FDA Gives Portola Pharma’s Andexxa a Thumbs-up
In August 2016, the FDA rejected the drug, which is used to treat life-threatening or uncontrolled bleeding. Andexxa (andexanet alfa), which is an FDA-designated Breakthrough Therapy, was being evaluated in patients treated with a direct Factor Xa inhibitor, such as apixaban, rivaroxaban, or deoxaban, or an indirect Factor Xa inhibitor like enoxaparin when “reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.” It also had U.S. Orphan Drug classification.
The FDA’s Complete Response Letter (CRL) at the time requested more information mostly related to manufacturing activities. It also asked for more data related to including edoxaban and enoxaparin in the label.
Now the drug was approved under the FDA’s Accelerated Approval pathway based on the change from baseline in anti-Factor Xa activity in healthy volunteers. As a part of that pathway, continued approval may be contingent on post-marketing data showing improvement in hemostasis in patients.
Factor Xa inhibitors are increasingly used as anticoagulants to treat thromboembolic conditions like strokes, pulmonary embolism and venous thromboembolism (VTE). The traditional treatment is warfarin or enoxaparin, but the Factor Xa inhibitors have better efficacy and safety profiles. However, because of the increased use, hospital admissions and deaths related to uncontrolled bleeding have risen. Which is where Andexxa comes in, because it counteracts the effect of the Factor Xa inhibitors.
“Today’s approval represents a significant step forward in-patient care and one that the medical community has been eagerly anticipating,” said Stuart Connolly, ANNEXA-4 Executive Committee chairman and professor in the Department of Medicine of the Faculty of Health Sciences at McMaster University in Hamilton, Ontario, in a statement. “Andrexxa’s rapid reversal of the anticoagulating effects of rivaroxaban and apixaban will help clinicians treat life-threatening bleeds, where every minute counts.”
The approval was built on data from two Phase III ANNEXA studies, ANNEX-R and A, and was published in The New England Journal of Medicine. Interim data from the ongoing ANNEXA-4 single-arm, open-label trial in patients with major bleeding was also evaluated by the FDA as part of its review and approval.
The post-marketing requirement calls for a clinical trial that randomizes patients to receive either Andexxa or usual care. The study is expected to start in 2019 and report in 2023.
“The expansion of available reversal agents for people prescribed newer oral anticoagulant therapies is crucial,” said Randy Fenninger, chief execuctive officer of the National Blood Clot Alliance, a patient-led, voluntary health advocacy organization, in a statement. “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.”
Portola plans to launch the drug in early June under an Early Supply Program with Generation 1 product. A broader commercial launch is planned in early 2019 once the FDA approves the company’s Generation 2 manufacturing process.
The drug is also being reviewed by the European Medicines Agency (EMA). In February, the EMA’s Committee for Medicinal Products for Human Use (CHMP) cast a positive recommendation vote. A formal decision is expected by CHMP by the end of this year, with the European Commission (EC) expected to make a final decision in early 2019.