The US Food and Drug Administration (FDA) has approved Andexxa (coagulation factor Xa [recombinant] inactivated-zhzo) to reverse the anticoagulation effects of factor Xa inhibitors when needed due to life-threatening or uncontrolled bleeding, Portola Pharmaceuticals has announced.
An estimated 4 million people are taking factor Xa inhibitors, such as rivaroxaban (Xarelto, Bayer/Janssen Pharmaceuticals) and apixaban (Eliquis, Bristol-Myers Squibb), but until now, there has been no approved reversal agent.
Last month, the FDA gave full approval to idarucizumab (Praxbind, Boehringer Ingelheim) to reverse the anticoagulant effect of dabigatran (Pradaxa, Boehringer Ingelheim) in the event of urgent surgery or life-threatening or uncontrolled bleeding.
In the United States alone, there were approximately 117,000 hospital admissions attributable to factor Xa inhibitor-related bleeding and nearly 2000 bleeding related deaths per month, according to the company’s news release, posted May 3.
“The expansion of available reversal agents for people prescribed newer oral anticoagulant therapies is crucial,” Randy Fenninger, chief executive officer of the National Blood Clot Alliance, said in the release. “The availability now of a reversal agent specific to rivaroxaban and apixaban expands choice and enables patients and providers to consider these treatment options with greater confidence.”
Andexxa was approved under the FDA’s accelerated approval pathway based on effects in healthy volunteers, and continued approval may be contingent on postmarketing studies to demonstrate an improvement in hemostasis in patients. A clinical trial comparing this agent or usual care is scheduled to start in 2019 and to be reported in 2023.
Andexxa was approved with a boxed warning for thromboembolic risks, ischemic risks, cardiac arrest, and sudden death. Treatment with the agent has been associated with serious and life-threatening adverse events, including arterial and venous thromboembolic events, cardiac arrest, sudden deaths, and ischemic events, such as myocardial infarction and ischemic stroke.
The most common adverse reactions in at least 5% of patients receiving Andexxa were urinary tract infections and pneumonia.
Additional important safety information and full prescribing information are available here.
Approval of the agent was supported by data from two phase 3 ANNEXA studies, ANNEXA-R and ANNEXA-A, which demonstrated a median decrease in anti-factor Xa activity from baseline of 97% for rivaroxaban and 92% for apixaban, according to a company news release, posted May 3.
As part of its review, the FDA also assessed interim data from the ongoing ANNEXA-4 study. Among the 185 evaluable high-risk patients in the open-label study, the agent was shown to provide effective clinical hemostasis in 83% of patients out to 12 hours, as recently reported by theheart.org | Medscape Cardiology. The median decrease in anti-factor Xa activity from baseline was 90% for rivaroxaban and 93% for apixaban.
“Today’s approval represents a significant step forward in patient care and one that the medical community has been eagerly anticipating,” ANNEXA-4 chair Stuart J Connolly, MD, McMaster University, Hamilton, Ontario, Canada, said in the release. “Andexxa’s rapid reversal of the anticoagulating effects of rivaroxaban and apixaban will help clinicians treat life-threatening bleeds, where every minute counts.”
Portola expects to launch Andexxa in early June under an early-supply program with a generation 1 product, with a broader commercial rollout expected in early 2019 upon FDA approval of its generation 2 manufacturing process, the news release states.
Andexanet alfa is also under review by the European Medicines Agency, with a decision expected in early 2019, it notes.
Follow Patrice Wendling on Twitter: @pwendl. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.
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