Xarelto Reversal Agent Study Proposed By Bayer, J&J, Portola

Bayer, Johnson & Johnson, and Portola Pharmaceuticals indicate that they are planning to collaborate on the development of an antidote for the blood thinner Xarelto, which would allow doctors to quickly reverse the anticoagulant effects of the medication and stop bleeding complications that may develop among users. 

The agreement was announced this week, indicating that the companies will study the potential use of the recombinant protein PRT4445 as a possible reversal agent for Xarelto side effects.

The antidote would be an important development, as recent research has suggested that between 1% and 4% of all patients receiving the medication experience uncontrolled bleeding, which can have serious and potentially life-threatening consequences.

Xarelto (rivaroxaban) is one of several new anticoagulants introduced in recent years as an alternative to Coumadin (warfarin), which are promoted as easier to take because they require less monitoring during treatment. It is part of a class of new blood thinners known as direct thrombin inhibitors.

The first medication approved from this class in the United States was Pradaxa (dabigatran), which was introduced in October 2010.  However, shortly after Pradadxa was introduced, a number of doctors began reporting severe complications where they were unable to stop bleeding that developed among users.

While warfarin has a reversal agent, vitamin K, which can be given to patients who experience hemorrhages or bleeding problems, Pradaxa and Xarelto currently have no such antidote or quick fix available.

The antidote study for Xarelto would be complete during the second half of this year, Bayer says, and will look at varying dosage strengths of PRT4445.

Pradaxa Bleeding Problems

After it became the first direct thrombin inhibitor introduced as a superior alternative to warfarin, Pradaxa quickly became widely used by doctors throughout the United States. However, it has also earned the dubious title of being one of the medications most commonly associated with adverse event reports submitted to the FDA.

According to a report by the Institute for Safe Medication Practices (ISMP), which analyzes all adverse event reports submitted by doctors and patients through the FDA MedWatch Program, there were at least 3,781 reports involving problems with Pradaxa during 2011, including 2,367 reports of hemorrhage and 542 deaths. This far eclipsed the 1,106 adverse event reports associated with warfarin, which was introduced in 1954 and has been a mainstay of anticoagulation treatment for decades.

Hundreds of individuals throughout the United States are now pursuing a Pradaxa lawsuit against Boehringer Ingelheim, alleging that the manufacturer of Pradaxa failed to adequately warn about the bleeding risk or the lack of a reversal agent.

Xarelto was introduced about a year after Pradaxa, for prevention of strokes among patients with atrial fibrillation. However, it generally has a much younger target population than Pradaxa, as it has also been approved by the FDA to prevent venous and pulmonary embolism in patients who are undergoing knee replacement surgery or hip replacement surgery.