The European Commission has approved Eliquis in the 27 countries of the European Union (EU) for the prevention of venous thromboembolic events (VTE) in adult patients who have undergone elective hip or knee replacement surgery. This decision marks the first approval for Eliquis, a new oral direct Factor Xa inhibitor being developed by the alliance of Bristol-Myers Squibb Company and Pfizer Inc.

“Major orthopedic surgery, such as total knee replacement or total hip replacement, puts patients at a very high risk of developing VTE or pulmonary embolism. The absolute risk of deep vein thrombosis for these patients ranges from 40 to 60 per cent when these patients do not receive preventive care,” said Michael Rud Lassen, M.D., Glostrup Hospital in Copenhagen, Denmark, and lead investigator for the phase 3 orthopaedic trials for Eliquis. “The approval of Eliquis gives European orthopaedic surgeons a new option in VTE prevention that is more effective than the current standard of care, enoxaparin 40 mg once daily, and importantly, without increasing bleeding.”

The approval of Eliquis is based on the ADVANCE-2 and ADVANCE-3 clinical trials, part of the EXPANSE clinical trial programme. In these trials, Eliquis given orally twice daily demonstrated superior efficacy versus enoxaparin 40 mg given once daily by injection in the prevention of VTE in total knee and total hip replacement, and did not increase the risk of bleeding versus enoxaparin. These trials randomized over 8,000 patients and assessed the safety and efficacy of Eliquis compared to enoxaparin. The primary efficacy endpoint of ADVANCE-2 and ADVANCE-3, which studied patients undergoing elective total knee or hip replacement, respectively, was defined as the composite of asymptomatic and symptomatic deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE), and death from any cause during study treatment. The principal safety measure in the trials was the composite of major and clinically relevant non-major bleeding.

Eliquis is the only oral anticoagulant with a 12- to 24-hour post surgery initiation window, which may help physicians to observe and stabilize post-surgical patients before beginning treatment. Eliquis is dosed 2.5 mg twice daily, requires no routine platelet or liver monitoring, and requires no dose adjustment in indicated patients. In patients undergoing hip replacement surgery, the recommended duration of treatment is 32 to 38 days. In patients undergoing knee replacement surgery, the recommended duration of treatment is 10 to 14 days.

“As the first Eliquis approval worldwide, today marks an important milestone for the Bristol-Myers Squibb/Pfizer Alliance,” said Beatrice Cazala, senior vice president, Commercial Operations, and president, Global Commercialization, Europe and Emerging Markets, Bristol-Myers Squibb. “We are confident that our shared resources and leadership in the treatment of cardiovascular disease will help make the European launch a success and continue to bring value to the development of Eliquis.”

“The approval of Eliquis provides a new oral option for patients in the EU undergoing elective hip or knee replacement surgery, where the risk of bleeding is a significant concern,” said Olivier Brandicourt, president and general manager, Primary Care, Pfizer Inc. “We are excited to bring this new agent to market in Europe and provide orthopaedic surgeons with an option that will help them to prevent VTE in patients undergoing elective total knee or total hip replacement surgery.”

VTE encompasses two serious conditions: DVT, a blood clot in a vein, usually in the leg that partially or totally blocks the flow of blood; and PE, a blood clot blocking one or more vessels in the lungs. DVT causes multiple symptoms including pain, swelling and redness and, more importantly, can progress to PE, which carries the risk of sudden death.

Eliquis is being investigated within the EXPANSE Clinical Trials Program, which is projected to include nearly 60,000 patients worldwide across multiple indications and patient populations and includes a total of nine completed or ongoing, randomized, double-blind Phase 3 trials, including the ADVANCE trials.

In addition to prevention of VTE in orthopaedic surgery, Eliquis is being investigated in phase 3 trials for the treatment of VTE, the prevention of VTE in hospitalized acutely ill medical patients and the prevention of stroke and other thromboembolic events in patients with atrial fibrillation.

In 2007, Pfizer and Bristol-Myers Squibb entered into a worldwide collaboration to develop and commercialize Eliquis, an investigational oral anticoagulant discovered by Bristol-Myers Squibb. This global alliance combines Bristol-Myers Squibb's long-standing strengths in cardiovascular drug development and commercialization with Pfizer’s global scale and expertise in this field.