The FDA announced that it will push back its decision on whether to approve the reversal agent AndexXa to May 4, 2018. The original review date was set for February 3, 2018, but the FDA wanted to consider additional information it had requested from Portola, the drug’s manufacturer.
Risk of Bleeding Events
It is widely known that direct oral anticoagulants (DOACs) such as Pradaxa (dabigatran), Xarelto (rivaroxaban), Savaysa (edoxaban), and Eliquis (apixaban) have the potential to cause severe and life-threatening bleeding events. These adverse side effects include intracranial hemorrhages, intra-abdominal bleeding, and other major bleeds.
According to a recent MedScape article, major bleeding is defined as:
[B]leeding that is associated with hemodynamic compromise, occurs in an anatomically critical site, requires transfusion (>2 U of packed red blood cells), or results in a hemoglobin drop >2 g/dL.
“Critical sites” include in the brain, central nervous system, heart, airways, abdomen, and extremities.
Despite the large number of bleeds that have already occurred among patients taking DOACs, the only drug for which a specific, FDA-approved antidote exists is Pradaxa. This reversal agent is called Praxbind, and is manufactured by Boehringer Ingelheim Pharmaceuticals.
Treatment of Major Bleeding Events
To address the lack of FDA-approved specific antidotes for Xarelto, Savaysa, and Eliquis, the American College of Cardiology (ACC) released information designed to help doctors stop and reverse major bleeds that result from these DOACs. The article was titled, “2017 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants.”
Here is one of six flow charts contained within the ACC document (click on image to enlarge):
The other flow charts provided in this document provide guidelines on how to treat specific kinds of bleeds pertaining to location of bleed and the DOAC taken by the patient. They also discuss determining whether to restart DOAC treatment after a bleeding event.
New Reversal Agent
Doctors may soon have another treatment option if the FDA approves the new reversal agent Portola Pharmaceuticals has been working on for Eliquis, Savaysa, and Xarelto. This antidote is called AndexXa, and is described as a “recombinant protein designed to reverse the anticoagulant effect in patients treated with oral or injectable Factor Xa inhibitors.”
It was first evaluated by the FDA in August 2016, but was not immediately approved. Instead, the FDA issued a Complete Response Letter (CRL) requesting additional information prior to approving AndexXa. A press release from Portola’s website states the following:
In the CRL for AndexXa, the FDA requested that Portola provide additional information primarily related to manufacturing. The agency also asked for additional data to support inclusion of edoxaban and enoxaparin in the label, and indicated it needs to finalize its review of the clinical amendments to Portola’s post-marketing commitments that recently were submitted.
After completing a second review of AndexXa, the FDA will make their decision on whether to formally approve the DOAC reversal agent on February 3, 2018. The press release goes on to describe what approval would mean for AndexXa and its manufacturer:
The FDA granted AndexXa Orphan Drug designation, for which Portola would expect to receive seven years of marketing exclusivity if the drug is approved. This designation applies to drugs and biologics intended for the treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the United States.
We will continue to monitor the medical literature for more information on AndexXa’s potential approval, as well as any other news pertaining to oral anticoagulants such as Xarelto, Savaysa, Eliquis, and Pradaxa.
Written by: Heather Helmendach, Legal Assistant
Law Offices of Thomas J. Lamb, P.A.
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