AMPLIFY Trial Supports Eliquis for VTE Prevention

June 30, 2013—Bristol-Myers Squibb Company (Princeton, NJ) and Pfizer Inc. (New York, NY) announced the results of the 6-month, phase-3 AMPLIFY trial, which is evaluating the companies' Eliquis (apixaban), an oral factor Xa inhibitor administered in fixed doses for the treatment of acute venous thromboembolism (VTE). The findings were published by Giancarlo Agnelli, MD, et al online ahead of print in the New England Journal of Medicine and were announced at the 24th Congress of the International Society on Thrombosis and Hemostasis in Amsterdam, the Netherlands.

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, supported by the new results from AMPLIFY and the AMPLIFY-EXT trial data, which were presented in December 2012 at the 54th Annual Meeting of the American Society of Hematology and published by Dr. Agnelli, et al in the New England Journal of Medicine (2013;368:699–708).

Eliquis is currently approved to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation in the United States, the European Union, Japan, and a number of other countries around the world. It is also approved for VTE prevention in adult patients who have undergone elective hip or knee replacement surgery in the European Union and a number of other countries around the world. Eliquis is not approved for this indication in the United States, advised the company.

According to Bristol-Myers Squibb and Pfizer, this company-sponsored trial demonstrated that Eliquis, as a single-agent, achieved the primary efficacy endpoint of noninferiority to the current standard of care (initial parenteral enoxaparin treatment overlapped with warfarin therapy) in the reduction of the composite endpoint of recurrent symptomatic VTE or VTE-related death. Eliquis also met the primary safety endpoint of superiority for major bleeding, with a 69% relative risk (RR) reduction compared to the current standard of care. The companies noted that the trial demonstrated comparable results for the primary efficacy and safety endpoints between patients entering the study with deep vein thrombosis (DVT) or pulmonary embolism (PE).

AMPLIFY is a randomized, double-blind, multicenter trial. The study was composed of 5,395 patients with confirmed symptomatic DVT or PE requiring treatment for 6 months. The investigators evaluated Eliquis as a single agent (10 mg twice daily for 7 days followed by 5 mg twice daily thereafter) compared to the current standard of care (initial parenteral enoxaparin treatment overlapped by warfarin therapy). Approximately one-third of patients in the trial had a PE at the time of enrollment into the study.

As summarized by Bristol-Myers Squibb and Pfizer, Eliquis achieved noninferiority to parenteral enoxaparin plus warfarin for the primary efficacy outcome of the composite endpoint of recurrent symptomatic VTE (nonfatal DVT or nonfatal PE) or VTE-related death. The primary efficacy outcome occurred in 59 patients in the Eliquis group (2.3%) and in 71 patients (2.7%) receiving the current standard of care (RR. 0.84%; 95% confidence interval [CI], 0.6–1.18; P < .0001 for noninferiority).

Eliquis achieved the primary safety endpoint of superiority in major bleeding. Major bleeding occurred in 0.6% of patients who received Eliquis and 1.8% of those who received the current standard of care (RR, 0.31; 95% CI, 0.17–0.55; P < .0001 for superiority). The composite of major and clinically relevant nonmajor bleeding occurred in 4.3% and 9.7% of patients in the Eliquis and current standard of care groups, respectively (RR, 0.44; 95% CI, 0.36–0.55).

The rates of other adverse events were similar in the two groups. AMPLIFY demonstrated a comparable efficacy and safety profile between patients entering the study with a DVT and/or a PE. In patients enrolled with DVT, the primary efficacy outcome occurred in 38 patients (2.2%) in the apixaban group and 47 patients (2.7%) in the current standard of care group (RR, 0.83; 95% CI, 0.54–1.26; risk difference [apixaban minus current standard of care], -0.5%; 95% CI, -1.5–0.6). In patients enrolled with PE, the primary efficacy outcome occurred in 21 patients (2.3%) in the apixaban group and 23 patients (2.6%) in the current standard of care group (RR, 0.9; 95% CI, 0.5–1.61; risk difference, -0.3%; 95% CI, -1.7–1.2).

Dr. Agnelli, the study's lead investigator, commented on the AMPLIFY findings in the companies' press release. He stated, “The study results showed that apixaban, as a single agent, has comparable efficacy with significantly fewer major bleeding events, with respect to the standard of care. These results complement the previously published results for the AMPLIFY-EXT study. Together, these studies represent exciting data in the field of VTE treatment and indicate that apixaban may offer an important potential alternative in both acute and extended anticoagulation therapy for VTE patients.” Dr. Agnelli is Professor of Internal Medicine at the University of Perugia and Director of the Department of Internal and Cardiovascular Medicine and Stroke Unit at University Hospital in Perugia, Italy.