Credit: Kevin MacKenzie
The European Commission has approved apixaban (Eliquis) to treat and prevent deep vein thrombosis (DVT) and pulmonary embolism (PE).
The approval applies to all European Union (EU) member states, as well as Iceland and Norway.
Apixaban was already approved in the EU to prevent venous thromboembolism (VTE) in adults who have undergone total hip or knee replacement surgery, and to prevent stroke and systemic embolism in adults with nonvalvular atrial fibrillation.
The new marketing authorization for apixaban follows the positive opinion issued by the European Medicines Agency’s Committee for Medicinal Products for Human Use in June and is supported by results of 2 phase 3 clinical trials, AMPLIFY and AMPLIFY-EXT.
Results of AMPLIFY
The AMPLIFY trial included 5395 patients with confirmed, symptomatic DVT or PE requiring treatment for 6 months. They had a mean age of 56.9 years, and 89.8% of randomized patients had unprovoked VTE.
About half of patients (n=2691) were randomized to receive apixaban at 10 mg twice daily for 7 days, followed by 5 mg twice daily for 6 months.
The other half (n=2704) were randomized to the standard of care, which was enoxaparin at 1 mg/kg twice daily for at least 5 days until INR ≥ 2 and warfarin (target INR range 2.0-3.0) for 6 months.
Apixaban proved noninferior to standard therapy in the combined primary endpoint of adjudicated recurrent symptomatic VTE (nonfatal DVT or PE) or VTE-related death.
This outcome occurred in 2.3% of patients in the apixaban arm and 2.7% of patients in the standard-therapy arm (P<0.0001 for noninferiority).
Apixaban also proved superior to standard therapy with regard to bleeding. The composite endpoint of major bleeding and clinically relevant, nonmajor bleeding occurred in 4.3% of patients in the apixaban arm and 9.7% of patients in the standard-therapy arm (P<0.001).
Results of AMPLIFY-EXT
The AMPLIFY-EXT trial included 2486 patients who had completed 6 to 12 months of anticoagulation treatment for DVT or PE. The mean age was 56.7 years, and 91.7% of randomized patients had unprovoked VTE.
Patients were randomized to receive apixaban at 2.5 mg (n=842), apixaban at 5 mg (n=815), or placebo (n=829).
Both apixaban doses were significantly superior to placebo (P<0.001) with regard to the primary efficacy endpoint, which was recurrent VTE or all-cause death.
During the 12-month active study period, these events occurred in 3.8% of patients in the 2.5-mg arm, 4.2% of patients in the 5-mg arm, and 11.6% of patients in the placebo arm.
The primary safety endpoint was the incidence of major bleeding, and there was no significant difference among the treatment arms. Major bleeding occurred in 0.2% of patients in the 2.5-mg arm, 0.1% of patients in the 5-mg arm, and 0.5% of patients in the placebo arm.
About apixaban
Apixaban is approved to reduce the risk of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation in the US, EU, Japan, and a number of other countries around the world.
The drug is approved to prevent VTE in adult patients who have undergone elective hip or knee replacement surgery in the US, EU, and a number of other countries.
And now, apixaban is approved for the treatment of DVT/PE and the prevention of recurrent DVT/PE in the EU. The drug is not approved for this indication in the US.
Apixaban is under joint development by Pfizer and Bristol-Myers Squibb.
