LIXIANA® (edoxaban) Shows Reduced Rate of a Variety of Types of Intracranial Haemorrhage Compared to Warfarin in New Sub-analysis Presented at the European Stroke Organisation Conference 2018

• Sub-analysis presented from ENGAGE AF-TIMI 48, the longest single comparative global trial of a non-vitamin K oral anticoagulant (NOAC) in patients with non-valvular atrial fibrillation (NVAF) to date
• Results showed a reduction in both spontaneous and traumatic intracranial haemorrhage (ICH) in patients who took edoxaban, compared to warfarin[1]
• The data is being presented at the European Stroke Organisation Conference (ESOC) 2018, in Gothenburg, Sweden

Daiichi Sankyo Europe GmbH (hereafter, Daiichi Sankyo), today announced new sub-analysis data from the ENGAGE AF-TIMI 48 trial, which demonstrates that patients with atrial fibrillation (AF) treated with edoxaban (known by the brand name LIXIANA®?), for the prevention of stroke or systemic embolic events (SEE), had reduced rates of different types of intracranial haemorrhage (ICH, bleeding inside the skull),[2] compared to those on warfarin.[1] The data was presented at the 4th European Stroke Organisation Congress (ESOC), on 16-18 May, in Gothenburg, Sweden.

Providing insights on the rates of ICH by cause, the sub-analysis showed a 42% reduction in spontaneous ICH (HR 0.58 [0.41-0.81]), which occurred in 97 patients taking either edoxaban or warfarin, and a 62% reduction in traumatic ICH (HR 0.38 [0.23-0.63]), which occurred in 185 patients taking either edoxaban or warfarin, among patients taking edoxaban (60 mg or 30 mg dose reduced, once-daily) compared to warfarin.[1] These results build on the body of evidence supporting the use of edoxaban in clinical practice and follow results from the ENGAGE-AF-TIMI 48 trial, where edoxaban demonstrated non-inferiority to warfarin for the prevention of stroke or SEE in patients with AF, with significant reductions in cardiovascular mortality and major bleeding.[3]

„Non-vitamin K antagonist oral anticoagulants are increasingly used in clinical practice, and it is essential that we continue to expand our understanding of these therapies in specific patient populations, to help inform and optimise care“ said co-author of study Robert P. Giugliano, from the Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA. „Results from the sub-analysis of the ENGAGE AF-TIMI 48 trial suggest that edoxaban offers an advantage over warfarin in patients who need anticoagulation and are at risk of ICH, providing guidance and offering further assurance to physicians regarding its use.“

ICH is a type of bleeding that occurs inside the skull, either within the brain parenchyma or the surrounding meningeal spaces.[2] It can have serious life-long implications for patients, and the mortality rate in ICH is three times that of ischemic stroke.[4]

The sub-analysis provides further insights into outcomes in edoxaban compared to warfarin by ICH subtype, with edoxaban (60 mg or 30 mg dose reduced, once-daily) treated patients having lower rates of intraparenchymal haemorrhage (IPH) (HR 0.55 [95% CI 0.38-0.78]) and subdural hematoma (SDH) (HR 0.36 [0.22-0.58]), and similar rates of subarachnoid haemorrhage (SAH) and ischemic stroke with haemorrhagic transformation (ISHT) (both p>0.05).[1]

„These data provide further insights into the benefits of edoxaban and its use to achieve the best possible outcomes for AF patients,“ said Wolfgang Zierhut, MD, Head of Antithrombotic & Cardiovascular Therapeutic Area, Daiichi Sankyo Europe. „We remain committed to advancing understanding of edoxaban and this data adds to the growing body of evidence supporting its use.“

These latest sub-analysis findings from the ENGAGE AF-TIMI 48 trial align with the ‚2018 European Heart Rhythm Association guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation‘, published in March 2018. The guidelines recommend NOACs over warfarin for the prevention of stroke in eligible AF patients, due to the reduced risk of intracranial and life-threatening bleeds, which has been consistently observed across multiple studies.[5]

About the ENGAGE AF-TIMI 48 Study

ENGAGE AF-TIMI 48 (Effective aNticoaGulation with factor xA next GEneration in Atrial Fibrillation) was a three-arm, randomised, double-blind, double-dummy, global phase 3 clinical trial comparing once-daily edoxaban with warfarin in 21,105 patients with NVAF at moderate-to-high risk of thromboembolic events at 1,393 centres in 46 countries. ENGAGE AF-TIMI 48 compared two edoxaban treatment strategies, a higher dose arm (60 mg or 30 mg dose reduced) once-daily and a lower dose arm (30 mg or 15 mg dose reduced, which is not currently licensed) once-daily, with warfarin in patients with NVAF for a median of 2.8 years. Patients were dose reduced for creatinine clearance (CrCL) 30 to 50 mL/min, body weight of 60 kg or less or certain p-glycoprotein inhibitor use. ENGAGE AF-TIMI 48 represents the longest single comparative global trial with a novel anticoagulant in patients with NVAF performed to date. The full results were presented at the AHA Scientific Sessions 2013 in Dallas and published in the New England Journal of Medicine.[3]

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: h ttp://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_In formation/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. Nelson, S.E. et al. Intracranial haemorrhage in patients with
atrial fibrillation receiving oral anticoagulation with warfarin
or edoxaban. Abstract presented at ESOC Congress 2018.
2. Caceres, A.J., Goldstein, J.N. Intracranial Hemorrhage. Emerg Med
Clin North Am. 2012;30(3):771-794.
3. Giugliano, RP et al. Edoxaban versus Warfarin in Patients with
Atrial Fibrillation. N Engl J Med. 2013;369:2093-104.
4. The Risk of Intracranial Hemorrhage with Anticoagulation in the
Elderly – Estimates of Prevalence and Therapeutic Strategies,
2015. Available at: http://www.acc.org/latest-in-cardiology/articl
es/2015/12/21/12/59/the-risk-of-intracranial-hemorrhage-with-antic
oagulation-in-the-elderly . [last accessed: May 2018].
5. Steffel, J, et al. The 2018 European Heart Rhythm Association
Practical Guide on the use of non-vitamin K antagonist oral
anticoagulants in patients with atrial fibrillation. European
Heart Journal. 2018;21;39(16):1330-1393.

Contact

Lydia Worms (Europe)

Daiichi Sankyo Europe GmbH

Edoxaban Communications & Product PR Europe

+49(89)7808751

EDX/18/0240

Date of preparation: May 2018

Digital press kit: http://www.ots.at/pressemappe/PR62920/aom