Pradaxa Antidote to be Tested on Emergency Room Bleeds

A potential antidote for Pradaxa will be tested on patients showing up at emergency rooms with bleeds, as concerns continue to mount about the risk of uncontrollable bleeding associated with the anticoagulant and with other drugs from the same new class, which includes the blockbuster medication Xarelto.

Boehringer Ingelheim has announced that it is in the final stages of testing idarucizumab, which the drug manufacturer says may work as a Pradaxa reversal agent, allowing doctors to quickly stop the blood thinning effects of the medication if users suffer a traumatic injury or if internal bleeding develops during use of the anticoagulant.

The potential Pradaxa antidote will be tested at more than 200 sites in 30 countries around the world as part of clinical trials being called Re-Verse Ad. It will be tested 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.

Uncontrollable Bleeding Problems with Pradaxa, Xarelto

Pradaxa (dabigatran) was introduced in late 2010, as the first member of a new generation of anticoagulants designed to replace Coumadin (warfarin) as the “go-to” medication for prevention of strokes due to atrial fibrillation.

Other members of this new class introduced after Pradaxa include Eliquis and Xarelto, which has grown to become the most widely used of this new generation of anticoagulants.

All of the medications have been promoted as superior alternatives to warfarin, because they are easier to use and do not require blood level monitoring during treatment. However, doctors are able to give a dose a vitamin K and fresh frozen plasma to users of warfarin who experience bleeding problems, quickly reversing the older drug’s blood thinning effects. No such reversal agents are currently available for Pradaxa, Xarelto or Eliquis.

During the first year Pradaxa was on the market, it quickly grew to become 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 thousands of 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 and sales have slowed in recent years.

Following several years of litigation, the drug maker agreed to pay $650 million in Pradaxa settlements earlier this year, with an average of about $150,000 to be awarded to former users who experienced injuries associated with uncontrollable bleeds.

Xarelto (rivaroxaban) was the second member of this new class of anticoagulants to be approved by the FDA, hitting the market about a year after Pradaxa. However, as Boehringer Ingelheim faced mounting lawsuits and publicity over severe bleeding events associated with Pradaxa, Xarelto quickly overtook the top spot among the new medications, with sales exceeding those of Pradaxa last year.

A growing number of Xarelto bleeding lawsuits are now being pursued on behalf of former users, raising similar allegations that inadequate warnings were provided about the lack of an approved reversal agent and claiming that the drug makers should have never introduced the medication without an antidote to allow doctors to reverse bleeding events.

To secure the position of dominance in this new class of anticoagulants, Boehringer Ingelheim and the makers of Xarelto, Bayer and Johnson & Johnson, have been each attempting to identify and secure approval for an effective reversal agent for their specific medication.

In June, the FDA granted “breakthrough status” to fast-track the approval process for Boehringer Ingelheim’s possible Pradaxa antidote, meaning that the drug has been placed at the front of the line for development and review in hopes of getting it to the market more rapidly.

Last year, Bayer and Johnson & Johnson indicated that they were working with a company called Portola Pharmaceuticals to develop an Xarelto reversal agent, but the drug makers are continuing to aggressively market their drug and push for expanded uses even without an approved antidote.