Products

* On June 25, 2015, Daiichi Sankyo announced that the European Commission (EC) has granted Marketing Authorisation for Lixiana® (edoxaban), an oral, once-daily selective factor Xa-inhibitor, for the prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation (NVAF) with one or more risk factors, such as congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischaemic attack (TIA) as well as for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults. The EC approval is based on two phase 3 clinical trials, ENGAGE AF-TIMI 48 and Hokusai-VTE, which compared treatment with once-daily Lixiana® to warfarin, a current standard of care for stroke prevention in patients with AF or for the treatment and prevention of VTE. These studies represent the largest single comparative trials of a novel oral anticoagulant in these patient populations, involving 21,105 and 8,292 patients, respectively (see below).

* On April 23, 2015, the European Committee for Medicinal Products for Human Use (CHMP) has recommended approval of once-daily 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) with one or more risk factors. The CHMP also recommended approval of Lixiana® for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults. The two related conditions DVT and PE are collectively referred to as venous thromboembolism (VTE).
The CHMP opinion to approve once-daily edoxaban for the prevention of stroke and SE in adult patients with NVAF with one or more risk factors and for the treatment and prevention of recurrent VTE (DVT and PE) is based on the data of the phase 3 ENGAGE AF-TIMI 48 and Hokusai-VTE studies, respectively.
In the ENGAGE AF-TIMI 48 study, once-daily edoxaban 60 mg demonstrated non-inferiority to well-managed 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).

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 well-managed 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 CrCL 30 to 50 mL/min, body weight of 60 kg or less or certain P-gp 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.2 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-gp 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.3 The full results were presented at the ESC Congress 2013 in Amsterdam and published in the New England Journal of Medicine. Edoxaban is currently marketed in Japan and the U.S. and has received approval in Switzerland. In other countries, regulatory review is ongoing.

 

* On February 9, 2015, Daiichi Sankyo Company announced  that Savaysa™ (edoxaban), an oral, once-daily selective factor Xa-inhibitor, is now commercially available in U.S. pharmacies. The drug was approved by the FDA on January 8, 2015 for the reduction in risk of stroke and systemic embolism (SE) in patients with non-valvular atrial fibrillation (NVAF), as well as for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) following 5-10 days of initial therapy with a parenteral anticoagulant. According to the U.S. label, SAVAYSA should not be used in NVAF patients with creatinine clearance (CrCL) levels greater than 95 mL/min because in that population there is an increased risk of ischemic stroke compared to warfarin.
With the launch of Savaysa™ Daiichi Sankyo has developed resources for physicians and patients to help ensure patients can begin and/or remain on Savaysa™ per physician instructions. The Savaysa™ Savings Plus program will include a reimbursement hotline to assist patients and prescribers who request help understanding the patient’s available coverage. Eligible patients who are prescribed Savaysa™ can enroll in a copay savings program and pay $4 per month through the Savaysa™SAVINGS CARD. Vouchers will also be available to provide patients and doctors a way to try Savaysa™at no cost to see if it is right for the patient. In addition, the Savaysa™ Patient Assistance Program will offer assistance to qualified individuals, providing free product to eligible patients who are prescribed Savaysa™, are uninsured and are unable to identify alternative payment sources.

The approval of Savaysa™ in the U.S. is based on data from the ENGAGE AF-TIMI 48 and Hokusai-VTE trials, involving 21,105 and 8,292 patients, respectively. In ENGAGE AF-TIMI 48, Savaysa™ demonstrated significantly less major bleeding in patients with NVAF in the overall study population (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.70 to 0.91, p<0.001) and was non-inferior to warfarin for the primary efficacy endpoint of stroke or SE. In the indicated NVAF patient population in the U.S. (patients with CrCL ≤ 95 mL/min), the rate of stroke and SE was 1.2% per year for Savaysa™ versus 1.8% per year for warfarin (HR, 0.68; 95% CI, 0.55 to 0.84). Consistent with the overall results,  Savaysa™ also demonstrated fewer major bleeding events compared to warfarin in the indicated NVAF population, as well as lower rates of intracranial hemorrhage (0.5% per year for Savaysa™ and 1.0% per year for warfarin) and fatal bleeding (0.2% per year for Savaysa™ and 0.4% per year for warfarin), but higher rates of major GI bleeding (1.8% per year for Savaysa™ and 1.3% per year for warfarin).In Hokusai-VTE, Savaysa™ was shown to be non-inferior to warfarin for the primary endpoint of symptomatic recurrent VTE, with a significant 19% reduction in clinically relevant bleeding compared to warfarin (8.5% vs. 10.3%; HR, 0.81; 95% CI, 0.71 to 0.94, p=0.004) in patients with DVT or PE, following 5 to 10 days of initial therapy with a parenteral anticoagulant.The most common side effects observed in ENGAGE AF-TIMI 48 and Hokusai-VTE clinical trial participants were bleeding and anemia.2,3 Savaysa™ increases the risk of bleeding and can cause serious and potentially fatal bleeding.

* On January 8, 2015, Daiichi Sankyo announced that the FDA has approved Savaysa™ (edoxaban) Tablets, an oral, once-daily selective factor Xa-inhibitor, to reduce the risk of stroke and systemic embolism (SE) in patients with non-valvular atrial fibrillation (NVAF). In ENGAGE AF-TIMI 48, Savaysa™ was non-inferior to warfarin in the overall study population for the primary efficacy endpoint of stroke or SE. As stated in the U.S. label, Savaysa™ should not be used in NVAF patients with creatinine clearance (CrCL) levels greater than 95 mL/min because in that population there is an increased risk of ischemic stroke compared to warfarin. Patients with CrCL less than or equal to 95 mL/min represented 77% of the patients studied. In those patients, Savaysa™ 60 mg (30 mg dose reduced) reduced the risk of stroke and SE when compared to warfarin (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.55 to 0.84), and the rates of cardiovascular death with Savaysa™ and warfarin were 2.95% per year vs. 3.59% per year, respectively.1 The FDA also approved Savaysa™ for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) following 5-10 days of initial therapy with a parenteral anticoagulant.

* On October 31, 2014, Daiichi Sankyo announced that the FDA Cardiovascular and Renal Drugs Advisory Committee voted 9 to 1 to recommend approval of once-daily Savaysa™ (edoxaban) 60 mg dosing regimen for the reduction in risk of stroke and systemic embolic events (SEE) in patients with non-valvular atrial fibrillation (NVAF). Members of the committee also provided their opinions on the use of Savaysa™. The recommendations were provided after review of the ENGAGE AF-TIMI 48 study results, which were previously communicated at the 2013 American Heart Association Scientific Sessions. The data demonstrated that once-daily edoxaban met the primary efficacy endpoint of non-inferiority compared to warfarin for the reduction in risk of stroke and SEE in patients with NVAF, and demonstrated significantly less major bleeding compared to warfarin, achieving superiority for the principal safety endpoint of major bleeding. Daiichi Sankyo is currently seeking approval from the FDA for the 60 mg dosing regimen of edoxaban (with a dose reduction to 30 mg for patients with known factors such as renal impairment, low body weight or concomitant use of certain P-glycoprotein inhibitors that can potentially increase the risk of bleeding due to expected higher edoxaban exposure) for the reduction in risk of stroke and SEE in patients with NVAF. Daiichi Sankyo is also seeking approval of edoxaban for the treatment and prevention of recurrence of symptomatic venous thromboembolism (VTE) based on the results from the Hokusai-VTE study, which is the single largest comparative trial of a novel oral anticoagulant in this patient population.

* On January 9, 2014,  Daiichi Sankyo has announced that the New Drug Application (NDA) for its investigational, oral, once-daily direct factor Xa-inhibitor Savaysa™ (edoxaban) Tablets has been submitted to the FDA. In the U.S., Daiichi Sankyo is seeking approval for edoxaban for the reduction in risk of stroke and systemic embolic events (SEE) in patients with non-valvular atrial fibrillation (NVAF), as well as for the treatment of deep vein thrombosis (DVT) or pulmonary embolism (PE) and for the prevention of recurrence of symptomatic venous thromboembolism (VTE). The NDA submission is based on the same data used for the MAA submission in Europe (see below).

* On January 7, 2014, Daiichi Sankyo has announced that the Marketing Authorization Application (MAA) for edoxaban has been submitted to the European Medicines Agency (EMA). In Europe, Daiichi Sankyo is seeking approval for edoxaban for the prevention of stroke and systemic embolic events (SEE) in patients with non-valvular atrial fibrillation (NVAF), as well as for the treatment of deep vein thrombosis (DVT) or pulmonary embolism (PE) and prevention of recurrence of symptomatic venous thromboembolism (VTE).

The MAA submission is based on data from an extensive global clinical trial program that compared treatment with once-daily edoxaban to warfarin, a current standard of care for patients with atrial fibrillation (AF) or VTE. The two clinical trials that formed the basis of the submission, ENGAGE AF-TIMI 48 and Hokusai-VTE, are the largest comparative trials of a novel oral anticoagulant in these patient populations, involving 21,105 and 8,292 patients, respectively.

Edoxaban is currently under regulatory review with the Japanese Ministry of Health, Labour and Welfare for NVAF and symptomatic VTE treatment. The drug is currently approved only in Japan, since April 2011, for the prevention of VTE after major orthopaedic surgery, and was launched in July 2011 under the brand name Lixiana®. This first marketing approval for Lixiana® (edoxaban) 15 mg and 30 mg tablets has been given by the Ministry of Health, Labor and Welfare in Japan on April 22, 2011.