The Swissmedic, the regulatory authority of Switzerland, has granted approval of Daiichi Sankyo's Lixiana (edoxaban), an oral, once-daily selective factor Xa inhibitor, for the prevention of stroke and systemic embolism (SE) in adult patients with non-valvular atrial fibrillation (NVAF).
Simultaneously, Lixiana has received marketing authorisation in Switzerland for the treatment of adult patients with venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), following previous treatment with fractionated or unfractionated heparin for five days, as well as for the prevention of recurrent VTE.
“Lixiana is an important new anticoagulant for physicians and their patients with NVAF and VTE,” said Glenn Gormley, MD, PhD, senior executive officer and global head of R&D, Daiichi Sankyo Company, Limited and executive chairman and president, Daiichi Sankyo, Inc.“The approval of Lixiana in Switzerland marks Daiichi Sankyo’s first opportunity to make once-daily edoxaban available in a European country, and illustrates the Company’s commitment to providing new treatment options to patients with cardiovascular diseases with significant unmet needs.”
The approved indications in Switzerland for Lixiana are based on data from the phase 3 ENGAGE AF-TIMI 48 and Hokusai-VTE studies, the largest and longest single comparative global trials of a novel oral anticoagulant in patients with NVAF or acute VTE, involving 21,105 and 8,292 patients, respectively.
In the ENGAGE AF-TIMI 48 study, once-daily edoxaban 60 mg demonstrated non-inferiority to warfarin, for the primary efficacy endpoint of occurrence of stroke or SE in patients with NVAF (1.18% vs. 1.50% per year, respectively; hazard ratio [HR], 0.79; 97.5% confidence interval [CI], 0.63 to 0.99, p<0.001). In addition, once-daily edoxaban 60 mg demonstrated a significant 20% risk reduction of major bleeding in patients with NVAF compared to warfarin (2.75% vs. 3.43% per year, respectively; HR, 0.80; 95% CI, 0.71 to 0.91, p<0.001).
In the Hokusai-VTE study, once-daily edoxaban 60 mg was non-inferior to warfarin for the primary efficacy endpoint of recurrence of symptomatic VTE (3.2% vs. 3.5% of patients, respectively; HR, 0.89; 95% CI, 0.70 to 1.13, p<0.001). In addition, edoxaban demonstrated a significant 19% risk reduction of clinically relevant bleeding in patients with VTE compared to warfarin (8.5% vs. 10.3% of patients, respectively; HR, 0.81; 95% CI, 0.71 to 0.94, p=0.004).
Atrial fibrillation (AF) is the most common type of heart rhythm disorder, and is associated with substantial morbidity and mortality. More than 80,000 people in Switzerland suffer from AF, and true prevalence may be higher as up to one third of AF patients do not present with symptoms and go undiagnosed. More than six million Europeans are diagnosed with AF, and this figure is expected to at least double over the next 50 years. One in five of all strokes are as a result of AF.
VTE is a major cause of morbidity and mortality. VTE is a major health problem in Europe, with over one million VTE events or deaths per year (France, Germany, Italy, Spain, Sweden, UK), including more than 370,000 VTE-related deaths.
In Switzerland, Lixiana (edoxaban) is indicated for the prevention of stroke and SE in adult patients with NVAF, and for the treatment of adult patients with VTE, including DVT and PE, following previous treatment with fractionated or unfractionated heparin for five days, as well as for the prevention of recurrent VTE.1 The recommended dose of Lixiana is 60 mg once-daily, with a dose reduction to 30 mg once-daily in patients with moderate or severe renal impairment (creatinine clearance [CrCl] 15-50 mL/min), body weight = 60 kg, or concomitant use of certain P-glycoprotein (P-gp) inhibitors (ciclosporin, dronedarone, erythromycin, ketoconazole, quinidine or verapamil).
Edoxaban is currently marketed in Japan and the United States. In the EU and other countries, regulatory review is ongoing.
ENGAGE AF-TIMI 48 (Effective aNticoaGulation with factor xA next GEneration in Atrial Fibrillation) was a three-arm, randomized, 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 centers 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) once-daily, with warfarin in patients with NVAF for a median of 2.8 years follow-up. 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 largest and 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.
Hokusai-VTE was a global, event-driven, randomized, double-blind, double-dummy, 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 DVT, PE or both. The Hokusai-VTE study was designed to reflect clinical practice using a flexible treatment duration of 3-12 months in a broad spectrum of VTE patients, including initial use of parenteral anticoagulant (heparin) for 5-10 days, the proven global standard of care. Patients were randomized to receive edoxaban 60 mg once-daily (dose reduced to 30 mg for CrCL 30 to 50 mL/min, body weight of 60 kg or less, or certain p-glycoprotein inhibitor use) or the comparator, warfarin, following initial open-label enoxaparin or unfractionated heparin therapy. In the comparator arm, patients received initial heparin therapy concurrently with warfarin, titrated to a target INR of 2.0 to 3.0, followed by warfarin alone. The treatment duration was from 3 months and up to a maximum of one year. The duration of study treatment was determined by the investigator based on the patient’s clinical features. The full results were presented at the ESC Congress 2013 in Amsterdam and published in the New England Journal of Medicine.
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