Oral apixaban appeared efficacious in treating venous thromboembolism

Researchers conducting the Botticelli DVT study in the Netherlands and the United States concluded that apixaban, an Xa inhibitor being developed by Bristol-Myers Squibb and Pfizer, was ready to move into phase-3 testing following the results of a recent trial.

The results of a phase-2 dose-ranging study were published in a recent issue of the Journal of Thrombosis and Haemostasis.

Researchers randomly assigned 520 patients to 84 to 91 days of 5 mg apixaban twice-daily, 10 mg twice-daily or 20 mg once-daily, or low-molecular weight heparin followed by a vitamin K antagonist.

They determined whether patients achieved the primary outcome of symptomatic recurrent venous thromboembolism and asymptomatic deterioration of bilateral compression ultrasound or perfusion lung scan; and the principal safety outcome of a composite of major and clinically relevant, non-major bleeding.

Researchers found that 17 of the 358 patients in the apixaban arm achieved the primary outcome (95% CI, 2.8%–7.5%), as did five of the 118 patients treated with heparin and the vitamin K antagonist (95% CI, 1.4%–9.6%).

Twenty-eight of the patients treated with apixaban achieved the principal safety outcome, as did 10 of 126 patients in the heparin arm. – by Jason Harris

J Thromb Haemost. 2008; 6:1313-1318.

Apixaban is an oral direct factor Xa inhibitor with high bioavailability, which is being developed without the need for laboratory monitoring. It is one of several promising new anticoagulants in advanced phases of clinical development. The drug appears to be effective at the two daily doses tested, but no dose response was observed with respect to efficacy or safety. Phase-2 studies of new anticoagulants in the treatment of symptomatic deep vein thrombosis characteristically have low event rates; the efficacy endpoints include asymtomatic deterioration of bilateral compression ultrasound or perfusion lung scan along with symptomatic recurrent venous thromboembolism. In phase-2 DVT treatment trials of other factor Xa inhibitors, a relatively flat dose response curve was also found. Thus, given the limited number of patients in each arm of the trial, such phase-2 trials just give you a sense of ‘being in the ballpark’ before going into a large phase-3 study, which will be powered for non-inferiority against standard therapy.

– Kenneth A. Bauer, MD

HemOnc Today Editorial Board member