New data presented on Phase 3 trial of ELIQUIS® (apixaban)
Posted: 13 November 2011 | | No comments yet
Bristol-Myers Squibb Company and Pfizer Inc. announced the results of the Phase 3 ADOPT trial…
Bristol-Myers Squibb Company (NYSE: BMY) and Pfizer Inc. (NYSE: PFE) today announced the results of the Phase 3 ADOPT (Apixaban Dosing to Optimize Protection from Thrombosis) trial, which evaluated apixaban versus enoxaparin in acutely ill medical patients, did not meet the primary efficacy outcome of superiority to enoxaparin for the endpoint of venous thromboembolism (VTE) and VTE-related death at day 30. The apixaban arm had a 13 percent lower rate of events than enoxaparin followed by placebo, which favored apixaban but was not statistically significant and thus no clinically directive conclusion can be drawn. The key safety outcome of major bleeding was low in both groups but occurred in more patients treated with apixaban than with enoxaparin (0.47 percent of patients in the apixaban group and 0.19 percent of patients in the enoxaparin group (P=0.04)). The study results were presented during a late-breaking session at the annual American Heart Association (AHA) Scientific Sessions in Orlando, FL, and published in the New England Journal of Medicine.
“Solving the problem of VTE post-hospitalization remains a critical unmet need in preventing medically ill patients from developing deep vein thrombosis and pulmonary embolism,” said Dr. Samuel Z. Goldhaber, senior cardiologist at Brigham and Women’s Hospital, and Professor of Medicine, Harvard Medical School, Boston, MA. “ADOPT provides important insights for clinical trialists designing studies of extended duration VTE prophylaxis among medically ill hospitalized patients.”
ELIQUIS ® (apixaban), a new oral direct Factor Xa inhibitor, is part of a class of agents being studied for their potential to prevent and treat blood clots in multiple indications. ELIQUIS is currently approved in the 27 countries of the European Union (EU) for the prevention of VTE in adult patients who have undergone elective total hip or knee replacement surgery.
ADOPT was a Phase 3, international, multicenter, randomized, double-blind, controlled study that compared apixaban to enoxaparin in acutely ill medical patients. Patients hospitalized with an expected stay of at least three days were randomly assigned to either oral apixaban (2.5 mg twice daily) for 30 days or to subcutaneous enoxaparin (40 mg once daily). Patients in the enoxaparin arm received treatment for a minimum of 6 days and a maximum of 14 days. Patients randomized to apixaban received daily injections of enoxaparin placebo for a minimum of 6 days and patients randomized to enoxaparin received apixaban placebo tablets for 30 days.
Of the 6,758 patients from 35 countries enrolled in the study, 6,528 patients were randomized for the analysis of the primary efficacy outcome defined as the composite of VTE-related death, fatal or non-fatal pulmonary embolism (PE), symptomatic or asymptomatic deep vein thrombosis (DVT) as detected by ultrasound and occurring within the 30-day intended treatment period. The statistical plan for the study required testing superiority of apixaban during the intended treatment period before testing for non-inferiority in the injectable treatment period.
When apixaban was compared to enoxaparin, the primary efficacy endpoint occurred in 2.71 percent of patients in the apixaban group and 3.06 percent of patients in the enoxaparin group, demonstrating a non-significant relative risk reduction for apixaban of 13 percent that was not superior to a shorter course of enoxaparin (P=0.44).
In ADOPT, the rate of dropouts was higher than expected across both treatment arms, including loss of patients to ultrasound examinations, and a lower than expected overall event rate, both of which contributed to the study being underpowered.
The key safety outcome of major bleeding was low in both groups but occurred in more patients treated with apixaban for 30 days than with enoxaparin for a minimum of six days and a maximum of 14 days. At Day 30, major bleeding occurred in 0.47 percent of patients in the apixaban group and 0.19 percent of patients in the enoxaparin group (P=0.04). Major and clinically relevant non-major bleeding occurred in 2.67 percent of patients who received apixaban and in 2.08 percent of patients who received enoxaparin (P=0.12).
Other measures of overall safety were similar for apixaban and enoxaparin in ADOPT. Among the safety endpoints of adverse events, serious adverse events, deaths, discontinuation due to AEs, and liver function test (LFT) elevations; apixaban appeared to be similar to enoxaparin.
About Venous Thromboembolism
Venous thromboembolism encompasses two serious conditions: deep vein thrombosis, a blood clot in a vein, usually in the leg that partially or totally blocks the flow of blood; and pulmonary embolism, a blood clot blocking a vessel in the lungs. Deep vein thrombosis causes multiple symptoms including pain, swelling and redness and, more importantly, can progress to pulmonary embolism, which carries the risk of sudden death.
ELIQUIS is the approved trade name for apixaban in Europe and the proposed trade name in the U.S. The companies recently announced the regulatory application for stroke prevention in atrial fibrillation was validated for review by the European Medicines Agency. The alliance expects to have an accepted filing in the U.S. for this indication by the end of 2011.
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 ADOPT. ELIQUIS is currently being evaluated in ongoing trials for the treatment of recurrent VTE, in the Phase 3 AMPLIFY and AMPLIFY-EXT trials.