FDA Approves Portola Pharmaceuticals’ Andexxa for the Reversal of Factor Xa
May 14, 2018—Portola Pharmaceuticals, Inc. recently announced that the US Food and Drug Administration (FDA) has approved the company's Andexxa (coagulation factor Xa [recombinant], inactivated-zhzo), an antidote indicated for patients treated with rivaroxaban and apixaban when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.
Andexxa received both US Orphan Drug and FDA Breakthrough Therapy designations and was approved under the FDA's Accelerated Approval pathway based on the change from baseline in antifactor Xa activity in healthy volunteers.
Portola expects to launch Andexxa under an Early Supply Program with the generation 1 product in early June. Broader commercial launch is anticipated in early 2019 upon FDA approval of its generation 2 manufacturing process.
The company advised that continued approval for this indication may be contingent upon postmarketing study results to demonstrate an improvement in hemostasis in patients. The postmarketing requirement is a clinical trial that randomizes patients to receive either Andexxa or usual care (the type of care the enrolling institution would provide in the absence of Andexxa). This study is scheduled to be initiated in 2019 and be reported in 2023.
According to the company, the approval of Andexxa is supported by data from two phase 3 ANNEXA studies (ANNEXA-R and ANNEXA-A), which were published in The New England Journal of Medicine and evaluated the safety and efficacy of Andexxa in reversing the anticoagulant activity of the factor Xa inhibitors rivaroxaban and apixaban in healthy volunteers. Results demonstrated that Andexxa rapidly and significantly reversed antifactor Xa activity. The median decrease in antifactor Xa activity from baseline was 97% for rivaroxaban and 92% for apixaban.
Additionally, interim data from the ongoing ANNEXA-4 single-arm, open-label study in patients with major bleeding were assessed by the FDA as part of its review and approval. Data from 185 evaluable patients showed that Andexxa rapidly and significantly reversed antifactor Xa activity when administered as a bolus and sustained this reversal when followed by a 120-minute infusion. The median decrease from baseline was 90% for rivaroxaban and 93% for apixaban.
Stuart J. Connolly, MD, who is ANNEXA-4 Executive Committee Chairman, commented in the company's announcement, "Today's approval represents a significant step forward in patient care and one that the medical community has been eagerly anticipating. Andexxa's rapid reversal of the anticoagulating effects of rivaroxaban and apixaban will help clinicians treat life-threatening bleeds, where every minute counts." Dr. Connolly is Professor in the Department of Medicine of the Faculty of Health Sciences at McMaster University in Hamilton, Ontario.