FDA Gives Nod to Andexanet Alfa, Reversal Agent for Rivaroxaban, Apixaban

The US Food and Drug Administration (FDA) has approved andexanet alfa (AndexXa, Portola Pharmaceuticals) as the first and only antidote for patients treated with rivaroxaban and apixaban when the reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.

Previously, the Portola product had received both Orphan Drug and Breakthrough Therapy designations from the FDA, and it was granted approval under the agency’s Accelerated Approval pathway founded on the change in anti-Factor Xa activity in healthy volunteers from baseline measurements.

“Today’s approval represents a significant step forward in patient care and one that the medical community has been eagerly anticipating,” Stuart J. Connolly, MD, the ANNEXA-4 Executive Committee chairman and professor in the Department of Medicine of the Faculty of Health Sciences at McMaster University in Hamilton, Ontario, said in a statement. “Andexxa’s rapid reversal of the anticoagulating effects of rivaroxaban and apixaban will help clinicians treat life-threatening bleeds, where every minute counts.”

The FDA made its decision on andexanet based on data from the 2 phase 3 studies, ANNEXA-R and ANNEXA-A, which evaluated the antidote’s safety and efficacy in healthy volunteers, with the median decrease in anti-Factor Xa activity from baseline reported as 97% for those on rivaroxaban and 92% for those on apixaban.

“Unlike for some other anticoagulants, there is currently no approved reversal agent for Factor Xa inhibitors,” Connolly said of the therapy at the 67^th American College of Cardiology Scientific Sessions in Orlando, Florida. “Factor Xa inhibitors are already widely used because of their excellent efficacy and safety profile. However, some physicians and patients may choose to use other anticoagulant drugs because they have a reversal agent rather than using one of the Factor Xa inhibitors. Having a safe and effective reversal agent available will benefit patients with acute bleeding.”

The ongoing ANNEXA-4 single-arm, open-label study of andexanet in patients with major bleeding was also included for the FDA’s decision. The data included 185 patients and revealed that Andexxa significantly reversed anti-Factor Xa activity when administered as a bolus, and that the reversal was sustained following a 2-hour infusion. The median decrease from baseline was 90% for rivaroxaban and 93% for apixaban.

Portola is expected to launch andexanet under an Early Supply Program with Generation 1 product in early June, according to the company. The broader commercial launch is projected in early 2019, after the FDA approves the Generation 2 manufacturing process.

“We are grateful to the patients who participated in our trials, our clinical trial collaborators, our employees and the FDA for their help in bringing this new drug to market for the benefit of patients with Factor Xa inhibitor-related bleeding,” said Bill Lis, the chief executive officer of Portola. “We are proud that Andexxa is a first-in-class medicine discovered in our labs. In addition to Bevyxxa, the first and only anticoagulant approved for extended [venous thromboembolism] prevention in acute hospitalized medical patients, Andexxa is our second FDA-approved product with the potential to save lives and have a major impact on global public health. We remain committed to our scientific leadership in the fields of thrombosis and hematologic cancers.”