Abelacimab VTE ppx

Background

Phase II open-label, randomized, parallel-group trial, N=412, elective unilateral total knee arthroplasty. Compared three single doses of abelacimab vs enoxaparin. Abelacimab is a monoclonal antibody binding the catalytic domain of factor XI, locking it in the inactive zymogen conformation and preventing activation by factor XIIa or thrombin.

Interventions and follow up

Arm Aa: abelacimab 30 mg IV single dose post-op
Arm Ab: abelacimab 75 mg IV single dose post-op
Arm Ac: abelacimab 150 mg IV single dose post-op
Arm B: enoxaparin 40 mg SC once daily
Primary endpoint: VTE (asymptomatic DVT on venography days 8-12, symptomatic DVT, PE)
mFollow up: through day 30 post-op (assessments through day 110)

Results

VTE rate (Aa vs Ab vs Ac vs B): 13% vs 5% vs 4% vs 22%
Risk difference Aa vs B: -9.2%, 95%CI -19.4 to 1.1, P=.08
Risk difference Ab vs B: -16.8%, 95%CI -26 to -7.6, P<.001
Risk difference Ac vs B: -17.8%, 95%CI -26.7 to -8.8, P<.001

Adverse events

Clinically relevant nonmajor bleeding (Aa/Ab/Ac/B): 2% vs 2% vs 0% vs 0%
≥1 adverse event: 15% vs 15% vs 15% vs 13%

Conclusions

Factor XI inhibition with abelacimab showed noninferiority at 30 mg and superiority at 75 mg and 150 mg vs enoxaparin for VTE prevention after total knee arthroplasty, with low bleeding, supporting factor XI as a target that uncouples thrombosis from bleeding.

Key Limitations

Phase II, open-label; surrogate venographic VTE endpoint; small N per arm; single elective-surgery setting limits generalizability; not powered for clinical efficacy or rare bleeding outcomes.

Clinical Context

Proof-of-concept for factor XI/XIa inhibitors as next-generation anticoagulants. Abelacimab and related agents (e.g., asundexian, milvexian) are in phase III development for AF and VTE; not yet FDA approved.

References