Anticoagulation with the mechanistically distinct FXI/FXIa antibodies amrecibart (REGN9933A2) and cenvacibart (REGN7508Cat).
Dan Chalothorn, Aaron P Kithcart, Ethan Marin et al.
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In 30 seconds
This Phase I randomised controlled trial programme evaluated two mechanistically distinct factor XI/FXIa monoclonal antibodies as potential anticoagulants, using in vitro assays, nonhuman primates and healthy volunteers. Both antibodies inhibited intrinsic pathway-triggered coagulation, with dose-dependent and durable activated partial thromboplastin time (aPTT) prolongation in volunteers, while prothrombin time (PT) was unaffected. Cenvacibart produced a greater aPTT increase than amrecibart or other FXI-targeted inhibitors. In nonhuman primates, both prevented thrombosis without increased bleeding; in first-in-human studies, both were generally well tolerated.
Key findings
- Both antibodies dose-dependently inhibited intrinsic pathway-triggered coagulation and produced durable aPTT prolongation in healthy volunteers.
- Cenvacibart caused a greater aPTT increase than amrecibart or other FXI-targeted inhibitors.
- Neither antibody affected PT, and both prevented thrombosis without increased bleeding in nonhuman primates.
- Both antibodies were generally well tolerated in first-in-human studies.
Why it matters
The findings support factor XI as a potential anticoagulation target that may inhibit thrombosis while sparing extrinsic pathway coagulation. The antibodies’ different mechanisms and degrees of aPTT prolongation suggest that they could offer distinct anticoagulant profiles. However, the reported human findings are from early-phase studies and do not establish clinical efficacy or comparative bleeding risk.
What to keep in mind
The first-in-human studies involved healthy volunteers, and the abstract does not report clinical efficacy or bleeding outcomes in patients.