European Results From Global ETNA-AF Registry Show Low Bleeding and Low Cardiovascular Event Rates in Elderly NVAF Patients on LIXIANA®▼ (edoxaban)

- 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, Oct. 12, 2019 /PRNewswire/ -- 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."

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 the 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, 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 foRIntraCranial 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 the edoxaban clinical research programme, 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: 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.