Reversal agents in development for the new oral anticoagulants.
The new oral anticoagulants have many advantages over vitamin K antagonists, but they are still associated with a troublesome incidence of major bleeding. Additionally, the absence of a reversal agent for the new oral anticoagulants is a barrier to their more widespread use. Currently, there are 3 potential reversal agents in development: idarucizumab is a humanized murine monoclonal antibody fragment directed specifically at dabigatran; andexanet alfa is a recombinant modified decoy factor Xa that binds to factor Xa inhibitors; and PER977 is a small molecule that binds to factor Xa and IIa inhibitors and to heparin-based anticoagulants through charge interaction. These agents have undergone phase I clinical testing, appear to be well tolerated in healthy volunteers, and are effective in neutralizing their respective targets. All 3 are currently undergoing or entering into a phase II or III clinical study. This article reviews the available data for idarucizumab, andexanet alfa, and PER977.
Perosphere Inc., Danbury, CT. j.costin@perosphere.com.
James
J
Costin
Jack
J
Ansell
Bryan
B
Laulicht
Sasha
S
Bakhru
Solomon
S
Steiner
D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000925:Anticoagulants / Q000627:therapeutic use; D000991:Antithrombins / Q000627:therapeutic use; D001120:Arginine / Q000031:analogs & derivatives; D001562:Benzimidazoles / Q000037:antagonists & inhibitors; D001779:Blood Coagulation Factors; D017326:Clinical Trials, Phase III as Topic; D000069604:Dabigatran; D015951:Factor Xa / Q000627:therapeutic use; D065427:Factor Xa Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D010879:Piperazines; D011994:Recombinant Proteins / Q000627:therapeutic use; D013923:Thromboembolism / Q000517:prevention & control; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors
D061067:Antibodies, Monoclonal, Humanized; D000925:Anticoagulants; D000991:Antithrombins; D001562:Benzimidazoles; D001779:Blood Coagulation Factors; D065427:Factor Xa Inhibitors; C580915:PRT064445; D010879:Piperazines; D011994:Recombinant Proteins; D015091:beta-Alanine; C025667:prothrombin complex concentrates; D001120:Arginine; C000594745:idarucizumab; D015951:Factor Xa; D000069604:Dabigatran; C000593571:PER977