The U.S. FDA has approved coagulation factor Xa (recombinant), inactivated-zhzo (Andexxa) for patients treated with rivaoxaban and apixaban, when reversal of anticoagulation is necessary due to fatal or uncontrolled bleeding.
The U.S. Food and Drug Administration (FDA) has approved coagulation factor Xa (recombinant), inactivated-zhzo (Andexxa) for patients treated with rivaoxaban and apixaban, when reversal of anticoagulation is necessary due to fatal or uncontrolled bleeding.
With the news, Portola Pharmaceuticals’ drug becomes the first and only antidote approved for the indication. It was previously granted both U.S. Orphan Drug and FDA Breakthrough Therapy designations, and was approved under the FDA’s Accelerated Approval pathway based on changes from baseline in anti-Factor Xa activity in healthy volunteers.
Continued approval for this indication may be contingent upon post-marketing study results to exhibit an improvement in hemostasis in patients.
The approval is reinforced by data from a pair of Phase 3 ANNEXA studies — ANNEXA-R and ANNEXA-A – published in The New England Journal of Medicine, which assessed the safety and efficacy of the therapy in overturning the anticoagulant activity of the Factor Xa inhibitors rivaroxaban and apixaban in healthy volunteers. As described in the label, results revealed that andexXa alfa quickly and meaningfully reversed anti-Factor Xa activity. The median decrease in anti-Factor Xa activity from baseline was 97% for rivaroxaban and 92% for apixaban.
“Today’s approval represents a significant step forward in patient care and one that the medical community has been eagerly anticipating,” said Stuart J. Connolly, M.D., ANNEXA-4 Executive Committee chairman and professor in the Department of Medicine of the Faculty of Health Sciences at McMaster University in a press release. “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 also assessed interim data from the ongoing ANNEXA-4 single-arm, open-label study in patients with major bleeding as part of its review and approval. Data from 185 evaluable patients demonstrated that Andexxa quickly and meaningfully reversed anti-Factor Xa activity when dosed as a bolus and this reversal was sustained when followed by a 2-hour infusion. The median decrease from baseline was 90% for rivaroxaban and 93% for apixaban.
“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, chief executive officer of Portola.
“The expansion of available reversal agents for people prescribed newer oral anticoagulant therapies is crucial,” added Randy Fenninger, chief executive officer of the National Blood Clot Alliance, a patient-led, voluntary health advocacy organization. “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.”
The post-marketing requirement is a clinical trial that randomizes patients to be administered either Andexxa or the typical standard of care. This study is scheduled to be initiated in 2019 and be reported in 2023. The company has stated its intnetions to remain consistent with its original plan, and expects to launch the drug under an Early Supply Program with Generation 1 product in early June.
Broader commercial launch is anticipated in early 2019 upon FDA approval of its Generation 2 manufacturing process.