Andexanet alfa for the reversal of factor Xa inhibitors

J Favresse, M Hardy, M A van Dievoet, A L Sennesael, J Douxfils, C M Samama, O Vornicu, A S Dincq, S Lessire, F Mullier

Research output: Contribution to journalArticle

Abstract

INTRODUCTION: Andexanet alfa is a recombinant modified factor Xa protein that has been developed to reverse factor Xa inhibitors. Since May 2018, the FDA has approved its utilization in patients treated with apixaban and rivaroxaban in case of life-threatening or uncontrolled bleeding. On 28 of February 2019, the Committee for Medicinal Products for Human Use adopted a positive opinion, recommending the granting of a conditional marketing authorization for andexanet alfa in Europe. Area covered: The authors provide an overview of andexanet alfa development and its pharmacokinetic and pharmacodynamic properties. The results of the clinical phase III trial ANNEXA as well as current limitations related to andexanet alfa are also discussed. Expert opinion: Although phase I and II studies have proven that andexanet alfa can be effective in reversing the effect of factor Xa inhibitors, its efficacy in major bleeding patients has only been shown for apixaban and rivaroxaban, without any comparator group. Well-designed studies comparing the efficacy and safety of andexanet alfa to other reversal strategies are required to confirm preliminary data. The benefit of andexanet alfa in specific settings needs to be investigated and its use in clinical practice needs to be facilitated by the implementation of international guidelines.

Original languageEnglish
Pages (from-to)387-397
Number of pages11
JournalExpert Opinion on Biological Therapy
Volume19
Issue number5
DOIs
Publication statusPublished - 4 May 2019

Fingerprint

Pharmacodynamics
Hemorrhage
Phase III Clinical Trials
Factor Xa
Pharmacokinetics
Expert Testimony
PRT064445
Factor Xa Inhibitors
Marketing
Guidelines
Safety
Proteins
Rivaroxaban
apixaban

Keywords

  • ANNEXA
  • Andexanet alfa
  • DOACs
  • antidote
  • factor Xa
  • major bleeding
  • reversal agents

Cite this

Favresse, J ; Hardy, M ; van Dievoet, M A ; Sennesael, A L ; Douxfils, J ; Samama, C M ; Vornicu, O ; Dincq, A S ; Lessire, S ; Mullier, F. / Andexanet alfa for the reversal of factor Xa inhibitors. In: Expert Opinion on Biological Therapy. 2019 ; Vol. 19, No. 5. pp. 387-397.
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Andexanet alfa for the reversal of factor Xa inhibitors. / Favresse, J; Hardy, M; van Dievoet, M A; Sennesael, A L; Douxfils, J; Samama, C M; Vornicu, O; Dincq, A S; Lessire, S; Mullier, F.

In: Expert Opinion on Biological Therapy, Vol. 19, No. 5, 04.05.2019, p. 387-397.

Research output: Contribution to journalArticle

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AU - Favresse, J

AU - Hardy, M

AU - van Dievoet, M A

AU - Sennesael, A L

AU - Douxfils, J

AU - Samama, C M

AU - Vornicu, O

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AU - Lessire, S

AU - Mullier, F

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N2 - INTRODUCTION: Andexanet alfa is a recombinant modified factor Xa protein that has been developed to reverse factor Xa inhibitors. Since May 2018, the FDA has approved its utilization in patients treated with apixaban and rivaroxaban in case of life-threatening or uncontrolled bleeding. On 28 of February 2019, the Committee for Medicinal Products for Human Use adopted a positive opinion, recommending the granting of a conditional marketing authorization for andexanet alfa in Europe. Area covered: The authors provide an overview of andexanet alfa development and its pharmacokinetic and pharmacodynamic properties. The results of the clinical phase III trial ANNEXA as well as current limitations related to andexanet alfa are also discussed. Expert opinion: Although phase I and II studies have proven that andexanet alfa can be effective in reversing the effect of factor Xa inhibitors, its efficacy in major bleeding patients has only been shown for apixaban and rivaroxaban, without any comparator group. Well-designed studies comparing the efficacy and safety of andexanet alfa to other reversal strategies are required to confirm preliminary data. The benefit of andexanet alfa in specific settings needs to be investigated and its use in clinical practice needs to be facilitated by the implementation of international guidelines.

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