J&JPRD announces rivaroxaban Phase 3 trial results against venous thromboembolism

Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD), today announced results from the MAGELLAN Phase 3 trial evaluating the investigational oral anticoagulant rivaroxaban for the prevention of venous thromboembolism (VTE) in hospitalized patients with acute medical illnesses.

In the study, rivaroxaban met its primary clinical efficacy objectives of demonstrating non-inferiority to enoxaparin in short-term use (10 ± 4 days), and superiority in long-term use (35 ± 4 days) when compared to short-term use of enoxaparin followed by placebo. The combined rates of major and clinically relevant non-major bleeding, the primary safety measure in the study, while low overall, were significantly higher in those treated with rivaroxaban compared with those treated with enoxaparin, followed by placebo. The results were presented today as a late-breaker at the American College of Cardiology Annual Scientific Session in New Orleans.

"MAGELLAN investigated the largest and most diverse population of hospitalized, acutely ill patients to date, and managing the risk of blood clots in these patients is extremely complex due to their age, co-morbid conditions and duration of immobilization," said Dr. Alexander T. Cohen, Honorary Consultant Vascular Physician in the Department of Surgery and Vascular Medicine at King's College Hospital, London and principal investigator of the study. "As observed in previous studies in this area, there is an ongoing risk of venous thrombosis and likewise a consistently positive benefit-risk balance was not seen across the heterogeneous, acutely ill patient population studied. Further analysis is required to identify which groups of patients in MAGELLAN may derive benefit from thromboprophylaxis with rivaroxaban."

Medically ill is a broad term used to classify a host of hospitalized patients that are typically immobilized during their hospital stay for treatment of a variety of reasons that can include heart failure, active cancer, acute ischemic stroke, acute infections, inflammatory diseases including acute rheumatic diseases, and acute respiratory insufficiency. Immobilization is a major risk factor for developing a VTE (an unwanted blood clot), and patients hospitalized due to medical illness are at high risk for VTE as they often have multiple risk factors which are generally cumulative.

In MAGELLAN, results for the primary endpoints in the study were:

• In the short-term (10 ± 4 days) evaluation, rivaroxaban achieved non-inferiority compared to enoxaparin (2.7% vs. 2.7%)
• In the long-term (35 ± 4 days), rivaroxaban was superior to short-term enoxaparin followed by placebo, demonstrating a 22.9% relative risk reduction (RRR) in the modified intent-to-treat (MITT) population (4.4% vs. 5.7%, respectively) This analysis included patients who received at least one dose study medication and had an adequate assessment of VTE.

For the primary safety measure - incidence of treatment-emergent major bleeding events and non-major, clinically relevant bleeding events observed no later than two days after the last intake of the double-blind study drug - there was a statistically significant increase at day 10 in patients randomized to the rivaroxaban arm compared with the enoxaparin arm (2.8% v. 1.2%, respectively, p<0.0001). At day 35, the primary safety event rate was 4.1% for rivaroxaban-treated patients compared with 1.7% for patients receiving enoxaparin followed by placebo (p<0.0001). Rates of other adverse events - including liver and cardiovascular - were similar across both study arms and rates for rivaroxaban were consistent with previous clinical trial data.

"The study confirms there is a continued risk of VTE beyond the period of hospitalization or immobilization, and that rivaroxaban reduces this risk," said Peter M. DiBattiste, M.D., Vice President of Cardiovascular Development at J&JPRD. "As with all anticoagulants, the benefits need to be evaluated in light of the bleeding results, and we are conducting additional analyses to help us better understand which patients in this population may benefit most from treatment with rivaroxaban."