• Publication highlights Europe-specific one-year follow-up findings for atrial fibrillation (AF) patients in routine clinical practice, which indicate that rates of stroke, systemic embolism, and major bleeding are low in edoxaban treated patients¹
• Findings are part of growing scientific evidence reinforcing the safety and effectiveness of edoxaban in routine care in Europe
• The global ETNA-AF programme, which includes ETNA-AF-Europe, is the largest prospective, non-interventional study investigating a single NOAC to date

Munich, Germany (20 August 2020) – Daiichi Sankyo Europe GmbH (hereafter, “Daiichi Sankyo”) today announced the publication of one-year follow up results from the ongoing ETNA-AF Europe (Edoxaban Treatment in routiNe clinical prActice for patients with non-valvular Atrial Fibrillation) registry in the European Heart Journal – Cardiovascular Pharmacotherapy.¹

Published data highlights Europe-specific, routine clinical practice findings, which indicate that rates of stroke, systemic embolism, and major bleeding are considered to be low in a large unselected cohort of AF patients being treated with edoxaban (known by the brand name LIXIANA^®).¹

ETNA-AF-Europe is a multinational, multicentre, post-authorisation, observational study of 13,092 patients across Europe, and is part of the largest prospective, non-interventional study programme investigating a single non-vitamin K antagonist oral anticoagulant (NOAC) in patients with non-valvular atrial fibrillation (NVAF) to date.¹ While NOAC use in clinical practice is increasingly becoming the standard of care with several registries and retrospective analyses having assessed outcomes of three of the four available NOACs, prior to ETNA-AF, edoxaban data had been more limited.¹

“Findings noted in ETNA-AF-Europe now complement the outcomes reported in other observational data sets on NOACs. The strengths of the study include a large sample size, a four-year duration, a prospective study design, an international setting including 10 countries, and the lack of explicit exclusion criteria,” said study author Professor Paulus Kirchhof, MD, Director of the Department of Cardiology, University Heart and Vascular Centre UKE Hamburg, Germany, and Professor of Cardiovascular Medicine, Institute of Cardiovascular Sciences at University of Birmingham, UK. “The low rates of stroke, major bleeding, and death illustrate that anticoagulation with edoxaban, similar to other NOACs, is an effective tool to reduce serious outcomes in patients with atrial fibrillation.”

Advancing age, accumulation of comorbidities and frailty are believed to increase thromboembolic and bleeding risks in patients with AF. The ETNA-AF-Europe dataset demonstrates a low and constant rate of intracranial haemorrhage (ICH) in both elderly and younger patients with AF.¹

The overall rates of major bleeding, stroke, and systemic embolism, as well as all-cause mortality, were considered low and linearly increasing during the one year follow-up:¹
• Major bleeding events were reported in 132 patients (1.05%/year), of which 51 (0.4%/year) were gastro-intestinal and 30 (0.2%/year) were ICH.
• Stroke or systemic embolism occurred in 103 patients (0.82%/year).
• In total, 442 patients died (3.5%/year), of whom 206 patients (1.63%/year) died of cardiovascular causes.

Findings observed in ETNA-AF-Europe were in line with those reported in the non-Asian ethnicity cohort of the ENGAGE AF-TIMI 48 study. Including ETNA-AF-Europe, the data accumulated so far reinforce edoxaban’s ability to improve outcomes in elderly and frail patients.¹

Notably, the permanent discontinuation rate at one year was relatively low (9.1%) compared with other registries (e.g. discontinuation rate of 20.1% at 1 year was noted in in a similar Post Authorisation Safety Study (PASS) registry with a different NOAC).^1,2 The wider global ETNA-AF programme has so far collected data from 24,962 patients in 2,242 sites in Japan, Korea, Taiwan and Europe. The study is part of the Edoxaban Clinical Research Programme, EDOSURE, which includes more than 10 randomised, controlled trials, registries and non-randomised clinical studies.

– ENDS –

About ETNA-AF

ETNA-AF (Edoxaban Treatment in routiNe clinical prActice in patients with nonvalvular Atrial Fibrillation) is a global programme 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 use of edoxaban in routine clinical practice, including the safety and efficacy profile in non-preselected patients with NVAF.^3,4,5,6,7

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.⁸

AF is the most common type of heart rhythm disorder and is associated with substantial morbidity and mortality.⁹ More than six million Europeans are diagnosed with AF, and this figure is expected to at least double over the next 50 years.^10,11 Compared to those without AF, people with the arrhythmia have a 3-5 times higher risk of stroke.¹² One in five of all strokes are as a result of AF.¹⁰

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 30 countries and regions around the world.

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 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 program, EDOSURE, which is comprised of more than 10 RCTs (randomised, controlled trials), registries and non-randomised clinical studies, including completed, ongoing and future research. Our goal is to generate new edoxaban clinical and real-world-data regarding its 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)
− STABLED Study (STroke secondary prevention with catheter ABLation and EDoxaban for patients with non-valvular atrial fibrillation) in Japan
– ENRICH-AF (EdoxabaN foR IntraCranial Hemorrhage survivors with Atrial Fibrillation, an investigator initiated phase III study)

In addition, global and regional registry and non-randomised clinical studies provide important real-world and clinical data about the use of edoxaban and other oral anticoagulants in everyday practice; these 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
− RYOUMA (Real world ablation therapY with anti-cOagUlants in Management of Atrial fibrillation) Registry in Japan
− KYU-RABLE (Multicenter study associated with KYU-shu to evaluate the efficacy and safety of edoxaban in patients with non-valvulaR Atrial fiBriLlation undergoing cathEter ablation) in Japan
− BPV-AF (Atrial Fibrillation with BioProsthetic valve) Registry in Japan

Through EDOSURE, 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.

Contact

Dr. Wolfgang Schiessl
Daiichi Sankyo Europe GmbH
Director Product PR and Communications
Cardiovascular Europe
+49 151 1714 7317

About Daiichi Sankyo

Daiichi Sankyo Group is dedicated to the creation and supply of innovative pharmaceutical therapies to improve standards of care and address diversified, unmet medical needs of people globally by leveraging our world-class science and technology. With more than 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 cardiovascular diseases, under the Group’s 2025 Vision to become a “Global Pharma Innovator with Competitive Advantage in Oncology,” Daiichi Sankyo is primarily focused on providing novel therapies in oncology, as well as other research areas centered around rare diseases and immune disorders. 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

1. de Groot, JR, et al. Edoxaban for stroke prevention in atrial fibrillation in routine clinical care: 1-year follow-up of the prospective observational ETNA-AF-Europe study. EHJ-Cardiovascular pharmacotherapy 2020. https://doi.org/10.1093/ehjcvp/pvaa079.
2. Camm AJ, et al. XANTUS Investigators. XANTUS: a real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation. Eur Heart J 2016;37:1145–1153.
3. Edoxaban Treatment in Routine Clinical Practice for Patients With Non Valvular Atrial Fibrillation (ETNA-AF-EU). Available at: https://clinicaltrials.gov/ct2/show/NCT02944019. Accessed August 2020.
4. Edoxaban Treatment in Routine Clinical Practice for Patients With Atrial Fibrillation in Korea and Taiwan (ETNA-AF-KOR-TWN). Available at: https://clinicaltrials.gov/ct2/show/NCT02951039. Accessed August 2020.
5. 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. Accessed August 2020.
6. Edoxaban Treatment in Routine Clinical Practice for Patients With Non-Valvular Atrial Fibrillation (NVAF). Available at: https://clinicaltrials.gov/ct2/show/NCT03247569. Accessed August 2020.
7. ETNA-AF-Japan. Available at: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000019728. Accessed August 2020.
8. National Heart, Lung and Blood Institute – What is Atrial Fibrillation. Available at: http://www.nhlbi.nih.gov/health/dci/Diseases/af/af_diagnosis.html. Accessed August 2020.
9. Iqbal MB, et al. Recent developments in atrial fibrillation. BMJ. 2005;330(7485):238–43.
10. Camm AJ, et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010;31(19):2369-2429.
11. 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.
12. Ball J, et al. Atrial fibrillation: Profile and burden of an evolving epidemic in the 21st century. Int J Card. 2013;167:1807-1824.

• Daiichi Sankyo presented five abstracts from the Global and European ETNA-VTE registry studies at ISTH 2020 Virtual Congress
• Data are from 4,595 VTE patients (mean age 64) from 583 sites across Europe, Japan and other East and South-east Asian countries
• Real-world study adds to the growing body of evidence supporting edoxaban-use in the ageing and elderly populations

Munich, Germany (14 July 2020) – Daiichi Sankyo Europe GmbH (hereafter, “Daiichi Sankyo”) today announced results from five analyses of 12-month data from ETNA-VTE (Edoxaban Treatment in routiNe clinical prActice in patients with Venous ThromboEmbolism), a non-interventional safety study evaluating edoxaban (known by the brand name LIXIANA^®), the non-vitamin K antagonist oral anticoagulant (NOAC). In routine clinical practice in 4,595 (mean age 64) venous thromboembolism (VTE) patients, overall findings showed low rates of bleeding and VTE recurrence in a range of VTE sub-populations and were presented during the International Society on Thrombosis and Haemostasis (ISTH) 2020 Virtual Congress.^1,2,3

VTE is a major cause of morbidity and mortality globally.⁴ Every year in Europe more than 1.5 million people experience a VTE event, with the risk of occurrence increasing exponentially with age (doubling every 10 years after the age of 50),^5,6 making the elderly most vulnerable. A prior incidence of a VTE is the most significant risk factor of a second occurrence.⁶ Reducing the risk of VTE recurrence and bleeding is the cornerstone of current interventions in this patient group.

“These real-world findings provide clinicians with additional evidence of edoxaban’s safety and efficacy in specific VTE patient populations that are considered high-risk or have comorbidities,” said Dr. Alexander T. Cohen, MBBS, MSc, MD, FRACP, FESC, Vascular Physician and Epidemiologist at Guy’s and St. Thomas’ Hospital, King’s College, London. “This is of particular significance for ageing patients and those who treat them, as the elderly are at greatest risk due to the high prevalence of predisposing comorbidities and acute illnesses, making edoxaban an appropriate treatment for this population.”

Global ETNA-VTE results
A global sub-analysis (abstract PB2409) showed that at 12 months, rates of major bleeding were low across all age groups, recurrent VTE decreased with increasing age, and all-cause mortality increased with age as would be expected. However, most of the mortalities were not cardiovascular (CV)-related.¹ Per year, globally:¹
• VTE recurrence occurred in 3.65% of patients aged 65 or below, 2.83% of those aged 65-75, 2.30% of those aged 75-85 and 3.07% of those aged 85 or over.
• ISTH-defined major bleeding occurred in 1.34% of patients aged 65 or below, 3.16% of patients aged 65-75, 2.97% of patients aged 75-85 and 5.72% of patients aged 85 or over.
• CV-related mortality occurred in 0.35% of patients aged 65 or below, 1.08% of patients aged 65-75, 1.96% of patients aged 75-85 and 3.04% of patients aged 85 or over.

ETNA-VTE Europe results
The first of two European sub-analyses (abstract PB2461) showed low rates of major bleeding and VTE recurrence in both patients with pulmonary embolism (PE), with or without deep vein thrombosis (DVT), and patients with DVT alone.³ Of note, patients with PE, with or without DVT, had a tendency towards a higher risk of mortality and bleeding events than those with DVT alone, but they also had higher risk baseline characteristics.³ Per year, in the European index VTE event group:³
• Major bleeding occurred in 2.39% of patients with PE, with or without DVT, and 1.57% of patients with DVT alone.
• VTE recurrence of any kind occurred in 2.89% of patients with PE, with or without DVT, and 2.78% of those with DVT alone.

The second European sub-analysis (abstract PB2432), which stratified patients by body mass index (BMI) (BMI 18.5-<25 kg/m₂ [normal weight], BMI 25-<30 kg/m₂ [overweight], BMI ≥30 kg/m₂ [obese]), showed that obesity did not substantially affect the risks of recurrent VTE and other bleeding complications.² Per year, in the European BMI group:²
• VTE recurrence occurred in 2.67% of patients overall (2.44%, 2.83% and 2.71% respectively).
• Major bleeding occurred in 1.69% of patients overall (1.75%, 2.00% and 1.11% respectively).
• All-cause mortality occurred in 2.16% of patients overall (2.97%, 1.77% and 2.39% respectively).

“These are important new real-world data, which add to edoxaban’s growing knowledge base supporting its use in a range of VTE patients,” said Wolfgang Zierhut MD, Head Antithrombotic and Cardiovascular Therapeutic Area at Daiichi Sankyo Europe. “At Daiichi Sankyo, we are committed to continuing the evaluation of safety and efficacy of edoxaban in a broad range of cardiovascular patients through ETNA-VTE and other studies included in the Edoxaban Clinical Research Programme, EDOSURE.”

Additional finding from two further Global and European ETNA-VTE abstracts (PB2478 and PB2434) showed that high versus low bleeding risk (as identified by the VTE-BLEED score) was associated with similar VTE recurrence risk but higher all-cause and cardiovascular mortality and incidences of any bleeding type or category, and that edoxaban is largely used adequately in real-world practice in Europe, respecting the recommendations for treatment initiation, dosing, and dose adjustments in special patient populations.^7,8

ETNA-VTE is part of the global ETNA programme, which is the largest and most comprehensive repository of routine clinical practice data on the use, effectiveness and safety of a single NOAC in patients with atrial fibrillation (AF) or VTE. This study is also one of more than 10 randomised, controlled trials (RCTs), registries and non-randomised clinical studies that comprise the Edoxaban Clinical Research Programme, EDOSURE.

– ENDS –

About ETNA-VTE

ETNA-VTE is a non-interventional study on Edoxaban Treatment in routiNe clinical prActice in patients with Venous ThromboEmbolism (including DVT and PE). It aimed to enrol a total of 4,500 VTE patients from sites across Europe, Japan, and East and Southeast Asia.⁹

The primary objective is the overall symptomatic VTE recurrence rate during an overall observational period of 18 months in unselected patients with acute VTE.⁹ The co-primary objective is to collect rates of real-world safety data on bleeding events, drug-related adverse events and mortality in VTE patients treated with edoxaban.⁹

About Venous Thromboembolism

VTE is an umbrella term for two conditions, DVT and PE.¹⁰ DVT is a disease caused by a blood clot found in deep veins, usually within the lower leg, thigh or pelvis, although they can occur in other parts of the body as well. PE occurs when part of a clot detaches and lodges in the pulmonary arteries, causing a potentially fatal condition.¹⁰ The annual incidence of VTE in developed countries is estimated to be 1-3 per 1,000 adults.^5,11 A prior incidence of a VTE is the most significant risk factor of a second occurrence.⁶

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 30 countries and regions around the world.

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 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 program, EDOSURE, which is comprised of more than 10 RCTs (randomised, controlled trials), registries and non-randomised clinical studies, including completed, ongoing and future research. Our goal is to generate new edoxaban clinical and real-world-data regarding its 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)
− STABLED Study (STroke secondary prevention with catheter ABLation and EDoxaban for patients with non-valvular atrial fibrillation) in Japan
– ENRICH-AF (EdoxabaN foR IntraCranial Hemorrhage survivors with Atrial Fibrillation, an investigator initiated phase III study)

In addition, global and regional registry and non-randomised clinical studies provide important real-world and clinical data about the use of edoxaban and other oral anticoagulants in everyday practice; these 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
− RYOUMA (Real world ablation therapY with anti-cOagUlants in Management of Atrial fibrillation) Registry in Japan
− KYU-RABLE (Multicenter study associated with KYU-shu to evaluate the efficacy and safety of edoxaban in patients with non-valvulaR Atrial fiBriLlation undergoing cathEter ablation) in Japan
− BPV-AF (Atrial Fibrillation with BioProsthetic valve) Registry in Japan

Through EDOSURE, 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.

Contact

Dr. Wolfgang Schiessl
Daiichi Sankyo Europe GmbH
Director Product PR and Communications
Cardiovascular Europe
+49 151 1714 7317

About Daiichi Sankyo

Daiichi Sankyo Group is dedicated to the creation and supply of innovative pharmaceutical therapies to improve standards of care and address diversified, unmet medical needs of people globally by leveraging our world-class science and technology. With more than 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 cardiovascular diseases, under the Group’s 2025 Vision to become a “Global Pharma Innovator with Competitive Advantage in Oncology,” Daiichi Sankyo is primarily focused on providing novel therapies in oncology, as well as other research areas centered around rare diseases and immune disorders. 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

1. Agnelli, G. et al. Edoxaban Treatment of Venous Thromboembolism in Routine Clinical Practice in the Non-Interventional Global ETNA-VTE Program: A Sub-analysis by Age Groups. Poster presented at the International Society on Thrombosis and Haemostasis (ISTH) 2020 Virtual Congress.
2. Schindewolf, M. et al. ETNA-VTE Europe: The Effect of Body Mass Index on 12-Month Outcomes in VTE Patients with Edoxaban. Poster presented at the International Society on Thrombosis and Haemostasis (ISTH) 2020 Virtual Congress.
3. Coppens, M. et al. Association between index venous thromboembolism (VTE) event and 12-months outcomes for patients in routine clinical practice enrolled in the Edoxaban Treatment in routine cliNical prActice for patients with acute VTE in Europe (ETNA-VTE-Europe) registry. Poster presented at the International Society on Thrombosis and Haemostasis (ISTH) 2020 Virtual Congress.
4. ISTH Steering Committee for World Thrombosis Day. Thrombosis: A major contributor to global disease burden. J Thromb Haemost. 2014 Oct;12(10):1580-90.
5. The Coalition to Prevent VTE. Available at: http://www.coalitiontopreventvte.org/INDEX_CFM/T/THE_BURDEN_OF_VTE/VID/DCD0A03F_1422_16B3_78E0B9EB0571.HTM. Last accessed June 2020.
6. Zagaria, M. Venous Thrombosis: Pathogenesis and Potential for Embolism. US Pharm. 2009;34:22-24.
7. Cohen, A. et al. ETNA-VTE Global: Evaluation of Bleeding Risk Based on VTE-BLEED Score on 12-month Outcomes in a Population Treated with Edoxaban. Poster presented at the International Society on Thrombosis and Haemostasis (ISTH) 2020 Virtual Congress.
8. Cohen, A. et al. ETNA VTE Europe: A Contemporary Snapshot of VTE Patients Treated with Edoxaban in Clinical Practice across Eight European Countries. Poster presented at the International Society on Thrombosis and Haemostasis (ISTH) 2020 Virtual Congress.
9. De Caterina, R. et al. The global Edoxaban Treatment in routine cliNical prActice (ETNA) noninterventional study program: rationale and design. Clin Cardiol. 2019;42(12):1147-1154.
10. National Heart, Lunch, and Blood Institute. Venous Thromboembolism. Available: https://www.nhlbi.nih.gov/health-topics/venous-thromboembolism. Last accessed June 2020.
11. Braekkan, S. K. et al. Body height and risk of venous thromboembolism: The Tromsø Study. Am J Epidemiol. 2010;171:1109–15.

• One-year outcomes of real-world edoxaban-treated European patients from the Global ETNA-AF registry showed low rates of potentially life-threatening bleeding and low CV events in elderly NVAF patients¹
• The Global ETNA-AF programme is currently the largest and most comprehensive repository of routine clinical practice data on the use, effectiveness, and safety of a single NOAC in AF patients
• Real-world Europe-specific findings demonstrate effectiveness and safety of edoxaban in routine clinical care across Europe¹

Munich, Germany (12 October 2019) – Daiichi Sankyo Europe GmbH (hereafter, “Daiichi Sankyo”) today announced one-year follow-up results from an analysis of 12,574 European non-valvular atrial fibrillation (NVAF) patients, mostly elderly, treated with edoxaban (known by the brand name LIXIANA^®). One-year results from the ongoing Global ETNA-AF (Edoxaban Treatment in routiNe clinical prActice) registry, providing a snapshot of characteristics and outcomes from a broad range of NVAF patients receiving edoxaban in routine clinical care, were presented today at the Great Wall International Congress of Cardiology (GW-ICC) 2019, in Beijing, China.

Overall, results from ETNA-AF at one year showed low rates of bleeding (major and gastrointestinal [GI]), intracranial haemorrhage (ICH) and ischaemic events during the first year of edoxaban therapy.¹ Per year, in the 12,574 patients from 825 sites² in Europe:¹
• ISTH-defined major bleeding occurred in only 125 (1.05%) patients, ICH occurred in 28 (0.23%) patients, and major GI bleeding occurred in 47 (0.39%) patients
• Ischaemic stroke occurred in 65 (0.54%) patients, transient ischaemic attack (TIA) occurred in 44 (0.37%) patients, and haemorrhagic stroke occurred in 13 (0.11%) patients.

Rates of systemic embolic events (SEE) and myocardial infarction (MI) were generally low. Per year in Europe:¹
• SEE occurred in 13 (0.11%) patients
• MI occurred in 63 (0.53%) patients.

Additionally, mortality rates were low. In total, per year in Europe:¹
• All-cause mortality occurred in 425 (3.55%) patients and cardiovascular mortality occurred in 200 (1.67%) patients.

While rates of stroke, bleeding and all-cause and cardiovascular mortality increased with age, an age-related increase in ICH was not apparent and rates were low in each age group.

“In routine clinical practice, the rates of major and clinically-relevant non-major (CRNM) bleeding in elderly edoxaban-treated patients were lower than those observed in clinical trial settings. Additionally, rates of all other cardiovascular events were also low in these patients,” said Professor Raffaele De Caterina, Professor of Cardiology, Institute of Cardiology at the University of Pisa, Italy. “Atrial fibrillation is the most common form of arrhythmia in patients over the age of 65, and its prevalence increases with age. As such, it is critical that we understand the safety and efficacy profile of edoxaban in elderly populations.”

The wider Global ETNA-AF programme, which at present is the largest and most comprehensive repository of routine clinical practice data on the use, effectiveness, and safety of a single NOAC in patients with atrial fibrillation (AF), collected data from 24,962 patients in 2,242 sites in Japan, Korea/Taiwan and Europe.

“These positive results provide great insight into the safety and efficacy profile of edoxaban in NVAF patients, particularly in those who are elderly and/or those with comorbidities, who are considered at higher risk of cardiovascular events,” said Wolfgang Zierhut, MD, Executive Director Medical Affairs and Head Thrombosis and Cardiovascular at Daiichi Sankyo Europe. “Findings from ETNA-AF demonstrate that Phase III efficacy and safety results from the ENGAGE AF-TIMI-48 clinical study are being confirmed in regular routine clinical care across the region.”

– ENDS –

About ETNA-AF

ETNA-AF (Edoxaban Treatment in routiNe clinical prActice in patients with nonvalvular Atrial Fibrillation) is a global programme 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 use of edoxaban in routine clinical practice, including the safety and efficacy profile in non-preselected patients with NVAF.^3,4,5,6,7

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.⁸

AF is the most common type of heart rhythm disorder and is associated with substantial morbidity and mortality.⁹ More than six million Europeans are diagnosed with AF, and this figure is expected to at least double over the next 50 years.^10,11 Compared to those without AF, people with the arrhythmia have a 3-5 times higher risk of stroke.¹² One in five of all strokes are as a result of AF.⁹

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 30 countries and regions around the world.

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 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) 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-randomised clinical studies, including completed, ongoing and future research. Our goal is to generate new edoxaban clinical and real-world-data regarding its 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)
− STABLED Study (STroke secondary prevention with catheter ABLation and EDoxaban for patients with non-valvular atrial fibrillation) in Japan
– ENRICH-AF (EdoxabaN foR IntraCranial Hemorrhage survivors with Atrial Fibrillation, an investigator initiated phase III study)

In addition, global and regional registry and non-randomised clinical studies provide important real-world and clinical data about the use of edoxaban and other oral anticoagulants in everyday practice; these 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
− RYOUMA (Real world ablation therapY with anti-cOagUlants in Management of Atrial fibrillation) Registry in Japan
− KYU-RABLE (Multicenter study associated with KYU-shu to evaluate the efficacy and safety of edoxaban in patients with non-valvulaR Atrial fiBriLlation undergoing cathEter ablation) in Japan
− BPV-AF (Atrial Fibrillation with BioProsthetic valve) Registry in Japan

Through EDOSURE, 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 therapies to improve standards of care and address diversified, unmet medical needs of people globally by leveraging our world-class science and technology. With more than 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 cardiovascular diseases, under the Group’s 2025 Vision to become a “Global Pharma Innovator with Competitive Advantage in Oncology,” Daiichi Sankyo is primarily focused on providing novel therapies in oncology, as well as other research areas centered around rare diseases and immune disorders. For more information, please visit: http://www.daiichisankyo.com.

Contact

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

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. De Caterina, R. et al. One-year Outcomes of Major Bleeding, Stroke and Mortality in Approximately 25,000 AF Patients Treated with Edoxaban in Routine Clinical Practice: Snapshot from Global Noninterventional ETNA-AF Program. Abstract presented at GW-ICC Congress 2019.
2. De Caterina, R. et al. Characteristics of patients initiated on edoxaban in Europe: baseline data from edoxaban treatment in routine clinical practice for patients with atrial fibrillation (AF) in Europe (ETNA-AF-Europe). BMC Cardiovasc Disord. 2019;19(1):165.
3. 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: October 2019].
4. Edoxaban Treatment in Routine Clinical Practice for Patients With Atrial Fibrillation in Korea and Taiwan (ETNA-AF-KOR-TWN). Available at: https://clinicaltrials.gov/ct2/show/NCT02951039. [Last accessed: October 2019].
5. 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: October 2019].
6. Edoxaban Treatment in Routine Clinical Practice for Patients With Non-Valvular Atrial Fibrillation (NVAF). Available at: https://clinicaltrials.gov/ct2/show/NCT03247569. [Last accessed: October 2019].
7. ETNA-AF-Japan. Available at: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000019728 [Last accessed: October 2019].
8. 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: October 2019].
9. Iqbal MB, et al. Recent developments in atrial fibrillation. BMJ. 2005;330(7485):238–43.
10. Camm A, et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010;31(19):2369-2429.
11. 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.
12. Ball J, et al. Atrial fibrillation: Profile and burden of an evolving epidemic in the 21st century. Int J Card. 2013;167:1807-1824.