Once-Daily, Oral LIXIANA® (edoxaban) Met Primary Endpoint in Investigational Hokusai-VTE CANCER Study

Munich (ots/PRNewswire) -

For EU media only - not for US journalists

- Hokusai-VTE CANCER study is a phase 3b, prospective,
randomised, open-label, blind end-point (PROBE) study evaluating
edoxaban versus low molecular weight heparin (LMWH) dalteparin in
venous thromboembolism (VTE) associated with primarily active
cancer[1],[2],[3]
- Study met primary endpoint of non-inferiority in the recurrence
of VTE or ISTH-defined major bleeding[1],[2],[3]

Daiichi Sankyo Europe GmbH (hereafter, Daiichi Sankyo), today
announced results from the Hokusai-VTE CANCER study evaluating oral
edoxaban (known by the brand names LIXIANA® outside the U.S. and
SAVAYSA® in the U.S.), and found that edoxaban is non-inferior to
subcutaneous injectable LMWH dalteparin for the treatment of
cancer-associated VTE or major bleeding.[2],[3] The results of the
study were simultaneously published in the New England Journal of
Medicine (NEJM) and presented during the late-breaker session at the
59th American Society of Hematology (ASH) Annual Meeting in Atlanta,
Georgia.

To view the Multimedia News Release, please click:

https://www.multivu.com/players/uk/8236751-daily-oral-lixiana-canc
er-study-daiichi/

Hokusai-VTE CANCER is the first study with a direct oral
anticoagulant (DOAC), edoxaban, to meet pre-specified non-inferiority
criteria versus the standard of care dalteparin in this patient
population.[2],[3] The study met the primary objective of
non-inferiority of edoxaban for the composite outcome of first
recurrent VTE or ISTH-defined major bleeding during a 12-month study
period, which occurred in 67 of 522 patients (12.8%) in the edoxaban
group compared with 71 of 524 patients (13.5%) in the dalteparin
group (hazard ratio with edoxaban, 0.97; 95% CI, 0.70 to 1.36; P =
0.006 for non-inferiority) for a risk difference (edoxaban minus
dalteparin) of -0.7% (95% CI, -4.8 to 3.4).[2],[3] The difference in
risk for recurrent VTE was -3.4% (95% CI, -7.0 to 0.2) whereas the
corresponding difference in risk for major bleeding was 2.9% (95% CI,
0.1 to 5.6).[3] The frequencies of severe major bleeding events at
presentation (categories 3 and 4) were similar during treatment with
edoxaban or dalteparin (12 patients in each group,
respectively).[2],[3] There was no fatal bleed in the edoxaban group
versus two fatal bleedings in the dalteparin arm.[3]

The study also met the secondary outcome of event-free survival
(free of recurrent VTE, major bleeds or death) at 12 months, and
rates were similar between edoxaban and dalteparin (55.0% and 56.5%,
respectively).[2],[3] The trial was a PROBE design study and included
a broad spectrum of patients (n=1,050) with primarily active cancer
(98%): 53% of which had metastatic cancer and 72% of which were
receiving cancer therapy at randomisation.[2],[3] This is the largest
prospectively randomised clinical trial to have studied the benefit
risk of DOACs in cancer patients versus the current injectable
standard of care, dalteparin. Hokusai-VTE CANCER is the first study
to demonstrate that a DOAC, edoxaban, is non-inferior to the standard
of care, injectable LMWH (dalteparin), in this population.[2],[3]

"Cancer patients have a significantly increased risk of VTE, and
are a high-risk population since 82% of patients have one or more
pre-specified bleeding risk factors," said co-principal study
investigator Professor Harry Büller, from the Department of Vascular
Medicine at Academic Medical Center, Amsterdam, The Netherlands. "We
saw a lower rate of recurrent VTE with edoxaban compared to
dalteparin over the one-year study period. In addition, in the
edoxaban arm, we saw no bleeding fatalities and similar severity of
clinical presentation of major bleeding events compared to
dalteparin. The risk for VTE persists beyond six months for cancer
patients, therefore, the study duration of 12 months enabled the
evaluation of edoxaban over a longer time period."

VTE includes both deep vein thrombosis (DVT) and pulmonary
embolism (PE) and is the second leading cause of death in cancer
patients receiving chemotherapy.[4] Current guidelines recommend LMWH
for at least six months as the standard of care in cancer
patients,[5],[6],[7] and currently there is poor adherence to VTE
cancer treatment guidelines due to the requirement for daily
injections. The treatment of cancer-associated VTE is challenging
because these patients are at increased risk of both recurrent VTE
and major bleeding.[2] The occurrence of VTE increases the risk of
death 2-6-fold in cancer patients[4] and can interrupt cancer
treatment.[8]

"The use of an oral anticoagulant that alleviates the burdens
associated with a daily injectable drug, without loss of clinical
benefit, would represent an advance for cancer patients with VTE,"
said Hans J. Lanz, MD, Vice President, Global Medical Affairs,
Daiichi Sankyo. "The data will continue to add to the growing body of
knowledge in the Edoxaban Clinical Research Programme, which provides
key insights into the potential effects of edoxaban in VTE and AF
patients."

About the Hokusai-VTE CANCER study

Hokusai-VTE CANCER is a multinational, prospective, randomised,
open-label, blinded endpoint evaluation (PROBE) study, evaluating the
efficacy and safety of once-daily edoxaban compared to dalteparin for
the treatment of VTE associated with cancer.[1],[2],[3] The purpose
of the study was to evaluate edoxaban in comparison with dalteparin
in preventing the combined outcome of VTE recurrence or major
bleeding in patients with VTE associated with cancer.[1],[2],[3]
Other objectives include assessing the effects of treatment on VTE
recurrence, clinically relevant bleeding and event-free survival,
defined as the proportion of subjects over time free of recurrent
VTE, major bleeding events and death.[1],[2],[3] The study enrolled
1,050 patients across 13 countries in North America, Europe,
Australia and New Zealand.[2],[3] Patients were randomised to receive
edoxaban 60 mg once-daily (reduced to 30 mg edoxaban for patients
with creatinine clearance [CrCL] 30-50 mL/min, body weight <= 60 kg,
or concomitant use of P-glycoprotein [P-gp] inhibitors), following
treatment with LMWH for at least five days; or dalteparin SC 200
IU/kg once-daily for 30 days, then 150 IU/kg once-daily for the
remainder of the 12-month study.[1],[2],[3]

For more information please visit:
https://www.clinicaltrials.gov/ct2/show/NCT02073682.[9]

About Venous Thromboembolism

Venous thromboembolism (VTE) is an umbrella term for two
conditions, deep vein thrombosis (DVT) and pulmonary embolism (PE).
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.[10] PE occurs when part of a clot
detaches and lodges in the pulmonary arteries, causing a potentially
fatal condition.[11]

VTE is a major cause of morbidity and mortality.[12] In 25 EU
countries VTE exceeds 1.5 million events per year and the annual
incidence of VTE in developed countries is estimated to be 1-3 per
1,000 adults.[13],[14] A prior incidence of a VTE is the most
significant risk factor of a second occurrence, and after the age of
50, the risk doubles every ten years.[15]

About VTE and Cancer

VTE is a major cause of morbidity and mortality in patients with
cancer, with an annual incidence that can be as high as 20 percent
depending on the cancer type, background risk and time since
diagnosis.[16],[17] Patients with cancer have multiple risk factors
for VTE and the risk of VTE events increases in patients with cancer
receiving chemotherapy.[18] In addition, patients with cancer and VTE
have a lower survival rate than those without VTE.[18]

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 Switzerland, the U.K.,
Germany, Ireland, the Netherlands, Italy, Spain, Belgium, Austria,
Portugal, Canada, and other European countries.

The edoxaban Summary of Product Characteristics can be viewed
here: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Pro
duct_Information/human/002629/WC500189045.pdf.

About Edoxaban Clinical Research Programme (ECRP)

Daiichi Sankyo is committed to expanding scientific knowledge
about edoxaban, as demonstrated through our research programmes
evaluating its use in a broad range of cardiovascular conditions,
patient types and clinical settings in AF and VTE. The edoxaban
clinical research programme includes multiple RCTs (randomised,
controlled trials), registries and non-interventional studies, with
the goal of generating new clinical and real-world-data regarding its
use in AF and VTE populations. Daiichi Sankyo expects that more than
100,000 patients will participate in the edoxaban clinical research
programme, including completed, ongoing, and future research.

The RCTs include:

- 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 non valvular 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

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 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: 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. Van Es N, et al. Edoxaban for the treatment of venous
thromboembolism in patients with cancer - rationale and design of
the Hokusai-VTE-cancer study. Thromb Haemost.
2015;114(6):1268-76.
2. Raskob GE, Van Es N, Verhamme P, Carrier M, Di Nisio M, Garcia
DA, et al. LBA-6 A Randomized, Open-Label, Blinded Outcome
Assessment Trial Evaluating the Efficacy and Safety of
LMWH/Edoxaban Versus Dalteparin for Venous Thromboembolism
Associated with Cancer: Hokusai-VTE-Cancer Study. Abstract
presented at the Annual Society of Hematology Annual Meeting,
2017.
3. Raskob GE, van Es N, Verhamme, P, Carrier M, Di Nisio M, Garcia
DA, et al. Edoxaban for the treatment of cancer-associated
thromboembolism. N Engl J Med. 2017. DOI: 10.1056/NEJMoa1711948.
4. Khalil J, et al. Venous thromboembolism in cancer patients: an
underestimated major health problem. World J Surg Oncol.
2015;13:204.
5. Mandalà M, Falanga A, Roila F. Management of venous
thromboembolism (VTE) in cancer patients: ESMO Clinical Practice
Guidelines. Ann Oncol. 2011;22 (Suppl 6): vi85-vi92.
6. Kearon C, Aki EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H,
Huisman M, et al. Antithrombotic therapy fir VTE disease. CHEST
guidelines and expert panel report. Chest. 2016;149(2):315-52.
7. Lyman GH, Bohlke K, Khorana AA, Kuderer NM, Lee AY, Arcelus JI,
et al. Venous Thromboembolism Prophylaxis and Treatment in
Patients With Cancer: American Society of Clinical Oncology
Clinical Practice Guideline Update 2014. J Clin Oncol.
2015;11(3):e442-e444.
8. Hisada Y, et al. Venous Thrombosis and Cancer: from Mouse Models
to Clinical Trials. J Thromb and Haemost. 2015;13(8):1372-82.
9. ClinicalTrials.gov. Cancer Venous Thromboembolism (VTE).
Available at: https://clinicaltrials.gov/ct2/show/NCT02073682.
[Last accessed: December 2017].
10. Deep Vein Thrombosis (DVT) / Pulmonary Embolism (PE) - Blood Clot
Forming in a Vein. Centers for Disease Control and Prevention.
Available at: http://www.cdc.gov/ncbddd/dvt/facts.html. [Last
accessed: December 2017].
11. Van Beek E, et al. Deep vein thrombosis and pulmonary embolism.
New York: John Wiley & Sons, 2009. Print.
12. Cohen A, et al. Venous thromboembolism (VTE) in Europe. Thromb
Haemost. 2007;98(4):756-64.
13. The Coalition to Prevent VTE. Available at: http://www.coalitiont
opreventvte.org/INDEX_CFM/T/THE_BURDEN_OF_VTE/VID/DCD0A03F_1422_1
6B3_78E0B9EB0571.HTM. [Last accessed: December 2017].
14. Braekkan, S. K. et al. Body height and risk of venous
thromboembolism: The Tromsø Study. Am J Epidemiol.
2010;171:1109-15.
15. Zagaria, M. Venous Thrombosis: Pathogenesis and Potential for
Embolism. US Pharm. 2009;34:22-24.
16. Ay C, et al. Prediction of venous thromboembolism in cancer
patients. Blood. 2010;116:5377-82.
17. Khorana AA, et al. Thromboembolism is a leading cause of death in
cancer patients receiving outpatient chemotherapy. J Thromb
Haemost. 2007;5(3):632-634.
18. Lee AYY, Levine N. Venous thromboembolism and cancer: Risks and
outcomes. Circ. 2003;107:I17-I21.

EDX/17/0329

Date of preparation: December 2017

(Logo:
http://mma.prnewswire.com/media/618561/Daiichi_Sankyo_Logo.jpg )

Video:

https://www.multivu.com/players/uk/8236751-daily-oral-l
ixiana-cancer-study-daiichi/ (https://www.multivu.com/players/uk/8236751-daily-oral-lixiana-cancer-study-daiichi/)

ots Originaltext: Daiichi Sankyo Europe GmbH
Im Internet recherchierbar: http://www.presseportal.de

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

Original-Content von: Daiichi Sankyo Europe GmbH, übermittelt durch news aktuell