November 21,2013 | By Márcio Barra
Daiichi Sankyo’s edoxaban proved as effective and safer than warfarin in a Phase III trial of patients with atrial fibrillation, according to the results presented at the American Heart Association Scientific Sessions yesterday and published simultaneously online in The New England Journal of Medicine.
The trial, entitled ENGAGE AF-TIMI 48, compared two daily dosages of Edoxaban, 60 mg and 30 mg, against warfarin, dose-adjusted to achieve an international normalized ratio (INR) of 2.0 to 3.0, in the largest – 21,105 patients across 46 countries – and longest – 2.8 years average follow-up – clinical trial in the company’s history.
The study’s primary efficacy outcome – the annualized rate of stroke occurrence or systemic embolic event – was 1.18% among patients receiving 60 mg of edoxaban group versus 1.5% in the warfarin group and 1.61% in the edoxaban 30 mg arm, representing a 21% risk reduction. As for the primary safety endpoint – annualized rate of major bleeding occurence – it was 3.43% with warfarin, compared to 2.75% for edoxaban 60 mg and to 1.61% for edoxaban 30 mg. Moreover, the risk of hemorrhagic stroke went down 46% for edoxaban 60 mg and 53% for edoxaban 30 mg compared with warfarin, with less cardiovascular deaths occurring in patients treated with edoxaban compared to warfarin: 60 mg edoxaban 2.74% per year compared to warfarin 3.17% per year.
The trial did fail in proving that edoxaban was better than warfarin in the prevention of ischemic stroke. The rate of ischemic stroke was 1.25% with warfarin as compared with 1.25% with 60 mg edoxaban and 1.77% with 30 mg edoxaban
Edoxaban is a once-daily oral factor Xa inhibitor that, if approved (the drug is already approved in Japan for venous thromboembolism under the name Lixiana), will enter a highly competitive market. In the last 5 years, new oral anticoagulants, with either direct inhibition of factors IIa (thrombin) or Xa, were granted European and USA marketing authorization for the prevention of thrombotic events in high-risk adult patients. These include two factor Xa inhibitors, Bayer/Johnson & Johnson’s Xarelto (rivaroxaban) and Pfizer/Bristol-Myers Squibb’s Eliquis (apixaban) and Boehringer Ingelheim’s oral direct thrombin inhibitor Pradaxa (dabigatran etexilate). Warfarin is the current oral blood thinner standard, a status that the drug enjoys for over five decades.
Daiichi Sankyo is expected to file a marketing authorization request for Edoxaban by the first quarter of 2014.