Daiichi Sankyo Presents Positive Results of the First Randomised, Controlled Trial of Uninterrupted Oral, Once-daily LIX

MUNICH, March 18, 2019 /PRNewswire/ --

-- ELIMINATE-AF is the first set of data presented in 2019 from the Edoxaban Clinical Research Programme, which will deliver new evidence to support the use of edoxaban in clinical practice -- Late-breaking data presented at EHRA 2019, the annual congress of the European Heart Rhythm Association, shows ELIMINATE-AF met primary efficacy and safety objectives, demonstrating low thromboembolic and bleeding event rates(1) -- ELIMINATE-AF provides evidence that uninterrupted LIXIANA()? (edoxaban) treatment represents an alternative to continuous anticoagulation with VKA in patients undergoing catheter ablation of AF

Daiichi Sankyo Company, Limited (hereafter, "Daiichi Sankyo") today announced results from ELIMINATE-AF, a prospective, randomised, open label, blinded endpoint evaluation (PROBE) design study assessing the safety and efficacy of uninterrupted oral, once-daily edoxaban (known by the brand name LIXIANA()?) 60 mg versus uninterrupted vitamin K antagonists (VKA) in atrial fibrillation (AF) patients undergoing catheter ablation. The study showed the uninterrupted anticoagulation regimen with edoxaban in patients undergoing catheter ablation resulted in low event rates for both thromboembolic and bleeding events.(1) The data were presented today during a late-breaker session at EHRA 2019, the annual congress of the European Heart Rhythm Association, in Lisbon, Portugal.

The primary efficacy objective of ELIMINATE-AF was to compare descriptively the time to first all-cause death, stroke, or International Society on Thrombosis and Haemostasis (ISTH)-defined major bleeding, assessed in the per-protocol population from the end of ablation procedure to the end of treatment. The incidence of the primary endpoint was 0.3% (1/316) in the edoxaban group and 2.0% (2/101) in the VKA group (HR 0.16; 95% CI 0.02, 1.73). The event rate was low and similar in both treatment arms; most events were procedure -related. All three events were major bleedings, and there were no deaths in the study. Edoxaban adherence was excellent (>97%) and VKA treatment was well managed.(1)

The primary safety objective was to compare descriptively the incidence of ISTH-defined major bleeding in the edoxaban group against the VKA group in the period from date of first intake of study medication to end of treatment/Day 90. The primary safety endpoint in the mITT (modified Intent to Treat) population occurred in 2.5% (10/405) in the edoxaban group and 1.5% (3/197) in the VKA group (HR 1.68; 95 CI 0.46, 6.07).

"Catheter ablation is a common and effective procedure for rhythm control in patients with symptomatic AF. However, the procedure is associated with a significant thromboembolic risk during and shortly after the procedure, requiring systemic anticoagulation before, during, and after ablation," said Stefan Hohnloser, MD, Professor of Medicine and Cardiology, Head, Department of Electrophysiology, Johann Wolfgang Goethe University in Frankfurt, Germany, and principal study investigator. "These results provide evidence that uninterrupted edoxaban treatment represents an alternative to continuous anticoagulation with VKA in patients undergoing catheter ablation of AF. This is significant for this complex patient population and physicians because the management of anticoagulation around ablation is much easier with once-daily edoxaban, with low potential of interaction with concomitant drugs."

Until recently, there has been a lack of data to support the uninterrupted peri-procedural use of non-VKA, oral anticoagulants (NOACs) during AF ablation. ELIMINATE-AF was the first randomised controlled trial on the use of edoxaban for catheter ablation of AF.

"We are encouraged by these results, which represent an important potential advancement in the way we manage thromboembolic risk surrounding catheter ablation," said Hans Lanz, MD, Vice President, Head, Global Medical Affairs Edoxaban, Daiichi Sankyo Europe GmbH. "ELIMINATE-AF will help define the role of uninterrupted therapy with edoxaban in the clinical setting of catheter ablation of AF. These results are the first of a broad set of data to be presented in 2019 supporting the use of edoxaban in specific clinical situations and the real-world setting."

ELIMINATE-AF is one of more than 10 randomised, controlled trials (RCTs), registries and non-interventional studies that comprise the Edoxaban Clinical Research Programme. More than 100,000 patients worldwide are expected to participate in the Edoxaban Clinical Research Programme studies, the goal of which is to generate new clinical and real-world data regarding its use in AF and venous thromboembolism (VTE) populations, providing physicians and patients worldwide with greater treatment confidence.

About ELIMINATE-AF

EvaLuatIon of Edoxaban coMpared with VKA INsubjects undergoing cAThEter ablation of non-valvular Atrial Fibrillation (ELIMINATE-AF) was a prospective, randomised, open-label, blinded endpoint evaluation, parallel-group phase 3b study to evaluate the efficacy and safety of once-daily edoxaban against a vitamin K antagonist in AF patients undergoing catheter ablation of AF. The primary objective was to descriptively compare the incidence of the composite of all-cause death, stroke (ischemic, hemorrhagic, or undetermined) and major bleeding (ISTH definition) in the edoxaban group against the vitamin K antagonist group in the period from the end of the catheter ablation procedure to Day 90/end-of-treatment (EOT). The primary safety objective was to descriptively compare the incidence of major bleeding (ISTH definition) in the edoxaban group against the VKA group in the period from date of first intake of study medication to Day 90/EOT. Approximately 600 patients were enrolled in ELIMINATE-AF from more than 70 clinical sites across Europe, Canada and Asia. Patients were randomised (2:1) to receive edoxaban or VKA for 21 to 28 days pre- and 90 days post-ablation period.(2 )

About Atrial Fibrillation

AF is a condition where the heart beats irregularly and rapidly. When this happens, blood can pool and thicken in the chambers of the heart causing an increased risk of blood clots. These blood clots can break off and travel through the blood stream to the brain (or sometimes to another part of the body), where they have the potential to cause a stroke.(3)

AF is the most common type of heart rhythm disorder and is associated with substantial morbidity and mortality.(4) More than six million Europeans are diagnosed with AF, and this figure is expected to at least double over the next 50 years.(5,6 )Compared to those without AF, people with the arrhythmia have a 3-5 times higher risk of stroke.(7) One in five of all strokes are a result of AF.(8)

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 by Daiichi Sankyo and its partners in more than 20 countries around the world.

About the Edoxaban Clinical Research Programme

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

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