Study shows that PCCs can reverse blood thinning effects of XARELTO in healthy subjects

Janssen Research & Development, LLC (Janssen) announced today results of an open label, single-center, parallel group study showing that a type of medication called prothrombin complex concentrates (PCCs) can reverse the blood thinning effects of XARELTO^® (rivaroxaban) in healthy subjects.

"PCCs can be used to reverse the blood thinning effects of anticoagulants such as warfarin and are important in emergency situations involving uncontrolled bleeding," said Dr. Marcel Levi, Professor of Medicine and Dean of Medicine at the Academic Medical Center of the University of Amsterdam. "These data provide additional information on how to potentially reverse the anticoagulant effects of XARELTO^®."

The study, presented today as an oral session at the International Society on Thrombosis and Haemostasis Annual Meeting in the Netherlands, evaluated three- and four-factor PCCs in 34 healthy adults treated with 20 mg of XARELTO^®. Participants were treated with XARELTO^® twice a day for four days. On the fifth day, participants received either a 50 IU/kg single bolus dose – quickly administered intravenously – of three-factor PCC (Profilnine SD), a four-factor PCC (Beriplex P/N), or a 100 mL single bolus dose of saline as a control.

Both three- and four-factor PCCs were found to partially reverse the XARELTO^®-induced prolongation of the prothrombin time (PT) – the time it takes the blood to clot – in healthy subjects, with the latter reducing the mean PT by 2.5 to 3.5 seconds (versus a 0.6 to 1.0 second reduction associated with three-factor PCC). Conversely, three-factor PCC had a greater effect on the reversal of XARELTO^®-induced changes in endogenous thrombin potential (ETP) – the total amount of thrombin generated during the test – than four-factor PCC.

There is currently no approved reversal agent for XARELTO^®. In February 2013, Janssen announced a clinical collaboration agreement with Portola Pharmaceuticals, Inc. and Bayer HealthCare to evaluate the safety of PRT4445 — an investigational-stage antidote for Factor Xa inhibitors — in healthy volunteers who have been administered XARELTO^®. The study is evaluating several dosage strengths of PRT4445 and its potential ability to reverse the anticoagulant activity of XARELTO^® in emergency situations.

"XARELTO^® is effective across multiple clinical uses in the U.S. and we are making inroads on ways the drug can be rapidly reversed when the need arises," said Troy Sarich, Vice President, Compound Development Team Leader at Janssen. "Our research into additional reversal strategies is helping to transform the science into medical solutions for the people who need them."

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 strongest 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 2 million prescriptions have been written for XARELTO^® in the U.S.