The FDA ( Food and Drug Administration ) has approved a Supplemental New Drug Application ( sNDA ) for Eliquis ( Apixaban ) for the treatment of deep vein thrombosis ( DVT ) and pulmonary embolism ( PE ), and for the reduction in the risk of recurrent DVT and PE following initial therapy.
Combined, deep vein thrombosis and pulmonary embolism are known as venous thromboembolism. It is estimated that every year, approximately 900,000 Americans are affected by deep vein thrombosis and PE.
Once a VTE has occurred, approximately 33% of patients are at risk of a recurrence within 10 years.
The full Prescribing Information for Eliquis includes Boxed Warnings for the increased risk of thrombotic events in patients who prematurely discontinue Eliquis; and for the increased risk of epidural or spinal hematoma, which may cause long-term or permanent paralysis, in patients using Eliquis and undergoing spinal epidural anesthesia or spinal puncture.
Eliquis increases the risk of bleeding and can cause serious, potentially fatal, bleeding.
The FDA approval of Eliquis for the treatment of deep vein thrombosis and pulmonary embolism, and for the reduction in the risk of recurrent deep vein thrombosis 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 deep vein thrombosis or PE ( 2,609 for Apixaban and 2,635 for standard of care, which was initial Enoxaparin treatment for at least five days, overlapped by Warfarin therapy [ International Normalized Ratio ( INR ) range 2.0-3.0 ] orally for six months ).
In the AMPLIFY study, Apixaban 10 mg twice daily for one week followed by 5 mg twice daily for six months demonstrated efficacy comparable to standard of care in treating deep vein thrombosis and pulmonary embolism patients for the primary efficacy composite endpoint of recurrent, symptomatic venous thromboembolism, or venous thromboembolism-related death ( 2.3% vs. 2.7%, relative risk, 0.84; 95% confidence interval [CI], 0.60 to 1.18; P-value less than 0.0001 for noninferiority ).
Apixaban demonstrated superiority in the primary safety endpoint of major bleeding versus standard of care ( 0.6% vs. 1.8%, relative risk 0.31; 95% CI, 0.17 to 0.55; P less than 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, retroperitoneal; or bleeding that was fatal.
For the secondary safety endpoint in the AMPLIFY study, the event rates for clinically relevant nonmajor bleeding ( CRNM ) were fewer in Apixaban-treated patients compared to standard of care-treated patients ( 3.9% vs. 8.0% ).
Clinically relevant nonmajor bleeding 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 AMPLIFY, the discontinuation rate due to bleeding events was 0.7% in the Apixaban-treated patients compared to 1.7% in Enoxaparin / Warfarin-treated patients.
Apixaban is an oral selective Factor Xa inhibitor. By inhibiting Factor Xa, a key blood-clotting protein, Apixaban decreases thrombin generation and blood clot formation. ( Xagena )
Source: BMS & Pfizer, 2014