Type of information: Acceptation for review of a NDA
Product name: AndexXa®(US)/ IndexXa™ (EU)
Compound: andexanet alfa
Therapeutic area: Cardiovascular diseases - Hematological diseases
- protein. Andexanet alfa, an FDA-designated breakthrough therapy, is a first-in-class recombinant, modified Factor Xa molecule. It is being developed as an antidote for patients receiving a Factor Xa inhibitor who suffer a major bleeding episode or who may require emergency surgery. Andexanet alfa acts as a Factor Xa decoy that targets and sequesters with high specificity both direct and indirect Factor Xa inhibitors in the blood. Once bound, the Factor Xa inhibitors are unable to bind to and inhibit native Factor Xa, thus allowing for the restoration of normal hemostatic processes. Andexanet alfa has the potential to address numerous clinical scenarios by allowing for flexible and controlled reversal, which can be short-acting through the administration of an IV bolus or longer-acting with the addition of an extended infusion.
Company: Portola Pharmaceuticals (USA - CA)
- reversing of the anticoagulant effect of direct or indirect factor Xa inhibitors in patients experiencing a serious uncontrolled bleeding event or who require urgent or emergent surgery
- • On December, 22, 2017, Portola Pharmaceuticals, Inc.® (Nasdaq:PTLA) today announced that the FDA will extend its review of the Biologics License Application (BLA) for AndexXa® (andexanet alfa) by 90 days. The company recently submitted additional data requested by the agency for the ongoing ANNEXA-4 study as part of the continuing review process, which constitutes an amendment to the submission. Therefore, the agency has instituted an extension to allow more time for a thorough review of the information provided and to work with the company on labeling and post-marketing commitments. In correspondence dated and issued today, the FDA communicated that the action date will move from February 3, 2018 to May 4, 2018 .
- Andexanet alfa is also under review by the European Medicines Agency (EMA). A final decision by the European Commission on the marketing authorization application (MAA) for andexanet alfa is anticipated in the first half of 2018.
- • On August 15, 2017, Portola Pharmaceuticals announced that the FDA has found its resubmitted Biologics License Application (BLA) for AndexXa® (andexanet alfa) to be acceptable for review, with an action due date of February 2, 2018. The resubmission includes supplemental information primarily related to analytics and manufacturing, as requested by the FDA in a complete response letter issued to Portola last year.
- • On August 3, 2017, Portola Pharmaceuticals announced that it has resubmitted its Biologics License Application (BLA) to the FDA for AndexXa® (andexanet alfa). The resubmission includes supplemental information primarily related to manufacturing, as requested by the FDA in a complete response letter issued to Portola in August 2016 (see below).•
- • On August 19, 2016, Portola Pharmaceuticals announced that the MAA for IndexXa™ (andexanet alfa) has been submitted to the EMA, completed the validation period, and has been accepted for review. Portola is seeking conditional approval of IndexXa™ in the EU through the centralized procedure. With the acceptance of the application, the EMA’s Committee for Medicinal Products for Human Use (CHMP) will now begin the centralized review procedure under a standard 210-day review period. Portola’s MAA submission is based on data from two Phase 3 Annexa™ studies that evaluated the safety and efficacy of andexanet alfa in reversing the anticoagulant activity of the Factor Xa inhibitors rivaroxaban and apixaban in healthy volunteers. Results of the ANNEXA studies were published by The New England Journal of Medicine. The MAA also included limited adjudicated efficacy and safety data from initial patients enrolled in the ongoing ANNEXA-4 study. Portola is currently evaluating andexanet alfa in this global, Phase 3b/4 single-arm, open-label study in patients receiving apixaban, rivaroxaban, edoxaban or enoxaparin who present with an acute major bleed. The study is enrolling patients in the United States, Canada and the EU.
- • On August 17, 2016, Portola Pharmaceuticals announced that it has received a Complete Response Letter (CRL) from the FDA regarding its Biologics License Application (BLA) for AndexXa™ (andexanet alfa). In the CRL, the FDA requested that Portola provide additional information primarily related to manufacturing. The agency also asked for additional data to support inclusion of edoxaban and enoxaparin in the label, and indicated it needs to finalize its review of the clinical amendments to Portola’s post-marketing commitments that recently were submitted.
- • On February 17, 2016, Portola Pharmaceutical announced that the Center for Biologics Evaluation and Research (CBER) of the FDA has accepted the Biologics License Application (BLA) for andexanet alfa for filing under a priority review. Portola submitted the BLA in December 2015 under an Accelerated Approval pathway. The FDA is expected to take action on the application by the Prescription Drug User Fee Act (PDUFA) action date of August 17, 2016.
- The BLA is based on data from preclinical, Phase 1 and 2, manufacturing and Phase 3 studies. The Phase 3 Annexa™ (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of FXa Inhibitors) studies evaluated the safety and efficacy of andexanet alfa in reversing the anticoagulant activity of the Factor Xa inhibitors rivaroxaban and apixaban in healthy volunteers. Results of those studies were published by The New England Journal of Medicine in November 2015.
- • On February 23, 2015, the FDA has granted orphan drug designation for andexanet alfa for reversing the anticoagulant effect of direct or indirect factor Xa inhibitors in patients experiencing a serious uncontrolled bleeding event or who require urgent or emergent surgery
Submission of marketing authorization application USA : 2015-12-00/2017-08-03
Submission of marketing authorization application UE: 2016-08-19
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA: 2015-02-23
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: