Pradaxa Reversal Agent Gets Expedited FDA Review Process

Federal drug regulators have agreed to a fast-track review process for a potential reversal agent for the blood thinner Pradaxa, which has been linked to thousands of serious and sometimes fatal injuries due to uncontrollable bleeding events. 

Boehringer Ingelheim, the makers of Pradaxa, announced on April 23 that the FDA has granted Priority Review to an application for a drug called idarucizumab, which may be able to rapidly stop the blood thinning effects of the anticoagulant. The decision means that the drug’s review will be accelerated and, if approved, could get to patients faster than normal for new drugs.

If approved, idarucizumab would be the first reversal agent to hit the market for a new generation of oral anticoagulants used to prevent strokes in patients with atrial fibrillation. The class, which includes the blockbuster drugs Pradaxa, Xarelto, and Eliquis, has been linked to uncontrollable bleeding events because they were released without antidotes that doctors can use in the event patients suffer hemorrhages or other bleeding events.

The drugs have been promoted as superior replacements for warfarin, indicating that they are easier to use and require less frequent blood monitoring. However, unlike warfarin, which can be quickly reversed with a dose of vitamin K and fresh frozen plasma, there are no approved reversal agents for the medications.

“The FDA’s decision to grant Priority Review to the idarucizumab application is an important milestone and a step toward bringing a new innovative option in anticoagulation care to physicians and patients,” said Sabine Luik, MD, senior vice president, Medicine & Regulatory Affairs, Boehringer Ingelheim Pharmaceuticals, Inc, in the press release. “If approved, idarucizumab has the potential to be a significant evolution in care by providing physicians with an option for PRADAXA patients in rare emergency situations that may require rapid reversal of the anticoagulation effect of dabigatran.”

The FDA grants a Priority Review in cases where a drug can significantly improve the safety or effectiveness of a treatment of serious conditions. The agency gave the drug “breakthrough status” in June 2014 while the drug was going through initial testing.

The announcement comes just days after Portola Pharmaceuticals announced that testing indicated that its own reversal agent, andexanet alfa, had shown to be effective in reversing the blood thinning effects of both Eliquis and Xarelto. The manufacturer said the phase 3 trials had met both primary and secondary endpoint goals. It has also been granted breakthrough status for development.

Race For A Reversal Agent

As the popularity of the new generation of drugs has increased, concerns have emerged about the bleeding risk of Xarelto, Pradaxa and Eliquis.

Pradaxa (dabigatran) was the first member of this class to hit the market, introduced by Boehringer Ingelheim in October 2010. As the medication rose in popularity, more than 4,000 Pradaxa lawsuits were filed on behalf of former users who alleged that inadequate warnings about the lack of a reversal agent were provided for consumers and the medical community. Following several years of litigation, a Pradaxa settlement agreement was announced last year, with Boehringer Ingelheim agreeing to pay $650 million to resolve the claims for an average of about $150,000 each.

Xarelto (rivaroxoaban) was introduced in 2011, as the second member of this class, and it has since grown to become the best seller of the two. Bayer and Johnson & Johnson now face a growing number of Xarelto lawsuits, which raise nearly identical allegations from former users who suffered severe bleeding problems.

Eliquis (apixaban) was approved by the FDA in early 2013, and Bristol-Myers Squibb has aggressively marketed the medication in direct-to-consumer advertisements to increase use, even though it also lacks a currently approved reversal agent. To date, Elquis has not been targeted by a large number of complaints or lawsuits, but that may change as its popularity increases.

The FDA also recently announced the approval of a fourth member of this class, Savaysa (edoxaban), which will be marketed by Daiichi Sankyo.

The first manufacturer to get a reversal agent approved may have a significant market advantage on its competitors.