Reversal Agent for Uncontrollable Xarelto Bleeding Delayed by FDA

Although problems with uncontrollable bleeding on Xarelto and Eliquis have caused thousands of severe injuries and deaths, Federal regulators have rejected a proposed antidote for the new-generation anticoagulants, requesting additional information before approving the reversal agent as safe and effective.

Portola Pharmaceuticals issued a press release last week, announcing that it has received a Complete Response Letter (CRL) from the FDA, delaying the approval of AndexXa, which has been proposed as a reversal agent for a new class of anticoagulants, known as Factor Xa inhibitors.

The drug is designed to reverse the blood thinning effects of the anticoagulants, allowing doctors to control and stop bleeding events that may occur among users of Xarelto, Eliquis and other similar blood thinners.

While warfarin has been the go-to anticoagulant treatment for decades, Xarelto, Eliquis and other new-generation anticoagulants have been introduced in recent years as a superior alternative, indicating that they are easier to use and require less blood monitoring to maintain the proper dose. However, unlike warfarin, where the blood thinning effects of the drug can be reversed quickly with vitamin K and fresh frozen plasma if bleeding problems develop, no safe and effective antidote has been approved for use with Xarelto and Eliquis.

Since the drugs have hit the market, thousands of reports involving uncontrollable Xarelto bleeding problems have plagued the new drugs, and there are currently more than 7,000 Xarelto injury lawsuits pending nationwide, alleging that the Bayer Healthcare and Janssen Pharmaceuticals sold an unreasonably dangerous and defective anticoagulant, without warning about the lack of an available reversal agent.

AndexXa (andexanet alfa) was developed by Portola, and approval was expected last week. However, the FDA indicates that it requires additional information regarding the manufacturing of the drug, and data on whether the drug can be used with the blood thinners Savaysa and Lovenox, according to the Portola press release.

The FDA did approve Praxbind in October 2015, which is a reversal agent for the Factor Xa inhibitor Pradaxa, which was the first member of this class to hit the market. However, Portola sought approval to market AndexXa as a reversal agent for Xarelto and Eliquis, which were the second and third members of this class, respectively.

The approval of a reversal agent for Xarelto and Eliquis has been sought by the drug makers, since it is widely acknowledged that this will make the drugs substantially safer.

While Portola indicates that it is working with the FDA and remains confident in its ability to get AndexXa approved, CEO Bill Lis reportedly said in a conference call on Thursday that the FDA letter was “disappointing.”

According to allegations raised in product liability lawsuits filed against the drug makers, they never should have introduced the new generation anticoagulants before a safe and effective reversal agent was introduced, seeking damages for severe bleeds and wrongful deaths caused by bleeding problems on Xarelto and Eliquis.

A series of Xarelto bellwether trials are expected to begin early next year in the federal court system, which are designed to help parties gauge how juries may respond to certain evidence and testimony that is likely to be repeated throughout the litigation.

Thousands of Pradaxa lawsuits were filed against the makers of that competitor drug before the introduction of Praxbind, and the drug makers ultimately agreed to pay $650 million to settle about 4,000 cases.

It is widely expected that Xarelto settlements will require a substantially larger payment, given the larger market share and wider spread reports of problems among users of the controversial anticoagulant.