Eliquis Reversal Agent May Be Available Before Antidote for Xarelto or Pradaxa

As concerns continue about the risk of serious and potential life-threatening bleeding with Eliquis, Xarelto and Pradaxa, it appears that the makers of Eliquis may be close to introducing the first reversal agent for any of the drugs that are part of this new generation of anticoagulants. 

Pradaxa, Xarelto and Eliquis have all been introduced in recent years as a replacement for warfarin, which has been the go-to-drug for prevention of strokes due to atrial fibrillation for decades, and the manufacturers are all competing to gain the market advantage in this lucrative sector.

The new medications have been promoted as superior alternatives to warfarin, since the manufacturers indicate they require less monitoring than warfarin. However, the drugs have been linked to thousands of reports involving uncontrollable bleeding, which doctors have been unable to stop due to the lack of any reversal agents for the medications.

While all blood thinners carry a risk of bleeding events, warfarin has an effective antidote available, which doctors can use to quickly counteract the anticoagulant effects if bleeding problems develop among users.

The makers of Pradaxa, Xarelto and Eliquis have all been working to identify and obtain approval for a safe and effective reversal agent for their medication, which would likely provide the first to market with such an antidote a clear market advantage.

In a statement issued on October 1, Portola Pharmaceuticals indicated that a potential antidote for Eliquis has met both primary and secondary endpoints with high statistical significance in a phase 3 clinical trial, suggesting that they are close to confirming that tAndexanet Alfa can reliably stop the blood thinning effects of the drug in an emergency.

Bleeding Problems and Search for Antidote

Shortly after Boehringer Ingelheim introduced Pradaxa (dabigatran) as the first member of this new generation of drugs in October 2010, it became a “blockbuster” drug, generating over $1 billion in annual sales. However, it also quickly earned the dubious distinction as one of the medications most commonly associated with adverse event reports submitted to the FDA.

Amid reports involving users who suffered uncontrollable bleeding problems, Boehringer Ingelheim faced over 4,000 Pradaxa lawsuits alleging that inadequate warnings were provided about the lack of an available reversal agent for the medication, which the drug maker ultimately agreed to pay more than $650 million to settle.

Xarelto (rivaroxaban) was the second of this new generation to be approved by the market, introduced by Bayer and Johnson & Johnson in late 2011.

Amid concerns over the safety of Pradaxa, Xarelto quickly took over the top spot, with sales exceeding those of Pradaxa last year. However, there are now a growing number of Xarelto bleeding lawsuits being pursued on behalf of individuals nationwide, raising similar allegations that the drug makers never should have introduced the medication without an antidote to allow doctors to reverse bleeding events.

Eliquis (apixaban) was introduced by Pfizer and Bristol Myers-Squibb in 2012, as the third member of this new generation, and the drug makers have recently begun more aggressive marketing in hopes of toppling Xarelto. The drug makers have also obtained expanded approval for the anticoagulant, with the FDA approving use for the prevention and treatment of blood-clot related problems, such as deep vein thrombosis and pulmonary embolism.

Obtaining approval for an Eliquis reversal agent would give the drug a definitive edge among its competitors, potentially coming before antidotes being worked on by manufacturers of the other members of this new generation of drugs.

In February 2013, Bayer, Johnson & Johnson and Portola Pharmaceuticals announced that they planned to collaborate on the development of a Xarelto reveral agent, indicating that the companies will study the potential use of the recombinant protein PRT4445.

Earlier this year, the FDA granted “breakthrough status” to a potential Pradaxa antidote, idarucizumab, meaning that the drug would go to the front of the line for development and review in hopes of getting it to the market more rapidly.

The potential Pradaxa reversal agent is being tested at more than 200 sites in 30 countries around the world as part of clinical trials being called Re-Verse Ad, evaluating the effects of the antidote when used on patients taking Pradaxa who go to the emergency room due to uncontrollable bleeding and on users of the drug who require emergency surgery, where they are unable to stop the medication in advance of the procedure.

Detailed data on the use of andexanet alfa as a potential Eliquis antidote will be presented during a session at the American Heart Association’s 2014 Scientific Sessions, on Monday, November 17. The statement issued last week indicates that the reversal agent for Eliquis has the potential to be the first antidote approved for Factor Xa inhibitors, with the drug makers anticipating the filing of a Biologics License Application with the FDA for Accelerated Approval at the end of 2015.