New Analysis Identifies Patient Populations With Cancer-associated VTE Who Could Benefit From Treatment With Oral, Once-daily LIXIANA® (edoxaban)

Munich (ots/PRNewswire) -

- Hokusai-VTE CANCER study showed that oral edoxaban is non-inferior
to subcutaneous injectable dalteparin, for the composite outcome of
recurrent venous thromboembolism (VTE) and major bleeding in
cancer-associated VTE
- This analysis provides benefit/risk assessment in different types
of cancer patient populations[1]
- In those with non-gastrointestinal cancer, the risk of major
bleeding was comparable[1]

Daiichi Sankyo Europe GmbH (hereafter, Daiichi Sankyo), today
announced the publication of a new analysis, focusing on the clinical
presentation, course and outcome of bleeding events, and the
associated tumour types from the Hokusai-VTE CANCER study.[1] The
data, published in the journal Thrombosis and Haemostasis, identified
that edoxaban is an appropriate alternative to dalteparin and that
further consideration is needed for the treatment of patients with
gastrointestinal cancer.[1]

The study found that the rate of recurrent VTE was 3.4% lower with
edoxaban compared to dalteparin (HR: 0.71; p = 0.09), whilst the rate
of major bleeding (as defined by the International Society on
Thrombosis and Haemostasis [ISTH]), was 2.9% higher (HR: 1.77; p =
0.04).[1] Major bleeding occurred in 32 out of 522 patients on
edoxaban, with 20 of the 32 (62.5%) requiring hospitalisation, whilst
in the dalteparin group, 16 out of 524 patients experienced major
bleeding, with 13 of the 16 (81.3%) requiring hospitalisation. The
number of patients needing admission to the intensive care unit was
18 (56.3%) in the edoxaban group versus 12 (75.0%) in the dalteparin
group.[1] It was identified that no patients had more than one major
bleed and that the additional instances of major bleeding with
edoxaban were confined to patients with gastrointestinal cancer and
predominantly occurred in the upper gastrointestinal tract.[1] Major
bleeding was classified according to the ISTH definition, though most
events only required red blood cell transfusion.[1] Among patients
with non-gastrointestinal cancer, the risk of major bleeding was
comparable.[1]

In patients with gastrointestinal cancer, the risk of bleeding in
the edoxaban group was 12.7%, compared to 3.6% among those treated
with dalteparin (HR: 4.0; 95% CI, 1.5-10.6; p = 0.005).[1] The risk
of severe major bleeding (ISTH category 3 or 4) in patients with
gastrointestinal cancer was comparable between patients on edoxaban
and dalteparin.[1] There were no fatal bleeds among those treated
with edoxaban versus two in the dalteparin group.[1]

"We've seen previously that edoxaban offers an alternative to
treatment with dalteparin for patients with cancer-associated VTE and
these findings provide valuable clarity on its optimum use in
patients with different types of cancer," said Professor Peter
Verhamme, Department of Vascular Medicine and Hemostasis, University
Hospitals Leuven, Leuven, Belgium. "It has been shown that for those
with non-gastrointestinal cancer, the risk of major bleeding is
comparable across patients treated with edoxaban versus dalteparin.
While we are still investigating what specifically causes the higher
risk of bleeding with edoxaban in gastrointestinal cancer patients,
these data provide important insights that we need to weigh up in
treatment decisions, considering the risk of recurrent VTE, patient
preference regarding drug administration and the possible severity of
bleeding."

The Hokusai-VTE CANCER study was conducted in 1,050 patients with
cancer-associated VTE, and included a broad spectrum of cancer
patients, representative of those seen in clinical practice. Most
patients had solid tumours originating from the gastrointestinal
tract, lung or breast that were metastatic in over half of the cases
at randomisation.[1]

VTE is a common complication in cancer patients and is a leading
cause of morbidity and mortality.[1] It is estimated that 3-15% of
patients with active cancer suffer from VTE, depending on cancer
type,[1] and that the prevalence of VTE in hospitalised patients is
increasing.[2] VTE can interrupt cancer treatment, which could have a
negative impact on patient outcomes.[3]

The new findings reported in Thrombosis and Haemostasis are
further supported by a paper published in Expert Opinion on
Pharmacotherapy, which reviewed expert opinion and guidance in
cancer-associated thrombosis (CAT).[4] The review noted that edoxaban
is non-inferior to dalteparin, with a trend towards fewer recurrent
VTE events, but with more major bleeding events.[4] It was cited that
similar findings to these were reported with rivaroxaban, though the
study was not powered to allow definitive conclusions and no
information was reported on concomitant cancer drugs.[4] The review
states that The National Comprehensive Cancer Network (NCCN) (US)
recently updated their guidelines giving edoxaban a level 1
recommendation for treatment of patients with CAT, indicating a
uniform consensus that edoxaban is appropriate based on a high level
of evidence.[4] By comparison, other non-vitamin K oral
anticoagulants (NOACs; apixaban, rivaroxaban and dabigatran) received
a level 2A recommendation, indicating that the consensus is based on
lower level evidence.[4],[5] The review concluded that NOACs are an
alternative to low molecular weight heparin (LMWH) for the treatment
of CAT for the majority of patients with active cancer.[4]

The Scientific and Standardization Committee of the ISTH also
issued guidance recently, suggesting NOACs for the treatment of
cancer-associated VTE. Reporting that only two NOACs, edoxaban and
rivaroxaban, have been compared to LMWH in randomised clinical
trials, their use was recommended in patients with a low risk of
bleeding and no drug-drug interactions with current system
therapy.[6]

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, Canada, Germany, the U.K.,
Switzerland, Ireland, the Netherlands, Italy, Spain, Belgium,
Austria, Portugal, 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 the Hokusai-VTE CANCER study

Hokusai-VTE CANCER is a multinational, prospective, randomized,
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.[7],[8],[9] 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.[7],[8],[9]
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.[7],[8],[9] The study enrolled
1,050 patients across 13 countries in North America, Europe,
Australia and New Zealand.[8],[9] Patients were randomized 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.[7],[8],[9]

For more information please visit:
https://www.clinicaltrials.gov/ct2/show/NCT02073682.[10]

About EDOSURE - Edoxaban Clinical Research Program

More than 10 studies, more than 100,000 patients worldwide

Daiichi Sankyo is committed to expanding scientific knowledge
about edoxaban, as demonstrated through our research programs
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 program, EDOSURE, which is comprised of more than
10 RCTs (randomized, controlled trials), registries and
non-interventional studies, including completed, ongoing and future
research. The goal is to generate new 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)

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 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

Through EDOSURE, 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. Kraaijpoel N et al. Clinical Impact of Bleeding in
Cancer-Associated Venous Thromboembolism: Results from the
Hokusai VTE Cancer Study. Thrombosis and Haemostasis. 2018
Aug;118(8):1439-1449. DOI: 10.1055/s-0038-1667001. Epub 2018 Jul
30.
2. Khorana AA, et al. Frequency, risk factors, and trends for venous
thromboembolism among hospitalized cancer patients. Cancer.
2007;110(10):2339-2346.
3. Hisada Y, et al. Venous Thrombosis and Cancer: from Mouse Models
to Clinical Trials. Journal of Thrombosis and Haemostasis.
2015;13(8):1372-1382.
4. Imberti D et al. Antithrombotic therapy for venous
thromboembolism in patients with cancer: expert guidance. Expert
Opinion on Pharmacotherapy. 2018 Jul 16:1-9. DOI:
10.1080/14656566.2018.1496238. [Epub ahead of print]
5. National Comprehensive Cancer Network. NCCN Clinical Practice
Guidelines in Oncology (NCCN Guidelines). Cancer-Associated
Venous Thromboembolic Disease. Version 1.2018 - March 22, 2018.
6. Khorana AA, et al. Role of direct oral anticoagulants in the
treatment of cancer-associated venous thromboembolism: guidance
from the SSC of the ISTH. Journal of Thrombosis and Haemostasis,
16: 1-4. DOI:10.1111/jth.14219.
7. 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.
8. 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.
9. Raskob GE, van Es N, Verhamme, P, Carrier M, Di Nisio M, Garcia
D, Grosso MA, Kakkar AJ, Kovacs MJ, Mercuri MF, Meyer G, Segers
A, Shi M, Wang TF, Zhang G, Zwicker JI, Weitz JI, Buller HR.
Edoxaban for the treatment of cancer-associated thromboembolism.
N Engl J Med. 2018 Feb 15;378(7):615-624.
10. ClinicalTrials.gov. Cancer Venous Thromboembolism (VTE).
Available at: https://clinicaltrials.gov/ct2/show/NCT02073682.
[Last accessed: July 2018].

Contact

Lydia Worms (Europe)

Daiichi Sankyo Europe GmbH

Edoxaban Communications & Product PR Europe

+49-(89)-7808751

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