Portola To Seek Xarelto Reversal Agent Approval Before End of Year

Portola Pharmaceuticals indicates that it will likely ask federal regulators to approve a reversal agent for Xarelto before the end of the year, providing an antidote to stop the blood thinning effects and allow doctors to control bleeding problems on Xarelto.

Following recent clinical trials, the drug manufacturer says that it believes it has developed a safe and effective antidote for Xarelto, which has been linked to hundreds of adverse event reports involving uncontrollable bleeds and wrongful death.

The FDA must review and grant approval for the drug before the Xarleto reversal agent can be released on the market.

The findings of the phase III clinical trials were published in the online edition of the New England Journal of Medicine on November 11, and were also presented at the American Heart Association Scientific Sessions 2015 the same day, according to a Portola press release.

If approved, the reversal agent, andexanet alfa, would give doctors a way to quickly reverse the blood thinning effects of the new-generation oral anticoagulant sold by Bayer and Johnson & Johnson.

Xarelto (rivaroxaban) is part of a new class of blood thinners introduced in recent years as a replacement for warfarin. It is most commonly prescribed to reduce the risk of blood clots and strokes among patients with atrial fibrillation or following hip or knee replacement surgery. It was developed and is distributed jointly by Johnson & Johnson’s Janssen Pharmaceuticals subsidiary and Bayer Healthcare.

Known as a factor xa drug, Xarelto was designed to compete with Boehringer Ingelheim’s Pradaxa, which is another member of the same class of medications, which are designed to be easier to use than warfarin, since they do not require consistent monitoring to maintain appropriate dosage. A third member of this new class is Eliquis, and all three medications have been aggressively promoted in direct-to-consumer advertisements in recent years.

Problems with Xarelto, Pradaxa and Eliquis have been reported due to the lack of an antidote for any of the medications at the times they were released, often leaving doctors helpless to stop bleeds that may develop among users of the blood thinners. While users of warfarin can be given a dose of vitamin K to reduce the blood thinning effects of the medication, there were no similar reversal agents available for Pradaxa, Xarelto or Eliquis until recently.

Last month, the FDA approved the use of Praxbind, a reversal agent for Pradaxa. This has been seen by many observers as a clear market advantage for Pradaxa in this lucrative treatment field, increasing the pressure on the makers of Xarelto to finalize their own reversal agent.

According to Portola, the final stage of clinical trials for a Xarelto reversal agent involved 39 healthy volunteers ages 50 to 68 who were given Xarelto. The company claims that the trials indicated that andexanet alfa reduced the effects of Xarelto by 97% for one to two hours after it was administered.

Bleeding Lawsuits Over Xarelto, Pradaxa and Eliquis

The introduction of safe and effective reversal agents may signal the end to years years of mounting lawsuits against the drug makers, which have been brought on behalf of individuals who have suffered severe and often fatal bleeding problems.

More than 4,000 Pradaxa lawsuits have been filed by users of that drug who suffered bleeding injuries, alleging that Boehringer Ingelheim failed to adequately warn about the risk or disclose the lack of an effective reversal agent at the time the medication was introduced.

Following several years of litigation, Boehringer Ingelheim ultimately agreed to pay $650 million in Pradaxa settlements last year, with an average of about $150,000 per claim. However, the drug maker as continued to face new Pradaxa claims brought by individuals who have experienced emergency bleeding problems since the settlement.

Over the past year, there have been a mounting number of Xarelto lawsuits, raising nearly identical allegations. There are currently more than 2,800 product liability lawsuits pending against Bayer and Johnson & Johnson’s Janssen subsidiary over failure to adequately warn about the bleeding risks.

Since December 2014, the federal Xarelto cases have been consolidated as part of an MDL, or multidistrict litigation, with all cases centralized before U.S. District Judge Eldon Fallon in the Eastern District of Louisiana for coordinated handling during discovery and a series of early “bellwether” test trials, which are designed to help the parties gauge how juries may respond to certain evidence and testimony that is likely to be repeated throughout a large number of claims.

In recent months, there have also been a number of Eliquis lawsuits filed by individuals throughout the U.S., raising nearly identical allegations.