Daiichi Sankyo Presents First Snapshot Analyses from Global ETNA-AF Programme of Oral, Once-daily LIXIANA®? (edoxaban) in Patients with Nonvalvular Atrial Fibrillation in Routine Clinical Practice

MUNICH, Aug. 28, 2018 /PRNewswire/ --

• The Global ETNA-AF programme is a large and comprehensive single non-vitamin K oral anticoagulant (NOAC) repository of real-world data, as part of the Edoxaban Clinical Research Programme, EDOSURE
• Three snapshot analyses from baseline data add to growing evidence of the use of edoxaban in the real-world setting
• Data were presented during the ESC Congress 2018

Daiichi Sankyo Europe GmbH (hereafter, "Daiichi Sankyo") today announced results from three analyses of baseline data from patients in the Global ETNA-AF programme describing the use of oral, once-daily edoxaban (known by the brand name LIXIANA^®?) in routine clinical care. The data from 24,431 patients treated with edoxaban, representing 87% of total planned enrolled patients from more than 1,800 centers across 13 countries globally, highlight the broad range of cardiovascular risk factors and patient types being assessed to collect robust information on how edoxaban is being used in patients with nonvalvular atrial fibrillation (NVAF) in real-world settings. The data were presented at the ESC Congress 2018 in Munich.

"Daiichi Sankyo is committed to expanding scientific knowledge about edoxaban through ETNA-AF, which is part of EDOSURE, our robust clinical research programme comprised of more than 10 studies and more than 100,000 patients worldwide," said Hans Lanz, MD, Vice President, Head, Global Medical Affairs, Edoxaban. "The Global ETNA-AF programme will provide valuable information on edoxaban use, safety and effectiveness in a real-world setting that is being collected from these non-interventional studies. This will ultimately enable healthcare professionals to make best use of edoxaban in routine clinical practice."

The Global ETNA-AF programme combines information from non-interventional studies conducted in Europe, East Asia, and Japan, regarding the safety and effectiveness of edoxaban. The regional patient registries were designed to reflect regional needs and local clinical practice, and data were harmonised, transformed, and integrated into a single database. A total of more than 28,000 patients will be included in the Global ETNA-AF non-interventional studies and followed for two years (patients in Europe will be followed for four years). The Global ETNA programme will serve as a large and comprehensive single NOAC repository of real-world data on the use, effectiveness, and safety of patients with NVAF or venous thromboembolism (VTE).

The first snapshot analysis presented at ESC, which reported baseline demographics and patient characteristics in the Global ETNA-AF programme, showed that overall patients were older than those in the ENGAGE AF-TIMI 48 clinical trial of edoxaban but had fewer stroke risk factors and more often presented with paroxysmal NVAF.¹ The percentages of patients treated with edoxaban 60 mg once-daily and 30 mg once-daily in Europe were 76.7% and 23.3% respectively (N = 13,474).¹ The distribution of the edoxaban 60 mg and 30 mg QD dosing was largely consistent with the distribution in corresponding countries from ENGAGE AF-TIMI 48. Patient demographics were similar to ENGAGE AF-TIMI 48 in the European region.

The second analysis, which reported on baseline stroke and bleeding risks in the Global ETNA-AF programme, showed that across all regions, the population had a lower stroke risk and higher bleeding risk overall than those recorded in the corresponding countries in the ENGAGE AF-TIMI 48 trial.² Within non-interventional studies, physicians make clinical judgments to treat patients as appropriate. The EMA label requires only one risk factor for treatment and therefore differs from the inclusion criteria of ENGAGE AF-TIMI 48 that requires at least two major risk factors for enrolment. Global ETNA-AF enrolled a large proportion of high-risk patients including those with prior stroke, major bleed, intracranial hemorrhage, or CHA₂DS₂-VASc score ?4; these high-risk patients comprised 38.2% of patients enrolled from Europe.² In addition, the mean recalculated HAS-BLED score overall in Global ETNA-AF was 2.5 ± 1.13 (Europe: 2.6 ± 1.13).² In ENGAGE AF-TIMI 48, the mean HAS-BLED score in patients from countries corresponding to Global ETNA-AF was 1.8 ± 1.0.²

The third analysis, which reported on the use of antithrombotic therapy before initiation of edoxaban in the Global ETNA-AF programme, showed that more than two-thirds of patients treated with edoxaban were naïve to anticoagulant use before starting edoxaban (17,740, 72.6%).³ In Europe, 17.5% (2,364/13,474) were previously treated with a vitamin K antagonist (VKA) and 8.4% (1,138/13,474) were on another NOAC before starting edoxaban.³

"In comparison to corresponding countries in ENGAGE AF-TIMI 48, patients enrolled in Global ETNA-AF had lower stroke risk scores, and higher HAS-BLED scores," said Raffaele De Caterina, Professor of Cardiology and Director of the Cardiology Institute at G. d'Annunzio University, Chieti, Italy. "This may indicate a shift in the willingness of physicians to treat patients who have a higher bleeding risk, reflecting an evolution in the use of NOACs. Building on the results from ENGAGE AF-TIMI 48, which included patients with moderate to high risk of stroke, these data provide real-world evidence regarding the use of edoxaban for patients with low risk of stroke."

About ETNA-AF
ETNA-AF (Edoxaban Treatment in routiNe clinical prActice in patients with nonvalvular Atrial Fibrillation) is a non-interventional post-authorisation safety study (PASS) that combines data from distinct non-interventional studies in Europe, East Asia, and Japan in a single database. A total of more than 28,000 patients will be included in the ETNA-AF registries and followed for two years (patients in Europe will be followed for four years). The primary objective of ETNA-AF is to collect information on the real-world use of edoxaban in regional and country-specific routine clinical practice, including the safety and efficacy profile in non-preselected patients with non-valvular atrial fibrillation (NVAF).^4-8

About the ENGAGE AF-TIMI 48 Study
ENGAGE AF-TIMI 48 (Effective aNticoaGulation with factor xA next GEneration in Atrial Fibrillation) is 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, which is not currently approved, dose reduced) once-daily, with warfarin in patients with NVAF for a median of 2.8 years.⁹

About Atrial Fibrillation
AF is a condition where the heart beats irregularly and rapidly. When this happens, blood can pool and thicken in the chambers of the heart causing an increased risk of blood clots. These blood clots can break off and travel through the blood stream to the brain (or sometimes to another part of the body), where they have the potential to cause a stroke.¹⁰

AF is the most common type of heart rhythm disorder and is associated with substantial morbidity and mortality.¹¹ More than six million Europeans are diagnosed with AF, and this figure is expected to at least double over the next 50 years.^12,13 Compared to those without AF, people with the arrhythmia have a three to five times higher risk of stroke.¹⁴ One in five of all strokes are as a result of AF.¹²

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 in Japan, the U.S., South Korea, Hong Kong, Taiwan, Thailand, Canada, Brazil, Germany, the U.K., Switzerland, Ireland, the Netherlands, Italy, Spain, Belgium, Austria, Portugal, and other European countries.

About EDOSURE ? Edoxaban Clinical Research Programme

More than 10 studies, more than 100,000 patients worldwide
Daiichi Sankyo is committed to expanding scientific knowledge about edoxaban, as demonstrated through our research programs evaluating its use in a broad range of cardiovascular conditions, patient types and clinical settings in atrial fibrillation (AF) and venous thromboembolism (VTE) designed to further build on the results of the pivotal ENGAGE-AF and Hokusai-VTE studies. More than 100,000 patients worldwide are expected to participate in the edoxaban clinical research programme, EDOSURE, which is comprised of more than 10 RCTs (randomised, controlled trials), registries and non-interventional studies, including completed, ongoing and future research. The goal is to generate new clinical and real-world-data regarding edoxaban use in AF and VTE populations, providing physicians and patients worldwide with greater treatment assurance.

The RCTs include:

• ENGAGE AF-TIMI 48 (Effective aNticoaGulation with factor xA next GEneration in Atrial Fibrillation), in AF patients at moderate-to-high risk of thromboembolic events
• Hokusai VTE (Edoxaban in Venous Thromboembolism), in patients with either acute symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE) or both
• 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 nonvalvular 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

EDOSURE is our commitment to adding to the scientific body of knowledge around edoxaban in a variety of AF and VTE patients, including those who are vulnerable.

For more information, please visit: https://www.daiichisankyo.com/rd/pipeline/products/ecrp/index.html

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: 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

1. Koretsune, Y. et al. The Global ETNA-AF registry programme: Snapshot baseline demographics and patient characteristics from 24,431 atrial fibrillation patients on edoxaban. Presented at the European Society of Cardiology Congress, Munich, 2018.
2. De Caterina, R. et al. Baseline stroke and bleeding risks in the Global Edoxaban Treatment in Routine Clinical Practice in Patients with Nonvalvular Atrial Fibrillation programme (Global ETNA-AF): First snapshot analysis. Presented at the European Society of Cardiology Congress, Munich, 2018.
3. De Caterina, R. et al. Prior antithrombotic therapy: A snapshot of 24,431 patients from the Global Edoxaban Treatment in Routine Clinical Practice in Patients with Nonvalvular Atrial Fibrillation programme (Global ETNA-AF). Presented at the European Society of Cardiology Congress, Munich, 2018.
4. Edoxaban Treatment in Routine Clinical Practice for Patients With Non Valvular Atrial Fibrillation (ETNA-AF-EU). Available at: https://clinicaltrials.gov/ct2/show/NCT02944019. [Last accessed: August 2018].
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6. Edoxaban Treatment in Routine Clinical Practice for Patients With Non-valvular Atrial Fibrillation (ETNA-AF-Hong Kong). Available at: https://clinicaltrials.gov/ct2/show/NCT03247582. [Last accessed: August 2018].
7. Edoxaban Treatment in Routine Clinical Practice for Patients With Non-Valvular Atrial Fibrillation (NVAF). Available at: https://clinicaltrials.gov/ct2/show/NCT03247569. [Last accessed: August 2018].
8. ETNA-AF-Japan. Available at: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000019728. [Last accessed: August 2018].
9. Giugliano R, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369(22):2093-2104.
10. National Heart, Lung and Blood Institute ? What is Atrial Fibrillation. Available at: http://www.nhlbi.nih.gov/health/dci/Diseases/af/af_diagnosis.html. [Last accessed: August 2018].
11. Iqbal MB, et al. Recent developments in atrial fibrillation. BMJ. 2005;330(7485):238?43.
12. Kirchof P, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. European Society of Cardiology. 2016;37, 2893?2962.
13. Krijthe BP, et al. Projections on the number of individuals with atrial fibrillation in the European Union, from 2000 to 2060. Eur Heart J. 2013;34(35):2746-2751.
14. Ball J, et al. Atrial fibrillation: Profile and burden of an evolving epidemic in the 21st century. Int J Card. 2013;167:1807-1824.

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

August 2018, EDX/18/0394