Andexanet alfa

Andexanet alfa
Clinical data
Trade names AndexXa
Synonyms PRT064445, PRT4445
Routes of
administration		 Intravenous injection
ATC code
Legal status
Legal status
  • Approved
Identifiers
CAS Number
IUPHAR/BPS
ChemSpider
  • none
KEGG
ChEMBL

Andexanet alfa (trade name AndexXa) is an antidote for factor Xa inhibitors, a group of anticoagulant (anti–blood clotting) drugs that includes rivaroxaban, apixaban and edoxaban. It was approved by the FDA in May 2018 and was developed by Portola Pharmaceuticals.[1]

Mechanism of action

Andexanet alfa is a biologic agent, a modified recombinant derivative of factor Xa (fXa). It acts as a decoy receptor — it has a higher affinity to the fXa inhibitor than natural fXa, and consequently the inhibitor binds to the drug rather than to fXa itself.[1][2] The drug does not seem to be effective against the factor IIa inhibitor dabigatran.[3]

Studies

In rats anticoagulated by enoxaparin and fondaparinux, andexanet alfa was successful in completely reversing the increased blood losses to normal levels in a dose-dependent fashion.[1][2] A small, phase I safety and tolerability study in humans has been completed[1] and a phase II trial is under way as of January 2014.[4] Interim results from this study showed that it reversed the action of rivaroxaban within two minutes.[3]

In 2015, the first randomized control trial showed that andexanet alfa reversed the effects of factor Xa inhibitor drugs apixaban and rivaroxaban safely and effectively.[5]

In May 2018, Portola Pharmaceuticals announced that FDA has Approved AndexXa (First Factor Xa Inhibitor Antidote, Andexanet alfa).[6] Andexxa received both U.S. Orphan Drug and FDA Breakthrough Therapy designations and was approved under the FDA’s Accelerated Approval pathway based on the change from baseline in anti-Factor Xa activity in healthy volunteers. The approval of Andexxa is supported by data from two Phase 3 ANNEXA studies (ANNEXA-R and ANNEXA-A) published in The New England Journal of Medicine, which evaluated the safety and efficacy of Andexxa in reversing the anticoagulant activity of the Factor Xa inhibitors rivaroxaban and apixaban in healthy volunteers.[7]

Cost

Initial pricing (AWP) is $58,000 per reversal (800mg bolus + 960mg infusion, $3,300 per 100mg vial) which is markedly higher than reversal agents for other DOAC agents (Idarucizumab for use in Dabigatran reversal is $4,200 per reversal).[8]

See also

Other anticoagulant antidotes

References

  1. 1 2 3 4 Dolgin E (March 2013). "Antidotes edge closer to reversing effects of new blood thinners". Nature Medicine. 19 (3): 251. doi:10.1038/nm0313-251. PMID 23467222.
  2. 1 2 Lu G, Deguzman FR, Hollenbach SJ, et al. (March 2013). "A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa". Nature Medicine. 19 (4): 446–51. doi:10.1038/nm.3102. PMID 23455714.
  3. 1 2 H. Spreitzer (23 December 2013). "Neue Wirkstoffe – Andexanet Alfa". Österreichische Apothekerzeitung (in German) (26/2013): 40.
  4. ↑ Clinical trial number NCT01758432 for "Phase 2 Healthy Volunteer Study to Evaluate the Ability of PRT064445 to Reverse the Effects of Several Blood Thinner Drugs on Laboratory Tests" at ClinicalTrials.gov
  5. ↑ Siegal, DM (11 November 2015). "Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity". NEJM. 373: 2413–24. doi:10.1056/NEJMoa1510991. PMID 26559317.
  6. ↑ Inc., Portola Pharmaceuticals,. "U.S. FDA Approves Portola Pharmaceuticals' Andexxa®, First and Only Antidote for the Reversal of Factor Xa Inhibitors". GlobeNewswire News Room. Retrieved 2018-05-05.
  7. ↑ Siegal, Deborah M.; Curnutte, John T.; Connolly, Stuart J.; Lu, Genmin; Conley, Pamela B.; Wiens, Brian L.; Mathur, Vandana S.; Castillo, Janice; Bronson, Michele D. (2015-12-17). "Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity". New England Journal of Medicine. 373 (25): 2413–2424. doi:10.1056/nejmoa1510991. ISSN 0028-4793.
  8. ↑ "Lexi Comp Drug Information Online". 24 May 2018.


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