MUNICH, December 12, 2017 /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.
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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_-_Product_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
- 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.
- 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.
- 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.
- Khalil J, et al. Venous thromboembolism in cancer patients: an
underestimated major health problem. World J Surg
Oncol. 2015;13:204.
- 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.
- 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.
- 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.
- Hisada Y, et al. Venous Thrombosis and Cancer: from Mouse
Models to Clinical Trials. J Thromb and
Haemost. 2015;13(8):1372-82.
- ClinicalTrials.gov. Cancer Venous Thromboembolism (VTE).
Available at: https://clinicaltrials.gov/ct2/show/NCT02073682.
[Last accessed: December 2017].
- 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].
- Van Beek E, et al. Deep vein thrombosis and pulmonary embolism.
New York: John Wiley & Sons,
2009. Print.
- Cohen A, et al. Venous thromboembolism (VTE) in Europe. Thromb Haemost.
2007;98(4):756-64.
- 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: December
2017].
- Braekkan, S. K. et al. Body height and risk of venous
thromboembolism: The Tromsø Study. Am J Epidemiol.
2010;171:1109-15.
- Zagaria, M. Venous Thrombosis: Pathogenesis and Potential for
Embolism. US Pharm. 2009;34:22-24.
- Ay C, et al. Prediction of venous thromboembolism in cancer
patients. Blood. 2010;116:5377-82.
- 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.
- Lee AYY, Levine N. Venous thromboembolism and cancer: Risks and
outcomes. Circ. 2003;107:I17-I21.
EDX/17/0329
Date of preparation: December
2017
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