Key result
Idarucizumab, andexanet alfa, and PER977 are reversal agents in development for new oral anticoagulants that appear well tolerated and effective in neutralizing their targets in phase I testing.
Why the study?
Do reversal agents (idarucizumab, andexanet alfa, PER977) effectively neutralize new oral anticoagulants?
Do reversal agents (idarucizumab, andexanet alfa, PER977) effectively neutralize new oral anticoagulants?
Three potential reversal agents for new oral anticoagulants (idarucizumab, andexanet alfa, and PER977) are in development and show promise in early clinical testing, which may overcome a major barrier to the widespread use of these anticoagulants.
Phase I data support further development; leaves open real-world efficacy and safety for NOAC reversal.
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.
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Costin et al. (2014) conducted a review in Bleeding associated with new oral anticoagulants. Reversal agents (idarucizumab, andexanet alfa, and PER977) was evaluated. Idarucizumab, andexanet alfa, and PER977 are reversal agents in development for new oral anticoagulants that appear well tolerated and effective in neutralizing their targets in phase I testing.
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