BASKING RIDGE, N.J.,
Dec. 12, 2017 /PRNewswire/
-- Daiichi Sankyo, Inc., (hereafter, Daiichi Sankyo), today
announced results from the Hokusai-VTE CANCER study evaluating oral
edoxaban (known by the brand names SAVAYSA® in the U.S.
and LIXIANA® outside the U.S.), and found that edoxaban
is non-inferior to subcutaneous injectable LMWH dalteparin for the
treatment of cancer-associated VTE or major bleeding2,3.
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.
The Hokusai-VTE CANCER 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
arm2,3.
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
randomization2,3.
"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 chemotherapy4. The treatment of
cancer-associated VTE is challenging because these patients are at
increased risk of both recurrent VTE and major
bleeding2. The occurrence of VTE increases the risk of
death 2-6-fold in cancer patients4 and can interrupt
cancer treatment5.
"Data from the Hokusai-VTE CANCER study will continue to add to
the growing body of knowledge in the Edoxaban Clinical Research
Program, which provides key insights into the potential effects of
edoxaban in VTE and AF patients," said Hans
J. Lanz, MD, Vice President, Global Medical Affairs, Daiichi
Sankyo.
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
cancer1,2,3. 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 cancer1,2,3. 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 death1,2,3. The study enrolled 1,050
patients across 13 countries in North
America, Europe,
Australia and New Zealand2,3. 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
study1,2,3.
For more information please visit:
https://www.clinicaltrials.gov/ct2/show/NCT020736826.
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
well7. PE occurs when part of a clot detaches and lodges
in the pulmonary arteries, causing a potentially fatal
condition8.
VTE is a major cause of morbidity and mortality9. In
the U.S., it is estimated that more than 950,000 VTE events and
approximately 300,000 VTE related deaths occur each
year10,11. There is a high rate of recurrence after a
first VTE event, which is reduced with anticoagulant treatment.
Without anticoagulant treatment, approximately half of patients who
experience an initial VTE event have recurrent VTE within three
months11.
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 10,11. Patients
with cancer have multiple risk factors for VTE and the risk of VTE
events increases in patients with cancer receiving chemotherapy
15. In addition, patients with cancer and VTE have a
lower survival rate than those without VTE15.
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.
About Edoxaban Clinical Research Program
(ECRP)
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 thrombo-embolism (VTE). The edoxaban
clinical research program includes multiple RCTs (randomized,
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 program, 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 SAVAYSA® (edoxaban)
Edoxaban, also
known as SAVAYSA in the U.S., is an oral, once-daily anticoagulant
that specifically inhibits factor Xa, which is an important factor
in the coagulation system that leads to blood clotting. The global
edoxaban clinical trial program included two phase 3 clinical
studies, Hokusai-VTE and ENGAGE AF-TIMI 48, with nearly 30,000
patients combined. The results from these trials formed the basis
of the regulatory filing in the U.S. for SAVAYSA for the reduction
in risk of stroke and SE in patients with NVAF, as well as for the
treatment of DVT and PE following 5-10 days of initial therapy with
a parenteral anticoagulant. According to the U.S. label, SAVAYSA
should not be used in NVAF patients with creatinine clearance
(CrCL) levels greater than 95 mL/min because in that population
there is an increased risk of ischemic stroke compared to
warfarin.
Indication
SAVAYSA® (edoxaban) is indicated
to reduce the risk of stroke and systemic embolism (SE) in patients
with nonvalvular atrial fibrillation (NVAF). SAVAYSA should not be
used in patients with creatinine clearance (CrCl) >95 mL/min
because of an increased risk of ischemic stroke compared to
warfarin.
SAVAYSA is indicated for the treatment of deep vein thrombosis
(DVT) and pulmonary embolism (PE) following 5 to 10 days of initial
therapy with a parenteral anticoagulant.
IMPORTANT SAFETY INFORMATION FOR SAVAYSA
BOXED WARNINGS
- REDUCED EFFICACY IN NVAF PATIENTS WITH CRCL >95
ML/MIN
SAVAYSA should not be used in patients with CrCl >95
mL/min. In the ENGAGE AF-TIMI 48 study, NVAF patients with CrCl
>95 mL/min had an increased rate of ischemic stroke with SAVAYSA
60 mg once daily compared to patients treated with warfarin. In
these patients another anticoagulant should be used.
- PREMATURE DISCONTINUATION OF SAVAYSA INCREASES THE RISK OF
ISCHEMIC EVENTS
Premature discontinuation of any oral anticoagulant in the
absence of adequate alternative anticoagulation increases the risk
of ischemic events. If SAVAYSA is discontinued for a reason other
than pathological bleeding or completion of a course of therapy,
consider coverage with another anticoagulant as described in the
transition guidance in the Prescribing Information.
- SPINAL/EPIDURAL HEMATOMA
-
- Epidural or spinal hematomas may occur in patients treated
with SAVAYSA who are receiving neuraxial anesthesia or undergoing
spinal puncture. These hematomas may result in long-term or
permanent paralysis. Consider these risks when scheduling patients
for spinal procedures
- Factors that can increase the risk of developing epidural or
spinal hematomas in these patients include: use of indwelling
epidural catheters; concomitant use of other drugs that affect
hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs),
platelet inhibitors, other anticoagulants; a history of traumatic
or repeated epidural or spinal punctures; a history of spinal
deformity or spinal surgery
- Optimal timing between the administration of SAVAYSA and
neuraxial procedures is not known
Monitor patients frequently for signs and symptoms of
neurological impairment. If neurological compromise is noted,
urgent treatment is necessary. Consider the benefits and risks
before neuraxial intervention in patients anticoagulated or to be
anticoagulated.
CONTRAINDICATIONS
SAVAYSA is contraindicated in
patients with active pathological bleeding.
WARNINGS AND PRECAUTIONS
Bleeding
Risk
SAVAYSA increases the risk of bleeding and can cause
serious and potentially fatal bleeding. Promptly evaluate any signs
or symptoms of blood loss. Discontinue SAVAYSA in patients with
active pathological bleeding. Concomitant use of drugs affecting
hemostasis may increase the risk of bleeding. These include aspirin
and other antiplatelet agents, other antithrombotic agents,
fibrinolytic therapy, chronic use of nonsteroidal anti-inflammatory
drugs (NSAIDs), selective serotonin reuptake inhibitors (SSRIs),
and serotonin norepinephrine reuptake inhibitors (SNRIs). There is
no established way to reverse the anticoagulant effects of SAVAYSA,
which can be expected to persist for approximately 24 hours after
the last dose. The anticoagulant effect of SAVAYSA cannot be
reliably monitored with standard laboratory testing. A specific
reversal agent for edoxaban is not available. Hemodialysis does not
significantly contribute to edoxaban clearance. Protamine sulfate,
vitamin K, and tranexamic acid are not expected to reverse its
anticoagulant activity.
Mechanical Heart Valves or Moderate to Severe Mitral
Stenosis
The safety and efficacy of SAVAYSA has not been
studied in patients with mechanical heart valves or moderate to
severe mitral stenosis. SAVAYSA is not recommended in these
patients.
ADVERSE REACTIONS
- NVAF: The most common adverse reactions (≥5%) are
bleeding and anemia
- DVT/PE: The most common adverse reactions (≥1%) are
bleeding, rash, abnormal liver function tests and anemia
DISCONTINUATION FOR SURGERY AND OTHER
INTERVENTIONS
Discontinue SAVAYSA at least 24 hours before
invasive or surgical procedures because of the risk of bleeding.
SAVAYSA can be restarted after the surgical or other procedure as
soon as adequate hemostasis has been established.
DRUG INTERACTIONS
- Anticoagulants, Antiplatelets, and Thrombolytics:
Coadministration of anticoagulants, antiplatelet drugs, and
thrombolytics may increase the risk of bleeding
- P-gp Inducers: Avoid concomitant use of SAVAYSA with
rifampin
- P-gp Inhibitors (DVT/PE only): Coadministration of
certain P-gp inhibitor medications requires a dose reduction of
SAVAYSA to 30 mg once daily
SPECIAL POPULATIONS
- Lactation: Breastfeeding not recommended
- Pregnancy: Insufficient data to determine drug-associated risks
for adverse developmental outcomes
- Impaired renal function (CrCl 15 to 50 mL/min): Reduce SAVAYSA
dose to 30 mg once daily
- Moderate or severe hepatic impairment: Not recommended
Please see full Prescribing Information, including Boxed
WARNINGS and Medication Guide.
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: www.daiichisankyo.com.
Contact
Kimberly
Wix
Daiichi Sankyo, Inc.
Senior Director, Public Affairs
+1 973 944 2338
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
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 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
- 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.
View original
content:http://www.prnewswire.com/news-releases/once-daily-oral-savaysa-edoxaban-met-primary-endpoint-in-investigational-hokusai-vte-cancer-study-300569859.html
SOURCE Daiichi Sankyo, Inc.