The FINANCIAL — Daiichi Sankyo Company, Limited announced that its investigational once-daily oral, direct factor Xa inhibitor, edoxaban, was shown to be superior to enoxaparin in preventing venous thromboembolic (VTE) events in patients following total knee replacement (TKR), a type of major orthopedic surgery.
Results from the Phase III STARS E-3 (Studying Thrombosis After Replacement Surgery) study were presented at the 21st International Congress on Thrombosis (ICT) in Milan, Italy.(i)
This multicenter, double-blind, double dummy, centrally randomized trial evaluated the efficacy and safety of edoxaban compared with enoxaparin in patients undergoing TKR in Japan and Taiwan. A total of 716 patients received either 30 mg once-daily oral dose of edoxaban or subcutaneous injection of enoxaparin 2,000 international units (equivalent to 20 mg) twice-daily for 11 to 14 days. The primary efficacy endpoint of the trial was the incidence of symptomatic pulmonary embolism (PE) and symptomatic and asymptomatic deep vein thrombosis (DVT). The primary safety endpoint was the incidence of major bleeding and clinically relevant non-major bleeding.
DVT occurred in 7.4 percent of patients receiving edoxaban once-daily compared with 13.9 percent of patients who received enoxaparin (relative risk reduction of 46.8 percent; p=0.01). There were no PE events observed in either treatment group. There was no statistically significant difference in major and clinically relevant non-major bleeding (p=0.13). There were no cases of intracranial hemorrhage or death in either treatment group.
Indicators for potential liver damage in both treatment groups were carefully monitored during this trial by measuring bilirubin and serum aminotransferase levels.(ii) Elevations greater than three times the upper limit of the normal range of serum aminotransferase levels occurred in 1.4 percent of patients taking edoxaban compared with 8.0 percent of those taking enoxaparin.
“The combination of efficacy, tolerability and convenient once-daily oral dosing in this clinical setting further supports the potential role of edoxaban in helping patients and physicians avoiding thrombotic events,” said Dr. Takeshi Fuji, Head of Orthopedic Surgery, Osaka Koseinenkin Hospital. “These results are encouraging as they demonstrate superior efficacy of once-daily edoxaban compared with twice daily subcutaneous enoxaparin, the current standard of care for this patient population.”
In March 2010, Daiichi Sankyo submitted a New Drug Application to the Ministry of Health, Labor and Welfare in Japan seeking approval of edoxaban for the prevention of VTE after major orthopedic surgery.