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.
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. The drug does not seem to be effective against the factor IIa inhibitor dabigatran.
In rats, andexanet alfa corrected increases in blood loss resulting from anticoagulation by enoxaparin and fondaparinux. A small, phase I safety and tolerability study in humans has been completed and a phase II trial is under way as of January 2014[update]. Interim results from this study showed that it reversed the action of rivaroxaban within two minutes.
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.
Other anticoagulant antidotes
- 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.
- 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.
- H. Spreitzer (23 December 2013). "Neue Wirkstoffe – Andexanet Alfa". Österreichische Apothekerzeitung (in German) (26/2013): 40.
- 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
- 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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