Abelacimab substantially lowers bleeding risk compared with rivaroxaban 

In the phase 2b AZALEA-TIMI 71 trial, abelacimab significantly reduced bleeding events compared with rivaroxaban in patients with atrial fibrillation (AF). Furthermore, the agent showed potent inhibition of factor XI. Whether this novel agent also reduces the risk of ischaemic events compared with other anticoagulants requires further study. 

The multicentre, randomised, active-controlled AZALEA-TIMI 71 trial (NCT04755283) compared the bleeding profile of the factor XI inhibitor abelacimab with the direct oral anticoagulant (DOAC) rivaroxaban in patients with AF and a moderate-to-high risk of stroke. The participants (n=1,287) were randomised in a 1:1:1 fashion to receive 90 mg or 150 mg abelacimab, subcutaneously administered once per month, or 20 mg rivaroxaban, orally administered once daily. The primary endpoint was major or clinically relevant non-major (CRNM) bleeding. Dr Christian Ruff (Brigham and Women’s Hospital, MA, USA) presented the key findings [1].

“The trial was terminated early because the data-monitoring committee reported that abelacimab yielded a larger than anticipated reduction in the primary endpoint compared with the active comparator,” announced Dr Ruff. At the time of termination, abelacimab displayed a factor XI inhibition of >95% in both dose groups. Further, the occurrence of major or CRNM bleeding was significantly lower in the 90 mg group (HR 0.23; 95% CI 0.13–0.42; P<0.0001) and the 150 mg group (HR 0.33; 95% CI 0.19–0.55; P<0.0001) than in the rivaroxaban group (see Figure).

Figure: Primary endpoint of major or CRNM bleeding in the AZALEA-TIMI 71 trial [1]

CRNM, clinically relevant non-major.

No significant difference was observed in the risk of stroke or systemic embolism between the rivaroxaban group and either the 90 mg abelacimab group (HR 1.13; 95% CI 0.41–3.12; P=0.81) or the 150 mg group (HR 1.45; 95% CI 0.55–3.80; P=0.45). “However, the rates of these events were low and were only evaluated as exploratory endpoints,” commented Dr Ruff. Finally, there were no substantial differences between the safety profiles of the 2 agents.

In summary, abelacimab 150 mg (i.e. the dose being investigated in phase 3 trials) was associated with a 67% reduction in major or CRNM bleeding compared with rivaroxaban, a decrease of 74% in major bleeding, and a reduction of 93% in major gastrointestinal bleeding. “A phase 3 trial testing abelacimab for the primary endpoint of ischaemic stroke or systemic embolism in a population of patients with AF deemed ineligible for currently available anticoagulants is underway,” Dr Ruff ended his presentation.

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   1. Ruff CT, et al. A multicentre randomised active-controlled study to evaluate the safety and tolerability of two blinded doses of abelacimab compared with open-label rivaroxaban in patients with atrial fibrillation. LB05, AHA Scientific Sessions 2023, 11–13 November, Philadelphia, USA.

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Posted on 29 January 202429 January 2024