ETNA-AF Registry Data Provide Real-world Evidence of the Efficacy and Safety Profile of LIXIANA® (edoxaban) in Elderly NVAF Patients

- Global and European real-world outcome analyses in non-selected
atrial fibrillation (AF) patients on edoxaban, including those who
are elderly with comorbidities, were reported at ESC Congress 2019

- At present, the Global ETNA-AF programme is the largest and most
comprehensive repository of routine clinical practice data on the
use, effectiveness, and safety profile of a single non-vitamin K
antagonist oral anticoagulant (NOAC) in patients with non-valvular
atrial fibrillation (NVAF)

- One-year follow-up data from the ETNA-AF global registry showed
low rates of major bleeding (including haemorrhagic stroke and
intracranial haemorrhage [ICH]) in edoxaban-treated elderly and very
elderly AF patients with comorbidities in routine clinical care[1]

- European specific findings from ETNA-AF demonstrate that Phase
III efficacy and safety results from ENGAGE AF-TIMI-48 are being
confirmed in regular routine clinical care across the region[2]

Munich (ots/PRNewswire) - Daiichi Sankyo Europe GmbH (hereafter,
"Daiichi Sankyo") today announced one-year outcomes results from a
study of 24,962 patients with NVAF treated with edoxaban (known by
the brand name LIXIANA®), including elderly NVAF patients and those
with and without a history of intracranial haemorrhage (ICH).
One-year follow up data from the ETNA-AF (Edoxaban Treatment in
routiNe clinical prActice) study were presented today at ESC Congress
2019 in Paris, France, reporting the effectiveness and safety of
edoxaban in patients with NVAF.

Global ETNA-AF analyses

A new analysis, which reported the outcomes of 24,962
edoxaban-treated patients with NVAF at one year follow up supports
the treatment's safety and efficacy profile in elderly and very
elderly AF patients. The majority of these patients were aged 65
years or over.[1] Results showed that:[1]

- Rates of major bleeding (MB), as defined by the International
Society on Thrombosis and Haemostasis (ISTH), including ICH and
ischaemic stroke were generally low amongst all patient groups. Per
year, ISTH-defined MB occurred in 0.6% of patients aged <65, 0.9%
patients aged >=65-<75, 1.2% patients aged >=75-< 85 and 1.8%
patients aged >=85. ICH occurred in 0.2% patients aged <65, 0.3%
patients aged >=65-<75, 0.3% patients aged >=75-< 85 and 0.3%
patients aged >=85. Ishaemic stroke occurred in 0.6% of patients
aged <65, 0.7% patients aged >=65-<75, 0.9% patients aged >=75-< 85
and 1.3% patients aged >=85.
- Whilst all-cause and CV mortality was shown to increase with age,
as would be expected, CV mortality was a minor proportion of
all-cause mortality in all age groups. There was also no increase
in the rate of ICH with age. Per year, all-cause mortality/CV
mortality occurred in 35 (1.1%)/18 (0.5%) of patients aged <65, 136
(1.8%)/62 (0.8%) of those aged >=65-<75, 275 (3.3%)/116 (1.4%) of
those aged >=75-<85 and 196 (8.7%)/76 (3.4%) of those aged >=85.

"These findings are important because the prevalence of NVAF and
stroke risk, and therefore the need for oral anticoagulation, all
increase with age," said Professor Raffaele De Caterina, Professor of
Cardiology, Institute of Cardiology at the University of Pisa, Italy.
"Additionally, elderly patients are more likely to have other
comorbidities and to be on various medications that may interfere
with treatment. The data from this set of unselected patients support
edoxaban's growing evidence of safety profile and its use as an
effective treatment for elderly, and very elderly, AF patients in
regular clinical care. Of particular interest is the set of data
showing no apparent increase in the rate of intracranial haemorrhage
in edoxaban-treated patients as a function of age, while a high rate
of this occurrence and its increasing prevalence as a function of age
was shown in warfarin-treated patients."

Additionally, a further 1-year follow-up analysis of the
difference in outcomes between edoxaban-treated AF patients with
history of ICH (i.e. those at higher risk of stroke, death and
recurrent haemorrhage) and those without a history of ICH, showed
that:[3]

- Incidences of ISTH-defined MB (including ICH) and clinically
relevant non-major bleeding (CRNMB) were generally low in both
groups.
- ICH occurred in 3 (1.2%) patients with history of ICH and 56 (0.3%)
patients without history of ICH, per year. The rate of ischaemic
stroke was higher in patients with history of ICH (6 [2.4%]) than
in those without (165 [0.8%]), per year.

These new data suggest that edoxaban is an effective treatment
option for patients with or without prior ICH, whilst also
demonstrating the need for effective stroke prevention in NVAF
patients with a history of ICH.[3]

Wolfgang Zierhut, MD, Executive Director Medical Affairs and Head
Thrombosis and Cardiovascular at Daiichi Sankyo Europe commented:
"The wealth of new data we have shared at ESC Congress 2019 comes
from the largest and most comprehensive repository of real-world data
on edoxaban use. These new findings will feed into the ongoing
Edoxaban Clinical Research Programme, helping to expand the strong
evidence-base for the efficacy and safety of this important therapy
in patients with AF."

Further new European analyses at ESC 2019

Echoing the Global registry outcomes data, additional one-year
follow up analyses of 12,574 unselected elderly AF patients with
comorbidities, from ten European countries, showed that the incidence
of clinical events for both bleeding and stroke rates were low. Per
year, MB occurred in 1.05% (n=125), ICH occurred in 0.23% (n=28) and
any stroke or systemic embolic events occurred in 0.82% (n=98) of
cases.[2] All-cause mortality occurred in 3.55% of patients per year,
which can be rated as low in a high-risk context.[2]

This snapshot real-world analysis compared the baseline and first
year outcomes data from 12,574 patients (mean age of 73.6 years) with
the outcome data of the European cohort from the clinical Phase III
ENGAGE AF-TIMI 48 study,[2] which investigated the safety and
efficacy of edoxaban compared to warfarin, for the prevention of
stroke or stroke and systemic embolic events in patients with AF.[4]
In ETNA-AF, edoxaban was used in a broad range of elderly NVAF
patients. Additionally, dose reduction at baseline between the
ETNA-AF and ENGAGE AF-TIMI 48 was similar and overall there was a
good adherence (84%) to the European label.[5]

"It is interesting to note that the higher HAS-BLED score in
ETNA-AF compared to ENGAGE AF-TIMI 48 suggests that in real-world
clinical settings physicians are more comfortable using edoxaban in
patients with higher bleeding risk," said Raffaele De Caterina,
Professor of Cardiology, Institute of Cardiology at the University of
Pisa, Italy. "This new analysis reinforces the safety profile and
effectiveness of edoxaban in elderly NVAF patients at high CV risk,
but also suggest that the ENGAGE AF-TIMI 48 study efficacy results
are being largely confirmed in general practice."

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.[6],[7],[8],[9],[10]

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.[11]

AF is the most common type of heart rhythm disorder and is
associated with substantial morbidity and mortality.[12] More than
six million Europeans are diagnosed with AF, and this figure is
expected to at least double over the next 50 years.[13],[14]
Compared to those without AF, people with the arrhythmia have a 3-5
times higher risk of stroke.[15] 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 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 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 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.

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.

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

References:

[1] Wang, CC. et al. One-year outcomes of elderly patients with
atrial fibrillation: snapshot data from the Global Noninterventional
Program on Edoxaban Treatment in Routine Clinical Practice in Atrial
Fibrillation. Poster presented at ESC Congress 2019.

[2] De Caterina, R. et al. ETNA-AF Europe: First 1-year follow-up
snapshot analysis of more than 7,500 AF patients treated with
edoxaban in routine clinical practice. Poster presented at ESC
Congress 2019.

[3] Kirchhof, P. et al. Clinical characteristics and 1-year
outcomes in atrial fibrillation patients with or without history of
intracranial haemorrhage treated with edoxaban: data from the Global
ETNA-AF program. Poster presented at ESC Congress 2019.

[4] Giugliano, RP. et al. Edoxaban versus Warfarin in Patients
with Atrial Fibrillation. N Engl J Med. 2013; 369:2093-2104.

[5] 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;19:165.

[6] 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 2019].

[7] 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: August 2019].

[8] 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 2019].

[9] 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 2019].

[10] ETNA-AF-Japan. Available at: https://upload.umin.ac.jp/cgi-op
en-bin/ctr/ctr_view.cgi?recptno=R000019728 [Last accessed: August
2019].

[11] 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 2019].

[12] Iqbal, MB. et al. Recent developments in atrial fibrillation.
BMJ. 2005;330(7485):238-43.

[13] 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.

[14] 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.

[15] Ball, J. et al. Atrial fibrillation: Profile and burden of an
evolving epidemic in the 21st century. Int J Card.
2013;167:1807-1824.

Date of preparation: August 2019, EDX/19/0505

ots Originaltext: Daiichi Sankyo Europe GmbH
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