against stroke and SEEs, even in patients at high stroke risk.^[1] The efficacy of edoxaban compared to warfarin for the prevention of stroke and SEEs is maintained among patients with different CHA₂DS₂-VASc scores (p-int=0.546 for stroke and SEEs).^[1]

"We are pleased that this new sub-analysis of ENGAGE AF-TIMI 48 shows the benefit of edoxaban in AF patients of varying stroke risk," stated Wolfgang Zierhut, MD, Executive Director, EU Cardiovascular Medical Affairs. "Daiichi Sankyo is committed to advancing and expanding research in this important disease area and to supporting both physicians and patients, including patients in high-risk groups."

Findings from the ENGAGE AF-TIMI 48 clinical trial and the sub-analysis, further support the 2016 update to the ESC Guidelines for the management of atrial fibrillation, which recommend non-vitamin K oral anticoagulants (NOACs) as broadly preferable to vitamin K antagonists (VKAs) such as warfarin for stroke prevention in NVAF patients, noting the reduced risk of bleeding with NOACs.^[3]

ENGAGE AF-TIMI 48 is a global phase 3 clinical trial which randomised 21,105 patients with non-valvular AF to a once-daily warfarin regimen, a higher-dose edoxaban regimen (HDER, 60 or 30 mg once-daily) or a lower-dose edoxaban regimen (LDER, 30 or 15 mg once-daily). In this sub-analysis of HDER, patients were grouped by CHA₂DS₂-VASc score (≤2, 3, 4, 5, ≥6); and efficacy (stroke and SEEs), safety (major bleeding), intracranial haemorrhage and cardiovascular hospitalisation outcomes were compared in patients receiving HDER and those receiving warfarin.^[1]

About the ENGAGE AF-TIMI 48 Study   

ENGAGE AF-TIMI 48 (Effective aNticoaGulation with factor xA next GEneration in Atrial Fibrillation) was a three-arm, randomised, double-blind, double-dummy, global phase 3 clinical trial comparing once-daily edoxaban with warfarin in 21,105 patients with NVAF at moderate-to-high risk of thromboembolic events at 1,393 centres in 46 countries. ENGAGE AF-TIMI 48 compared two edoxaban treatment strategies, a higher dose arm (60 mg or 30 mg dose reduced) once-daily and a lower dose arm (30 mg or 15 mg dose reduced) once-daily, with warfarin in patients with NVAF for a median of 2.8 years. Patients were dose reduced for creatinine clearance (CrCL) 30 to 50 mL/min, body weight of 60 kg or less or certain p-glycoprotein inhibitor use. ENGAGE AF-TIMI 48 represents the largest and longest single comparative global trial with a novel anticoagulant in patients with NVAF performed to date.^[2] The full results were presented at the AHA Scientific Sessions 2013 in Dallas and published in the New England Journal of Medicine.

About Edoxaban   

Edoxaban is an oral, once-daily, direct factor Xa (pronounced "Ten A") inhibitor. Factor Xa is one of the key components responsible for blood clotting, so inhibiting this makes the blood thin and less prone to clotting. Edoxaban is currently marketed by Daiichi Sankyo and its partners in more than 20 countries around the world.

The edoxaban Summary of Product Characteristics can be viewed here: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002629/WC500189045.pdf

About Edoxaban Clinical Research Programme (ECRP)   

Daiichi Sankyo is committed to expanding scientific knowledge about edoxaban, as demonstrated through our research programmes evaluating its use in a broad range of cardiovascular conditions, patient types and clinical settings in atrial fibrillation (AF) and venous thromboembolism (VTE). The Edoxaban Clinical Research Programme includes multiple RCTs (randomised, controlled trials), registries and non-interventional studies, with the goal of generating new clinical and real-world-data regarding its use in AF and VTE populations. Daiichi Sankyo expects that more than 100,000 patients will participate in the Edoxaban Clinical Research Programme, including completed, ongoing and future research.

The RCTs include:

• ENSURE-AF (EdoxabaN vs. warfarin in subjectS UndeRgoing cardiovErsion of Atrial Fibrillation), in AF patients undergoing electrical cardioversion
• ENTRUST-AF PCI (EdoxabaN TReatment versUS VKA in paTients with AF undergoing PCI), in AF patients undergoing percutaneous coronary intervention
• Hokusai-VTE Cancer (Edoxaban in Venous Thromboembolism Associated with Cancer), in patients with cancer and an acute VTE event
• ELDERCARE-AF (Edoxaban Low-Dose for EldeR CARE AF patients), in elderly AF patients in Japan
• ELIMINATE-AF (EvaLuatIon of edoxaban coMpared with VKA IN subjects undergoing cAThEter ablation of non-valvular Atrial Fibrillation)
• ENVISAGE-TAVI AF (EdoxabaN Versus standard of care and theIr effectS on clinical outcomes in pAtients havinG undergonE Transcatheter Aortic Valve Implantation (TAVI) - Atrial Fibrillation)

In addition, global and regional registry studies will provide important real-world data about the use of edoxaban and other oral anticoagulants in everyday practice, and include:

• ETNA-AF (Edoxaban Treatment in routiNe clinical prActice in patients with non valvular Atrial Fibrillation)
• ETNA-VTE (Edoxaban Treatment in routiNe clinical prActice in patients with Venous ThromboEmbolism)
• EMIT-AF/VTE (Edoxaban Management In diagnostic and Therapeutic procedures-AF/VTE)
• Prolongation PREFER in AF (PREvention oF thromboembolic events - European Registry) in patients with AF
• ANAFIE (All Nippon AF In Elderly) Registry in Japan
• Cancer-VTE Registry in Japan

We are committed to adding to the scientific body of knowledge around edoxaban in a variety of AF and VTE patients, including those who are vulnerable.

About Daiichi Sankyo    

Daiichi Sankyo Group is dedicated to the creation and supply of innovative pharmaceutical products to address diversified, unmet medical needs of patients in both mature and emerging markets. With over 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 15,000 employees around the world draw upon a rich legacy of innovation and a robust pipeline of promising new medicines to help people. In addition to a strong portfolio of medicines for hypertension and thrombotic disorders, under the Group's 2025 Vision to become a "Global Pharma Innovator with Competitive Advantage in Oncology," Daiichi Sankyo research and development is primarily focused on bringing forth novel therapies in oncology, including immuno-oncology, with additional focus on new horizon areas, such as pain management, neurodegenerative diseases, heart and kidney diseases, and other rare diseases. For more information, please visit: http://www.daiichisankyo.com.

Forward-looking statements    

This press release contains forward-looking statements and information about future developments in the sector, and the legal and business conditions of DAIICHI SANKYO Co., Ltd. Such forward-looking statements are uncertain and are subject at all times to the risks of change, particularly to the usual risks faced by a global pharmaceutical company, including the impact of the prices for products and raw materials, medication safety, changes in exchange rates, government regulations, employee relations, taxes, political instability and terrorism as well as the results of independent demands and governmental inquiries that affect the affairs of the company. All forward-looking statements contained in this release hold true as of the date of publication. They do not represent any guarantee of future performance. Actual events and developments could differ materially from the forward-looking statements that are explicitly expressed or implied in these statements. DAIICHI SANKYO Co., Ltd. assume no responsibility for the updating of such forward-looking statements about future developments of the sector, legal and business conditions and the company.

References   

Contact
Lydia Worms (Europe)
Daiichi Sankyo Europe GmbH
Edoxaban Communications & Product PR Europe
+49(89)7808751

EDX/17/0189
August 2017