Antidote Reverses Anticoagulation Activity of Rivaroxaban: ANNEXA-R

January 09, 2015

SAN FRANCISCO, CA — Portola Pharmaceuticals, the makers of an antidote for rivaroxaban (Xarelto, Bayer Pharma/Janssen Pharmaceuticals), a factor Xa inhibitor that is part of the newest generation of oral anticoagulants, announced today that a phase 3 study testing the safety and efficacy of the antidote met its primary end point[1].

In the trial, an 800-mg intravenous bolus of andexanet alfa, which was tested in 41 healthy volunteers treated with rivaroxaban 20 mg for 4 days and then subsequently randomized to the study drug or placebo, "immediately and significantly" reversed the steady-state anticoagulation activity of rivaroxaban.

The full results of the study, known as ANNEXA-R, are scheduled for presentation on Monday, March 16, 2015 at the American College of Cardiology 2015 Scientific Sessions in San Diego, CA, as part of an oral session highlighting original research. The antidote has already been shown to successfully reverse the anticoagulation activity of apixaban (Eliquis, Bristol-Myers Squibb/Pfizer).

In the second part of the ANNEXA-R study, investigators are testing the safety and effectiveness of andexanet alfa administered as an intravenous bolus followed by a continuous infusion of 8 mg/min for 120 minutes. These results are expected in the middle of 2015.

Andexanet alfa is currently being tested as an antidote to edoxaban (Savaysa, Daiichi Sankyo), the newest oral anticoagulant just approved by the US Food and Drug Administration, and the still-unavailable betrixaban (Portola Pharmaceuticals). Boehringer Ingelheim is in the process of developing an antidote specific to its own drug, dabigatran (Pradaxa), a direct thrombin inhibitor.

Currently, the FDA has designated andexanet alfa a breakthrough therapy, which is meant to help accelerate the development and review of drugs for serious or life-threatening conditions. This is awarded when early evidence suggests the agent represents a substantial improvement over existing therapies on one or more significant end points.

An antidote for the new generation of oral anticoagulants, of which none are yet available, would be welcomed by physicians for managing otherwise-uncontrolled bleeding. Bleeding related to warfarin can be reversed with low-dose vitamin K1 or a newer product, prothrombin complex concentrate (Kcentra, CSL Behring), but no such reversal agent exists for the factor Xa inhibitors or dabigatran.

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