European Commission approves apixaban for treatment and prevention of recurrent DVT and PENews - Aug. 5, 2014
The European Commission has approved apixaban for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) and for the prevention of recurrent DVT and PE in adults. The approval applies to all European Union (EU) member states, as well as Iceland and Norway.
Apixaban, an oral selective Factor Xa inhibitor, had already received approval for the prevention of venous thromboembolism (VTE) in adults who have undergone elective total hip or knee replacement surgery, and for the prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation (NVAF) with one or more risk factors.
The marketing authorisation for apixaban follows the positive opinion issued by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency, and is supported by two pivotal Phase 3 clinical trials, AMPLIFY and AMPLIFY-EXT.
In AMPLIFY, apixaban (10 mg twice daily for seven days, followed by 5 mg twice daily for 6 months) was shown to be non-inferior to enoxaparin/warfarin in the combined primary endpoint of adjudicated recurrent symptomatic VTE (nonfatal DVT or nonfatal PE) or VTE-related death. Its efficacy in initial treatment of VTE was consistent between patients who were treated for a PE (RR: 0.9; 95%CI: 0.5- 1.6) or DVT (RR: 0.8; 95%CI: 0.5- 1.3). Efficacy across subgroups, including age, gender, body mass index (BMI), renal function, extent of index PE, location of DVT thrombus, and prior parenteral heparin use was generally consistent. Apixaban was statistically superior to enoxaparin/warfarin in the primary safety endpoint, major bleeding (RR: 0.31, 95 %CI: 0.17-0.55, P <0.0001).
The AMPLIFY-EXT study showed that both tested doses of apixaban (2.5 mg or 5 mg twice daily, or placebo, for 12 months after completing six to 12 months of initial anticoagulant treatment) were statistically superior to placebo in the primary endpoint of symptomatic, recurrent VTE (nonfatal DVT or nonfatal PE) or all-cause death. The efficacy for prevention of a recurrence of a VTE was maintained across subgroups, including age, gender, BMI, and renal function. The incidence in major bleeding during the treatment period for both doses was not statistically different from placebo.
The recommended dose of apixaban for the prevention of recurrent DVT and PE is 2.5 mg taken orally twice daily.