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

MUNICH, Aug. 6, 2018 /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_-_Product_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

SOURCE Daiichi Sankyo Company, Limited