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37360711000001100

Refrigerated Storage

OndexxyaAlexion Pharma UK Ltd

Alexion Pharma UK Ltd
Ondexxya
200 mg powder for solution for infusion

Contact Alexion Pharma UK Ltd in all cases where a deviation from the recommended storage conditions has occurred. Refer to the current BNF for company contact details.
Please also refer to the manufacturer’s product literature for recommended storage information at https://www.medicines.org.uk

7 October 2021

New Medicines

OndexxyaAnticoagulation reversal - antidote to edoxaban

Information

Ondexxya
Licence extension / variation
Portola Pharmaceuticals
Portola Pharmaceuticals

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Not approved
Oct 21Alexion receive a Complete Response Letter from US FDA for its sBLA to extend the indication to include pts treated with edoxaban or enoxaparin, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding. Alexion is reviewing the letter and evaluating next steps. [10]
Jul 21Alexion Pharmaceuticals is acquired by AstraZeneca [7]
Dec 20Alexion submitted a US supplemental Biologics License Application (sBLA) for a label expansion for the reversal of edoxaban and enoxaparin associated bleeds.[9]
Jul 20Portola Pharmaceutical is acquired and merged into Alexion Pharmaceuticals [7]
Jun 20Extensions of the ANNEXA-4 study, are enrolling patients in Germany and Japan. The purpose of the extensions is to gain experience with patients receiving edoxaban and with Japanese patients [6].
Jun 20Portola anticipates Andexxa approval as a reversal agent to edoxaban in late 2022 [5].
Nov 19Portola anticipates Andexxa approval as a reversal agent to edoxaban in the US and Europe to be achieved in 2020 [4]
Jul 14Portola enters into a clinical collaboration agreement with Daiichi Sankyo, to conduct PIII trials of andexanet alfa to reverse the anticoagulant effects of edoxaban [2].

Category

Factor Xa inhibitor antidote. First-in-class recombinant, modified Factor Xa molecule that directly reverses the effects of Factor Xa inhibitors.
It has been estimated that around 1-4% of pts treated with Factor Xa inhibitors may experience major bleeding and 1% may require emergency surgery. Development of a specific antidote designed to reverse the anticoagulant activity of Factor Xa inhibitors may provide an important treatment option for pts who experience a major bleeding event or require emergency surgery [10].
Anticoagulation reversal - antidote to edoxaban
Intravenous

Trial or other data

Aug 19Two PII studies are now complete. PII (NCT03310021) study was a single-center, randomised, double-blind, and placebo-controlled trial designed to: 1) demonstrate the degree to which administered andexanet doses can reverse Factor Ten A (FXa)-inhibitor induced anticoagulation; and 2) evaluate the safety and PK/PD of andexanet in healthy subjects taking direct FXa inhibitors at therapeutic doses. 108 subjects were recruited in the US. PII (NCT03551743) study aimed to evaluate the ability of PRT064445 to reverse the effects of several blood thinner drugs on laboratory tests. The study also is evaluating the blood levels of PRT064445 given at different doses. 28 subjects were enrolled [3]
Apr 19A mutli-centre prospective open-label PIII trial (ANNEXA-4, NCT02329327) evaluated the haemostatis efficacy of andexanet alfa in pts received a factor Xa inhibitor (apixaban, rivaroxaban, edoxaban and enoxaparin) who were experiencing an acute major bleed (n=479). Results of 352 pts are published in the New England Journal of Medicine. Primary outcome measures include % change from baseline in anti-factor Xa activity by the factor Xa inhibitor and pts achieving haemostatic efficacy 12 hours post infusion. Anti-factor Xa activity was demonstrated to be reduced after administration of andexanet alfa. 82% of pts had excellent or good haemostatic efficacy at 12 hours. Within 30 days, death occured in 14% of pts and 10% experienced a thrombotic event [8]