Phase 3 Data Show Daiichi Sankyo's Once-Daily Edoxaban Lowered Incidence of VTE Recurrence and Clinically Relevant Bleeding

Phase 3 Data Show Daiichi Sankyo's Once-Daily Edoxaban Lowered Incidence of 
VTE Recurrence and Clinically Relevant Bleeding Compared to Warfarin in a 
Large Subgroup of Patients with Cancer 
- VTE patients with cancer treated with once-daily edoxaban had a numerically 
lower incidence of recurrent VTE and a 36% lower risk of clinically relevant 
bleeding compared to warfarin in a subgroup analysis of the phase 3 
Hokusai-VTE study(1) 
- In general, the annual incidence of VTE is as high as 20% in cancer patients 
and contributes to increased risk of mortality(2) 
- Results in this subgroup analysis are consistent with the overall phase 3 
Hokusai-VTE results previously reported(1,3) 
- This analysis of VTE patients with cancer was presented at the 2013 American 
Society of Hematology Annual Meeting and Exposition 
NEW ORLEANS and TOKYO, Dec. 9, 2013 /CNW/ - Daiichi Sankyo Company, Limited 
(hereafter, Daiichi Sankyo) today announced results of a prespecified subgroup 
analysis of 771 cancer patients enrolled in the phase 3 Hokusai-VTE study. 
Patients with either a history of cancer (n=563) or with active cancer (n=208) 
treated with the once-daily factor Xa-inhibitor edoxaban had a numerically 
lower incidence of recurrent symptomatic venous thromboembolism (VTE) compared 
to warfarin (3.7% vs. 7.1%, respectively; hazard ratio [HR], 0.53; 95% 
confidence interval [CI], 0.28 to 1.00). Once-daily edoxaban also had a lower 
incidence of clinically relevant bleeding (major or non-major) compared to 
warfarin in cancer patients (12.4% vs. 18.8%, respectively; HR, 0.64; 95% CI, 
0.45 to 0.92).(1) These findings are consistent with the results from the 
wider study population of 8,292 patients, which found once-daily edoxaban met 
the primary efficacy endpoint of non-inferiority for the treatment and 
prevention of VTE and superiority for the pre-specified principal safety 
outcome of clinically relevant bleeding compared to warfarin.(3) The data from 
this subgroup analysis of the phase 3 Hokusai-VTE study were presented at the 
2013 American Society of Hematology Annual Meeting and Exposition in New 
Orleans. 
"VTE is a common complication in cancer patients, and cancer patients with VTE 
are at higher risk of recurrence, so we are pleased that the subgroup analysis 
found that patients treated with edoxaban had a numerically lower incidence of 
VTE recurrence and clinically relevant bleeding compared to warfarin," said 
Gary Raskob, PhD, Dean of the College of Public Health, Professor, 
Epidemiology and Medicine University of Oklahoma Health Sciences Center in 
Oklahoma City, Oklahoma and member of the Hokusai-VTE steering committee. 
"These findings provide us with insights about the potential benefit of 
edoxaban administered once-daily compared to warfarin for the treatment and 
prevention of recurrent symptomatic VTE in cancer patients." 
"VTE is a major cause of morbidity and mortality in patients with cancer, with 
an annual incidence that can be as high as 20% depending on the cancer type, 
background risk, and time since diagnosis,"(2,4) said Harry Buller, MD, PhD, 
Professor of Internal Medicine, Chairman of the Department of Vascular 
Medicine at the Academic Medical Center in Amsterdam, The Netherlands and 
Chairman of the Hokusai-VTE steering committee. "A promising finding was the 
sizeable reduction in recurrent symptomatic VTE among cancer patients who were 
treated with once-daily edoxaban." 
In the subset of 208 patients with active cancer, once-daily edoxaban had a 
rate of VTE recurrence of 3.7% compared to 7.1% for warfarin (HR, 0.55; 95% 
CI, 0.16 to 1.85) and an incidence of clinically relevant bleeding of 18.3% 
compared to 25.3% for warfarin (HR, 0.72; 95% CI, 0.40 to 1.30).(1) 
"Our global Hokusai-VTE study of once-daily edoxaban included a broad range of 
patients and we recognize that VTE can be a common complication of cancer, so 
it´s not surprising to see that 9.3% of patients enrolled had active cancer 
or a history of cancer," said Glenn Gormley, MD, PhD, Senior Executive Officer 
and Global Head of Research and Development, Daiichi Sankyo Co., Ltd. and 
President and CEO of Daiichi Sankyo, Inc. in the United States. "Daiichi 
Sankyo is committed to help clinicians understand potential treatment 
strategies for diverse patient populations with VTE." 
About Hokusai-VTE  Hokusai-VTE was a global, event-driven, randomized, 
double-blind, 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 deep vein thrombosis (DVT), pulmonary 
embolism (PE), or both. The Hokusai-VTE study was designed to reflect clinical 
practice using a flexible treatment duration of three to 12 months, including 
initial use of heparin, the proven global standard of care, in both arms, in a 
broad spectrum of VTE patients, including those with cancer.(3) 
The full results were presented at the ESC Congress 2013 in Amsterdam and 
published in the New England Journal of Medicine, demonstrating that edoxaban 
met the primary efficacy endpoint of non-inferiority, with a numerically lower 
incidence of recurrent symptomatic VTE compared to warfarin (3.2% vs. 3.5%, 
respectively) (HR, 0.89; 95% CI, 0.70 to 1.13; p<0.001 for non-inferiority) 
following initial use of heparin in both arms. Recurrent symptomatic VTE was 
defined as the composite of recurrent symptomatic DVT, non-fatal symptomatic 
PE and fatal PE in patients during the 12-month study period. Once-daily 
edoxaban was also found to be superior to warfarin for the pre-specified 
principal safety outcome of clinically relevant bleeding (8.5% vs. 10.3%, 
respectively) (HR, 0.81; 95% CI, 0.71 to 0.94; p=0.004 for superiority) 
occurring during or within three days of interrupting or stopping study 
treatment.(3) 
The Hokusai-VTE study included a prespecified subgroup analysis of patients 
with either a history of cancer (n=563) or with active cancer (n=208) if long 
term low molecular weight heparin (LMWH) was not planned due to availability, 
physician judgment or patient preference. The trial excluded patients with 
active cancer for whom long term treatment with LMWH was anticipated.(3) 
The study is named after the famous Japanese artist and painter Katsushika 
Hokusai. 
Venous Thromboembolism in Cancer Patients VTE is an umbrella term for two 
conditions, DVT and PE. DVT is a blood clot found anywhere in the deep veins 
of the legs, while PE occurs when part of a clot detaches and lodges in the 
pulmonary arteries, causing a potentially fatal condition.(5) 
In cancer patients, there is a significantly increased risk of VTE compared to 
the general population due to proteins released by malignant tumors that 
promote coagulation.(6) Studies have suggested that patients with cancers of 
the pancreas, lung, stomach and adenocarcinomas of unknown primary origin are 
at the highest risk of VTE due to the release of mucin, a protein commonly 
found in these types of cancers that can contribute to coagulation through the 
aggregation of platelets.(7,8) Certain anticancer therapies, such as 
chemotherapy, immunomodulatory agents and antiangiogenic agents also increase 
the risk of VTE in this patient population.(7) 
In the general population VTE is a major cause of morbidity and mortality 
worldwide with an annual incidence of approximately one per 1,000 in developed 
countries, including an estimated 430,000 PE events, 680,000 DVT events and 
540,000 deaths each year in the EU.(9,10) In the U.S., it is currently 
estimated that more than 950,000 VTE events and approximately 300,000 VTE 
related deaths occur each year.(11,12) In patients with cancer who develop 
VTE, there is a four- to eight-fold higher risk of dying after an acute 
thrombotic event than in patients without cancer.(7) Additionally, patients 
with cancer and VTE have a lower survival rate than those without VTE.(7) 
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.(13 )The global edoxaban 
clinical trial program includes two phase 3 clinical studies, Hokusai-VTE and 
ENGAGE AF-TIMI 48 (Effective aNticoaGulation with Factor XA Next GEneration in 
Atrial Fibrillation). The results from these trials will form the basis of New 
Drug Applications for edoxaban for two potential indications, the treatment 
and prevention of recurrence of venous thromboembolism (VTE) in patients with 
deep vein thrombosis (DVT) and/or pulmonary embolism (PE), and for the 
prevention of stroke and systemic embolic events (SEE) in patients with 
non-valvular atrial fibrillation, respectively.(3,14) 
Edoxaban is currently approved only in Japan, since April 2011, for the 
prevention of VTE after major orthopedic surgery, and was launched in July 
2011 under the brand name Lixiana(®). Elsewhere, including Europe and the 
U.S., edoxaban is currently in phase 3 clinical development and has not been 
approved in any indication.(15) 
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, 
hyperlipidemia, and bacterial infections, the Group is engaged in the 
development of treatments for thrombotic disorders and focused on the 
discovery of novel oncology and cardiovascular-metabolic therapies. 
Furthermore, the Daiichi Sankyo Group has created a "Hybrid Business Model," 
which will respond to market and customer diversity and optimize growth 
opportunities across the value chain. For more information, please visit: 
www.daiichisankyo.com. 
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|Global Media                                                                                                            
                           |US Media                                                                                 
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|Michaela Paudler-Debus, PhD                                                                                             
                           |Alyssa Dargento                                                                          
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|Daiichi Sankyo Europe                                                                                                   
                           |Daiichi Sankyo, Inc.                                                                     
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|michaela.paudler-debus@daiichi-sankyo.eu|adargento@dsi.com|
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|+49 89 7808 685 (office)                                                                                                
                           |+1 973 944 2913 (office)                                                                 
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|+49 176 11780966 (mobile)                                                                                               
                           |+1 973 727 1604 (mobile)                                                                 
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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. Raskob, GE et al. Edoxaban for long-term treatment Of venous 


     thromboembolism in cancer patients. Presented at the 2013 American
     Society of Hematology Annual Meeting and Exposition. Abstract


 number 211.
  2. Ay, C, et al. Prediction of venous thromboembolism in cancer 
 patients. Blood 2010; 116:5377-5382.
  3. Buller, H et al. Edoxaban versus warfarin for the treatment of 
 symptomatic venous thromboembolism. N Engl J Med 2013.
  4. Lyman, GH et al. American Society of Clinical Oncology guideline: 


     recommendations for venous thromboembolism prophylaxis and
     treatment in patients with cancer. Journal of Clinical Oncology


 2007;25:5490-5505.
  5. Van Beek, E et al. Deep vein thrombosis and pulmonary embolism. 
 New York: John Wiley & Sons, 2009. Print.
  6. Boccaccio, C et al. Genetic link between cancer and thrombosis. J 
 Clin Oncol 27:4827-4833.
  7. Lee, AYY, et al. Venous thromboembolism and cancer: Risks and 
 outcomes. Circulation 2003;107:I-17-I-21.
  8. Wahrenbrock, M et al. Selectin-mucin interactions as a probable 


     molecular explanation for the association of Trousseau syndrome
     with mucinous adenocarcinomas. J Clin Invest 112:853–862


 (2003).
  9. Bramlage P, Pittrow D, Kirch,W. Current concepts for the 
 prevention of venous thromboembolism. Eur J Clin Invest 2005; 35 
 (Suppl. 1):4-11.
 10. Cohen A, Agnelli G, Anderson F. Venous thromboembolism (VTE) in 
 Europe. Thromb Haemost 2007; 98: 756–764.
 11. Deitelzweig S, Lin J, Johnson BH, Schulman KL. Prevalence of 
 venous thromboembolism in the USA: now and future. Thromb Haemost 
 2009;7 (Suppl. 2):207-8 (abstract OC-WE-018).
 12. Heit JA, Cohen AT, Anderson FAJ, on behalf of the VTE Impact 


     Assessment Group. Estimated annual number of incident and
     recurrent, non-fatal and fatal venous thromboembolism (VTE) events


 in the US. ASH Annual Meeting Abstracts. 106:910. 2005.
 13. Ogata, K et al. Clinical safety, tolerability, pharmacokinetics, 
 and pharmacodynamics of the novel factor Xa inhibitor edoxaban in 
 healthy volunteers. J Clin Pharmacol 2010;50:743-753.
 14. Giugliano, RP et al. Edoxaban versus warfarin in patients with 
 atrial fibrillation. N Engl J Med 2013.
 15. Daiichi Sankyo press release - Daiichi Sankyo launches LIXIANA® 


     (edoxaban), a direct oral factor Xa inhibitor, in Japan for the
     prevention of venous thromboembolism after major orthopaedic
     surgery. 19 July 2011. Available at:
     http://www.daiichisankyo.com/news/detail/004123.html.
     [Last accessed: December 2013].



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