Edoxaban, an oral factor Xa inhibitor, is currently being investigated in the pivotal phase III study ENGAGE AF-TIMI 48 (Effective anticoagulation with factor Xa next generation in atrial fibrillation) as a potential new treatment for stroke prevention in patients with atrial fibrillation (AF). The new drug, developed by Daiichi Sankyo, could offer improvements in the management of thromboembolic disease.
“Without anticoagulation treatment these patients have a considerably high risk of having a stroke, approximately five times higher than that of the average population,” said John Camm, professor of clinical cardiology, St George’s University, London, UK, during a press conference organised by Daiichi Sankyo Europe.
“There is a definite need for new and improved oral anticoagulants for stroke prevention in patients with atrial fibrillation,” commented Jeffrey I Weitz, professor of medicine and biochemistry, McMaster University and director of the Henderson Research Centre, Ontario, Canada. “Edoxaban could offer significant improvements in the management of these patients.”
A comprehensive phase I and phase II study programme for edoxaban has already indicated dose-dependent anticoagulation over a range of doses, with no significant dose-related increase in bleeding:
- Edoxaban has a safety and tolerability profile similar to that of warfarin in patients with non-valvular atrial fibrillation. The incidence of major and clinically relevant non-major bleeding events reported in the 30mg and 60mg once daily edoxaban treatment groups was similar to, or better than, those in the warfarin treated group. These doses of edoxaban are being compared with warfarin in the ongoing ENGAGE AF-TIMI 48 trial.
- Edoxaban demonstrated significant dose-dependent reductions in venous thromboembolism after total knee or hip replacement surgery.
These data are encouraging for patients and support edoxaban’s potential to significantly streamline anticoagulation management, while providing effective protection against severe thromboembolic events like stroke. Results from the phase II studies are important because they have been used to establish the optimal dosing regimen to pursue in the phase III clinical trial ENGAGE AF-TIMI 48.
Experts are anticipating the outcome of this phase III study.
“This study is intended to show that atrial fibrillation patients can be treated simply, effectively and safely with once-daily administration of the factor Xa inhibitor edoxaban,” said Robert Giugliano, senior investigator, TIMI-Study Group, associate physician and assistant professor in medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, US.
ENGAGE AF-TIMI 48 compares two different doses of edoxaban with warfarin in patients with AF. Approximately 16,500 patients will be enrolled in this double-blind trial from 1,400 clinical sites worldwide.
Patients will be assigned, in a double-blind, double-dummy fashion, to one of three treatment groups: 30mg edoxaban once daily, 60mg edoxaban once daily or warfarin. Edoxaban will be given in fixed doses without coagulation monitoring. In contrast, the dose of warfarin will be adjusted to maintain the international normalised ratio (INR) between 2.0 and 3.0. The primary efficacy endpoint is stroke and systemic events, while the primary safety endpoint is the occurrence of major and clinically relevant non-major bleeding events, using the sensitive ISTH (International Society on Thrombosis and Haemostasis) scale. The expected median treatment duration in the study is 24 months; the sponsor, Daiichi Sankyo, expects the study to conclude in the first half of 2012.