Andexanet alfa

Andexanet alfa
Clinical data
Routes of
administration		 Intravenous injection
ATC code none
Legal status
Legal status
  • Investigational
Identifiers
CAS Number 1262449-58-0
IUPHAR/BPS 7576
ChemSpider none
ChEMBL CHEMBL3301583

Andexanet alfa (PRT064445, PRT4445) is a drug under investigation as a potential antidote for factor Xa inhibitors, a group of anticoagulant (anti–blood clotting) drugs that includes rivaroxaban, apixaban and edoxaban. It is being 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, andexanet alfa corrected increases in blood loss resulting from anticoagulation by enoxaparin and fondaparinux.[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]

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. doi:10.1056/NEJMoa1510991. PMID 26559317.


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