Phase III EINSTEIN trial program: XARELTO reduces risk of DVT and PE

Janssen Pharmaceuticals, Inc.Sep 21 2013

Janssen Pharmaceuticals, Inc. (Janssen) announced today a newly published, pooled analysis of the Phase III EINSTEIN trial program, showing XARELTO^® (rivaroxaban) is as effective as the standard of care in reducing the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in people with symptomatic DVT or PE, while reducing the incidence of major bleeding by 46 percent. The analysis also found safety and efficacy outcomes for XARELTO^® were consistent across four subgroups of participants: fragile subjects, those with cancer, subjects with a history of a recurrent venous thromboembolism (VTE) and those presenting with a large clot. These findings were published in Volume 11, Issue 21 of the Thrombosis Journal.

DVT is a condition in which blood clots form in one of the large, deep veins, usually in the legs. PE is a serious condition that most commonly occurs when part or all of a DVT dislodges and travels to the lung, via the heart, where it can partially or completely block a branch of the pulmonary artery. When PE occurs with large clots, multiple clots, or when the patient already has pre-existing heart or lung disease, the event may be fatal. Each year up to 900,000 Americans experience a DVT or PE, resulting in up to 300,000 deaths. 

"The current standard of care for treatment of DVT and PE requires a two-drug regimen: a rapidly acting, injectable anticoagulant followed by long-term treatment with an oral Vitamin K antagonist, such as warfarin," said Jack E. Ansell, M.D., MACP, Professor of Medicine at New York University School of Medicine. "This analysis confirms an oral, single-drug option like XARELTO^® can simplify treatment and has a lower incidence of major bleeding compared to standard of care. It effectively reduces the risk of DVT and PE while eliminating the need for routine blood monitoring and frequent dose adjustments."   

This pre-specified pooled analysis included results from the EINSTEIN-DVT and EINSTEIN-PE studies. The analysis included more than 8,000 participants, split between the DVT (3,449) and PE (4,833) studies, indicating the XARELTO^® treatment benefit can be expected for subjects with either condition. Results from this pooled analysis were presented at the 54^th American Society of Hematology (ASH) Annual Meeting in Atlanta in December 2012.

XARELTO^® is the most-prescribed novel oral anticoagulant in the U.S. market today and is approved for six clinical uses in the U.S. It has earned the broadest reimbursement profile among novel anticoagulants, with 85 percent of patients on Medicare Part D and 85 percent of commercial patients covered at the lowest branded co-pay. To date, more than 5 million patients have received XARELTO^® worldwide and more than 3 million prescriptions have been written for XARELTO^® in the U.S.

The EINSTEIN-PE study was an open-label, randomized, non-inferiority trial. The trial compared oral rivaroxaban – 15 mg twice daily for three weeks, followed by 20 mg once daily – with the current standard of care (enoxaparin followed by a Vitamin K Antagonist [VKA]) in subjects with acute symptomatic PE with or without symptomatic DVT. Patients received treatment for six or 12 months. EINSTEIN-PE enrolled 4,833 participants and is the largest study ever conducted in the acute treatment of PE. Results from EINSTEIN-PE were presented at the American College of Cardiology Annual Scientific Sessions, and published in the New England Journal of Medicine in March 2012 (n engl j med 10.1056).

The EINSTEIN-DVT study compared the safety and efficacy of oral rivaroxaban –administered at 15 mg twice daily for three weeks followed by 20 mg once daily – with standard therapy. More than 3,400 participants with acute symptomatic DVT in the deep veins of the knee or thigh, but without any symptoms of PE, were enrolled and received treatment for three, six or 12 months. Results from EINSTEIN-DVT were presented at the annual European Society of Cardiology Congress in August 2010.

This pooled analysis of the EINSTEIN-DVT and -PE studies was pre-specified to be able to assess the overall efficacy and safety of XARELTO^® for the treatment of VTE.