FDA Expands Eliquis Label to Include Treatment of Deep Vein Thrombosis and Pulmonary Embolism
Treatment superior to enoxaparin/warfarin in reducing major bleeding
The FDA has approved a supplemental new drug application (sNDA) for Eliquis (apixaban, Bristol-Myers Squibb/Pfizer) for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and for reducing the risk of recurrent DVT and PE after initial therapy.
Combined, DVT and PE are known as venous thromboembolism (VTE). It is estimated that, every year, approximately 900,000 Americans are affected by DVT and PE.
DVT is a blood clot in a vein, usually in the lower leg, thigh, or pelvis, that partially or totally blocks the flow of blood. PE is a blood clot blocking one or more vessels in the lungs. DVT causes multiple symptoms, including pain, swelling, and redness, and can progress to PE, which carries the risk of sudden death.
The full prescribing information for Eliquis includes boxed warnings for the increased risk of thrombotic events in patients who prematurely discontinue the drug; and for the increased risk of epidural or spinal hematoma, which may cause long-term or permanent paralysis, in patients using apixaban and undergoing spinal epidural anesthesia or spinal puncture.
Apixaban increases the risk of bleeding and can cause serious, potentially fatal, bleeding.
The FDA approval of Eliquis for the treatment of DVT and PE, and for the reduction in the risk of recurrent DVT and PE following initial therapy, is based on data from the global AMPLIFY and AMPLIFY-EXT studies.
The AMPLIFY study, a randomized, double-blind trial, was designed to demonstrate the efficacy and safety of apixaban for the treatment of DVT and PE, and included patients with confirmed symptomatic DVT or PE. A total of 2,609 patients received apixaban, and 2,635 patients received standard of care, which consisted of initial enoxaparin treatment for at least 5 days, overlapped by oral warfarin therapy (International Normalized Ratio range: 2.0–3.0) for 6 months.
In the AMPLIFY study, apixaban 10 mg twice daily for 1 week followed by 5 mg twice daily for 6 months demonstrated efficacy comparable with that of standard of care in treating patients with DVT and PE for the primary efficacy composite endpoint of recurrent, symptomatic VTE or VTE-related death (2.3% vs. 2.7%, respectively; relative risk [RR] = 0.84; P < 0.0001 for noninferiority).
Apixaban demonstrated superiority in the primary safety endpoint of major bleeding compared with standard of care (0.6% vs. 1.8%, respectively; RR = 0.31; P < 0.0001 for superiority). Major bleeding was defined as clinically overt bleeding that was accompanied by one or more of the following: a decrease in the hemoglobin level of 2 g/dL or more; a transfusion of two or more units of packed red blood cells; bleeding that occurred in at least one of the following critical sites: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, or retroperitoneal; or bleeding that was fatal.
For the secondary safety endpoint in the AMPLIFY study, the event rates for clinically relevant non-major bleeding (CRNM) were fewer in apixaban-treated patients compared with those given standard of care (3.9% vs. 8.0%, respectively). CRNM was defined as overt bleeding that did not meet the criteria for major bleeding but was associated with a medical intervention, contact with a physician, interruption of the study drug, or discomfort or impairment in carrying out daily activities.
In the AMPLIFY trial, the discontinuation rate due to bleeding events was 0.7% in the apixaban group compared with 1.7% in the enoxaparin/warfarin group.
Eliquis (apixaban) now has the following indications:
- To reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation
- For the prophylaxis of DVT, which may lead to PE, in patients who have undergone hip- or knee-replacement surgery
- To treat DVT and PE, and to reduce the risk of recurrent DVT and PE following initial therapy
Source: Pfizer; August 21, 2014.