Eliquis phase 3 study results

Results from the six month phase 3 AMPLIFY trial of 5,395 patients with acute venous thromboembolism (VTE), which included symptomatic deep vein thrombosis (DVT) and/or pulmonary embolism (PE), have recently been announced.

In this trial, apixaban as a single-agent achieved the primary efficacy endpoint of non-inferiority to conventional therapy (transition from initial parenteral enoxaparin to warfarin therapy) in the reduction of the composite endpoint of recurrent symptomatic VTE or VTE-related death.

Apixaban also met the primary safety endpoint of superiority for major bleeding, with a 69% relative risk reduction (RRR) compared to conventional therapy (absolute risk reduction [ARR] 1.2%; p<0.001 for superiority). Importantly, AMPLIFY demonstrated comparable results for the primary efficacy and safety endpoints between patients entering the study with a DVT or a PE. The findings were published online in the New England Journal of Medicine and presented at the 24th Congress of the International Society on Thrombosis and Haemostasis (ISTH).

Dr Alexander Cohen, Honorary Consultant Vascular Physician at King’s College Hospital said, “In the AMPLIFY trial apixaban was shown to be effective in the treatment of venous thromboembolism, with the additional benefit of having a significantly lower risk of bleeds compared to current standard therapies, which is positive news for patients and healthcare professionals. Subject to regulatory approval, this improved risk benefit profile will provide clinicians with confidence when considering prescribing this treatment and provide reassurance for patients. The fact it is an oral treatment has additional advantages in terms of convenience for patients and potential cost-savings for hospitals.”

Apixaban is not currently licensed for the treatment of venous thromboembolism. Based on the results of AMPLIFY, as well as AMPLIFY-EXT,3 which were published online on December 8, 2012, in New England Journal of Medicine with simultaneous presentation during a late-breaker session at the 54th Annual Meeting of the American Society of Hematology (ASH), Bristol-Myers Squibb and Pfizer plan to initiate regulatory filings for the initial and long-term treatment of VTE, as well as for extended prevention of recurrent VTE.

Venous thromboembolism, or VTE, is a spectrum of disease that encompasses two serious conditions: deep vein thrombosis (DVT), a blood clot in a deep vein, usually in the leg, that partially or totally blocks the flow of blood; and pulmonary embolism (PE), a blood clot in the pulmonary artery blocking one or more vessels in the lungs. VTE continues to be a major cause of morbidity and mortality, with more than one million VTE events estimated to occur annually across six major EU countries (UK, France, Germany, Italy, Spain and Sweden).

Once a VTE has occurred, up to 30% of people may have a VTE recurrence in the long term, some of which could potentially be fatal. About AMPLIFY AMPLIFY, (Apixaban for the initial Management of PuLmonary embolIsm and deep vein thrombosis as First-line therapY), a randomised, double-blind, multicentre trial, included 5,395 patients with confirmed symptomatic DVT or PE requiring treatment for six months, and evaluated apixaban as a single-agent (10mg twice daily for 7 days followed by 5mg twice daily thereafter) compared to conventional therapy (transition from initial parenteral enoxaparin to warfarin therapy). Approximately one third of patients in the trial had a PE at the time of enrolment into the study.

The primary efficacy outcome was the composite endpoint of recurrent symptomatic VTE or VTE-related death. (Recurrent VTE included fatal or non fatal PE and nonfatal DVT). For the primary efficacy outcome, apixaban achieved non-inferiority to conventional therapy in the reduction of recurrent symptomatic VTE or VTE-related death. The primary efficacy outcome occurred in 59 patients in the apixaban group (2.3%) and 71 patients (2.7%) receiving conventional therapy (relative risk 0.84; ARR 0.4%; 95% CI, 0.60 to 1.18; p<0.001 for non-inferiority).

Apixaban achieved the primary safety endpoint of superiority for major bleeding. Major bleeding occurred in 0.6% of patients given apixaban and 1.8% of those given conventional therapy (relative risk 0.31; ARR 1.2%; 95% CI, 0.17 to 0.55; p<0.001 for superiority). The composite of major and clinically relevant nonmajor bleeding occurred in 4.3% and 9.7% of patients in the apixaban and conventional-therapy groups, respectively (relative risk 0.44; ARR 5.4%, 95% CI, 0.36 to 0.55; p<0.001). Rates of other adverse events were similar in the two groups. AMPLIFY demonstrated comparable results for the primary efficacy and safety endpoints between patients entering the study with a DVT or a PE.