Reversal Agent for Pradaxa Bleeds Given “Breakthrough” Status by FDA

Federal drug regulators are granting “breakthrough status” to fast-track the approval process for a possible antidote to the blood thinner Pradaxa, which may help doctors control bleeding events that have caused many users to suffer serious injury or death.  

On Thursday, Boehringer Ingelheim announced that the FDA has granted its investigational Pradaxa reversal agent, idarucizumab, Breakthrough Therapy Designation. This means that the drug will go to the front of the line for development and review in hopes of getting it to the market more rapidly.

If successful and approved, the drug would be the first approved reversal agent for Pradaxa or any of the new generation of blood thinners, which also includes Xarelto. These medications have been promoted as superior to warfarin, because they are easier to use and require less frequent monitoring during treatment. However, doctors have reported uncontrollable bleeding problems with Xarelto and Pradaxa, which have made the drugs among the most commonly cited in adverse event reports submitted to the FDA.

According to Boehringer Ingelheim, a Phase I study showed that the drug, a fully humanized antibody fragment, immediately and completely reversed the anticoagulant effects of Pradaxa. The company is currently enrolling subjects in the Phase III trials.

“Boehringer Ingelheim is pleased that the FDA has granted Breakthrough Therapy Designation for idarucizumab to help expedite its development,” Sabine Luik, M.D., senior vice president, Medicine & Regulatory Affairs, said in a press release. “We are committed to innovative research and to advancing care in patients taking PRADAXA. We continue to investigate the potential of idarucizumab as a therapeutic option should a patient experience uncontrolled bleeding or need to undergo emergency surgery or another invasive procedure.”

The company said it will seek an additional Accelerated Approval process to move the antidote to the market as fast as possible, but denied it was concerned about the drug’s safety profile.

Pradaxa and Xarelto Bleeding Concerns

Pradaxa (dabigatran) was first approved by the FDA in October 2010 for the prevention of strokes among patients with atrial fibrillation. It was the first in a new class of blood thinners designed to compete with warfarin, which had dominated that market for decades.

However, shortly after its release, Pradaxa racked up a large number of adverse event complaints by doctors and patients who saw incidents of Pradaxa bleeding that could not be stopped. Unlike warfarin, whose anticoagulant effects can be reversed using vitamin K, Pradaxa has had no approved reversal agent. That meant that doctors did not have a go-to technique to stop Pradaxa bleeding events.

Xarelto (rivaroxaban) was introduced in late 2011 and has grown to surpass Pradaxa in both use and the number of adverse events submitted to the FDA involving bleeding problems.

Both the makers of Pradaxa and Xarelto have been working to develop an effective reversal agent, which is likely to provide the drug with a clear market advantage.

Boehringer Ingelheim recently agreed to pay $650 million to settle about 4,000 Pradaxa lawsuits filed on behalf of former users who suffered severe injury or death after bleeding events that doctors were unable to stop. The complaints all involved allegations that the drug maker failed to adequately warn about the bleeding risks or the lack of an effective reversal agent.

A growing number of Xarelto bleeding lawsuits are also being pursued against Bayer and Johnson & Johnson, raising similar allegations that patients suffered severe or fatal bleeding due to the manufacturers failure to warn about the lack of a reversal agent. The drug makers are also researching potential Xarelto antidotes.