Daiichi Sankyo's Once-Daily Lixiana® (edoxaban) Receives Positive CHMP Opinion for the Prevention of Stroke and Systemic Embolism in Non-Valvular Atrial Fibrillation and for the Treatment and Preventi

Tokyo (ots/PRNewswire) -

- The European Committee for Medicinal Products for Human Use recommended
approval of once-daily Lixiana(R)
- The positive opinion is based on data from the ENGAGE AF-TIMI 48 and
Hokusai-VTE studies, the largest single comparative global trials of a novel oral
anticoagulant in patients with non-valvular atrial fibrillation or venous
thromboembolism, involving 21,105 and 8,292 patients, respectively
- Daiichi Sankyo looks forward to receiving approval decision by the European
Commission soon, which is the basis for marketing authorisation in all European Union
member states

Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) today
announced that the European Committee for Medicinal Products for
Human Use (CHMP) has recommended approval of Lixiana(R) (edoxaban),
an oral, once-daily selective factor Xa inhibitor, for the prevention
of stroke and systemic embolism (SE) in adult patients with
non-valvular atrial fibrillation (NVAF) with one or more risk
factors. The CHMP also recommended approval of Lixiana for the
treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE),
and prevention of recurrent DVT and PE in adults. The two related
conditions DVT and PE are collectively referred to as venous
thromboembolism (VTE).[1]

"The CHMP recommendation to approve once-daily edoxaban for the
NVAF and VTE indications is an important milestone for our company,"
said Glenn Gormley, MD, PhD, Senior Executive Officer and Global Head
of R&D, Daiichi Sankyo Company, Limited and Executive Chairman and
President, Daiichi Sankyo, Inc. "The European regulatory committee
has recognised the positive benefit-risk profile of the 60 mg dosing
regimen [with a dose reduction to 30 mg in selected patients with
creatinine clearance (CrCL) 15-50 mL/min, body weight less than or
equal to 60 kg, or concomitant use of certain P-glycoprotein (P-gp)
inhibitors]."

The CHMP opinion to approve once-daily edoxaban for the prevention
of stroke and SE in adult patients with NVAF with one or more risk
factors and for the treatment and prevention of recurrent VTE (DVT
and PE) is based on the data of the phase 3 ENGAGE AF-TIMI 48 and
Hokusai-VTE studies, respectively.[2],[3]

In the ENGAGE AF-TIMI 48 study, once-daily edoxaban 60 mg
demonstrated non-inferiority to well-managed warfarin for the primary
efficacy endpoint of occurrence of stroke or SE in patients with NVAF
(1.18% vs. 1.50% per year, respectively; hazard ratio [HR], 0.79;
97.5% confidence interval [CI], 0.63 to 0.99, p<0.001). In addition,
once-daily edoxaban 60 mg demonstrated a significant 20% risk
reduction of major bleeding in patients with NVAF compared to
warfarin (2.75% vs. 3.43% per year, respectively; HR, 0.80; 95% CI,
0.71 to 0.91, p<0.001).[2]

In the Hokusai-VTE study, once-daily edoxaban 60 mg was
non-inferior to warfarin for the primary efficacy endpoint of
recurrence of symptomatic VTE (3.2% vs. 3.5% of patients,
respectively; HR, 0.89; 95% CI, 0.70 to 1.13, p<0.001). In addition,
edoxaban demonstrated a significant 19% risk reduction of clinically
relevant bleeding in patients with VTE compared to warfarin (8.5% vs.
10.3% of patients, respectively; HR, 0.81; 95% CI, 0.71 to 0.94,
p=0.004).[3]

Atrial fibrillation (AF) is the most common type of heart rhythm
disorder, and is associated with substantial morbidity and
mortality.[4] More than six million Europeans suffer from AF and this
figure is expected to at least double over the next 50 years.[5],[6]
One in five of all strokes is as a result of AF.[5]

VTE is a major cause of morbidity and mortality.[7] VTE is a major
health problem in Europe, with more than one million VTE events or
deaths per year (France, Germany, Italy, Spain, Sweden, UK),
including more than 370,000 VTE-related deaths.[7]

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, randomized,
double-blind, double-dummy, global phase 3 clinical trial comparing
once-daily edoxaban with well-managed warfarin in 21,105 patients
with NVAF at moderate-to-high risk of thromboembolic events at 1,393
centers 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 follow-up. Patients were dose reduced for CrCL 30 to 50 mL/min,
body weight of 60 kg or less or certain P-gp 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 the Hokusai-VTE Study

Hokusai-VTE was a global, event-driven, randomized, double-blind,
double-dummy, parallel-group phase 3 clinical study involving 8,292
patients in 439 clinical sites across 37 countries to evaluate
once-daily edoxaban in patients with either acute symptomatic DVT, PE
or both. The Hokusai-VTE study was designed to reflect clinical
practice using a flexible treatment duration of 3-12 months in a
broad spectrum of VTE patients, including initial use of parenteral
anticoagulant (heparin) for 5-10 days, the proven global standard of
care. Patients were randomized to receive edoxaban 60 mg once-daily
(dose reduced to 30 mg for CrCL 30 to 50 mL/min, body weight of 60 kg
or less, or certain P-gp inhibitor use) or the comparator, warfarin,
following initial open-label enoxaparin or unfractionated heparin
therapy. In the comparator arm, patients received initial heparin
therapy concurrently with warfarin, titrated to a target INR of 2.0
to 3.0, followed by warfarin alone. The treatment duration was from 3
months and up to a maximum of one year. The duration of study
treatment was determined by the investigator based on the patient's
clinical features.[3] The full results were presented at the ESC
Congress 2013 in Amsterdam and published in the New England Journal
of Medicine.

About Edoxaban

Edoxaban is an investigational, oral, once-daily anticoagulant
that specifically inhibits factor Xa, which is an important factor in
the coagulation system that leads to blood clotting.[8] The global
edoxaban clinical trial program includes two phase 3 clinical
studies, Hokusai-VTE and ENGAGE AF-TIMI 48, which included nearly
30,000 patients combined. The results from these trials form the
basis of regulatory filings for edoxaban for symptomatic VTE in
patients with DVT and/or PE, and for the prevention of stroke and SE
in NVAF, respectively.[2],[3]

Edoxaban is currently marketed in Japan and the U.S. and has
received approval in Switzerland.[9],[10],[11] In other countries,
regulatory review is ongoing.

About Daiichi Sankyo

Daiichi Sankyo Group is dedicated to the creation and supply of
innovative pharmaceutical products to address the diversified, unmet
medical needs of patients in both mature and emerging markets. While
maintaining its portfolio of marketed pharmaceuticals for
hypertension, dyslipidemia and bacterial infections used by patients
around the world, the Group has also launched treatments for
thrombotic disorders and is building new product franchises.
Furthermore, Daiichi Sankyo research and development is focused on
bringing forth novel therapies in oncology and
cardiovascular-metabolic diseases, including biologics. The Daiichi
Sankyo Group has created a "Hybrid Business Model," to respond to
market and customer diversity and optimize growth opportunities
across the value chain. 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) Centers for Disease Control and Prevention. Deep Vein Thrombosis &
Pulmonary Embolism. Available at:
http://wwwnc.cdc.gov/travel/yellowbook/2014/chapter-2-the-pre-travel-consultation/deep-vein-thrombosis-and-pulmonary-embolism
. [Last accessed: April 2015].
2) Giugliano R, et al. Edoxaban versus warfarin in patients with atrial
fibrillation. N Engl J Med. 2013;369(22):2093-2104.
3) Bueller H, et al. Edoxaban versus warfarin for the treatment of symptomatic
venous thromboembolism. N Engl J Med. 2013;369(15):1406-1415.
4) Iqbal MB, et al. Recent developments in atrial fibrillation. BMJ.
2005;330(7485):238-43.
5) 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):2369-429
6) 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.
7) Cohen A, et al. Venous thromboembolism (VTE) in Europe. Thromb Haemost.
2007;98(4):756-764.
8) Ogata K, et al. Clinical safety, tolerability, pharmacokinetics, and
pharmacodynamics of the novel factor Xa inhibitor edoxaban in healthy volunteers. J
Clin Pharmacol. 2010;50(7):743-753.
9) Daiichi Sankyo press release - Daiichi Sankyo Launches New Formulation of
LIXIANA(R) 60 mg Tablets (edoxaban) in Japan. 8 Dec 2014. Available at:
http://www.daiichisankyo.com/media_investors/media_relations/press_releases/detail/006226.html
. [Last accessed: April 2015].
10) Daiichi Sankyo press release - SAVAYSA(TM) (edoxaban) Now Available in U.S.
Pharmacies. 9 February 2015. Available at:
http://www.daiichisankyo.com/media_investors/media_relations/press_releases/detail/006247.html
. [Last accessed: April 2015].
11) Daiichi Sankyo press release - Daiichi Sankyo's Once-Daily LIXIANA(R)
(edoxaban) Approved for the Prevention of Stroke and Systemic Embolism in Non-Valvular
Atrial Fibrillation and for the Treatment and Prevention of Recurrent Venous
Thromboembolism in Switzerland. 15 April 2015. Available at:
http://www.daiichisankyo.com/media_investors/media_relations/press_releases/detail/006269.html
. [Last accessed: April 2015].

Contact

Daria Munsel (Europe)
Daiichi Sankyo Europe GmbH
Edoxaban Comm. & Product PR Europe
+49(89)7808728

Yasuki Minobe (Global)
Daiichi Sankyo Group
Corporate Communication Department
+81(3)62251126

ots Originaltext: DAIICHI SANKYO EUROPE GmbH
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