The study demonstrates abelacimab's potential to improve anticoagulation safety in AFIB patients

The study demonstrates abelacimab's potential to improve anticoagulation safety in AFIB patients

Promising results show that abelacimab could revolutionize anticoagulation therapy by cutting bleeding risks without compromising stroke protection for patients with atrial fibrillation.

A recently published study in theNew England Journal of MedicineEvaluated abelacimab, a monoclonal antibody targeting factor Researchers examined the ability of abelacimab to reduce bleeding events while maintaining effective stroke prevention.

background

Atrial fibrillation is the most common persistent cardiac arrhythmia and significantly increases the risk of stroke. Current treatments rely on anticoagulants such as direct oral anticoagulants (DOACs) and vitamin K antagonists, which reduce the risk of stroke but are associated with bleeding complications, particularly in the gastrointestinal tract.

Although DOACs are safer than conventional therapies in preventing intracranial hemorrhage, challenges such as undertreatment continue to occur due to concerns about bleeding risks. Factor XI, a key player in clot formation, has emerged as a promising therapeutic target because its inhibition could prevent clots without increasing bleeding risks.

People with hereditary factor XI deficiencies experience fewer clots without notable bleeding, making this route an attractive focus for safer anticoagulants. Preliminary studies using factor XI inhibitors such as abelacimab have shown promise. However, data from large-scale, long-term studies comparing them with existing therapies are limited, highlighting the need for further investigation into their safety and effectiveness.

About the study

The abelacimab dose of abelacimab close to factor XI achieved a median reduction of free factor

The study reported in the present study was a multinational, phase 2B, partially blinded, randomized trial enrolling 1,287 patients with atrial fibrillation and moderate risk of stroke. Participants were randomly assigned to one of three groups - one group received once monthly subcutaneous injections of abelacimab at 90 mg or 150 mg).

The study population included adults 55 years and older with atrial fibrillation and specific stroke risks. Notably, 92% of participants had previously received anticoagulants (mainly DOACs), reflecting a population familiar with standard therapies. Screening lasted up to four weeks, and patients were then followed monthly for safety assessments and laboratory tests. The primary endpoint was the occurrence of major or clinically significant non-major bleeding as defined by international guidelines.

Researchers also considered secondary endpoints such as major bleeding, hemorrhage, gastrointestinal bleeding, and clinical outcomes combining bleeding, stroke, embolism, and mortality.
The study monitored patients for a median of 2.1 years (interquartile range 2.0-2.3). During this time, the independent data monitoring committee recommended early termination of the trial due to a significant reduction in bleeding events with abelacimab compared to rivaroxaban.

In addition, safety assessments in the study included adverse events, injection site reactions, and antibody development, which were assessed by a blinded decision-making committee. Most participants were white, limiting generalizability to other racial groups.

Results

The results showed that abelacimab significantly reduced the risk of bleeding compared to rivaroxaban in patients with atrial fibrillation who were at moderate risk of stroke. Monthly administration of abelacimab (150 mg and 90 mg) resulted in a 62% and 69% reduction in major or clinically significant bleeding, respectively, compared to rivaroxaban.

The dual-action advantage of abelacimab blocks unlike oral inhibitors such as asundexian, enhancing clot prevention.

The incidence rates for bleeding events were 3.22 and 2.64 per 100 person-years for the 150 mg and 90 mg doses of abelacimab versus 8.38 for rivaroxaban. Notably, abelacimab was significantly lower. In addition, overall bleeding events, including minor bleeding, were also lower with abelacimab.

However, ischemic stroke rates were numerically higher but not statistically significant with abelacimab than with rivaroxaban (hazard ratios included confidence intervals 1.0), although the overall incidence was low. Hemorrhagic strokes were rare, with similar rates in all groups. Additionally, mortality rates were comparable between treatments, suggesting no significant safety concerns beyond bleeding risks.

The molecular and biochemical effects of abelacimab showed a sustained reduction in free factor XI levels, with the 150 mg dose achieving a median reduction of 99% over the study period. In addition, safety profiles were generally comparable between groups, with no differences in serious adverse events or discontinuities due to drug reactions. Injection site reactions were also rare and mild, and no patients developed antibodies to abelacimab.

Conclusions

Overall, the results suggested that abelacimab was a safer anticoagulant alternative for reducing bleeding risks while maintaining acceptable stroke prevention. The study also showed that abelacimab significantly reduced the risk of bleeding compared to rivaroxaban.

The results supported the potential of factor XI inhibitors to improve the safety profile of anticoagulant therapy. However, researchers said the numerically higher ischemic stroke rates (although not statistically significant) with abelacimab warrant further study in larger phase 3 trials to determine its long-term effectiveness and safety. Given the study's demographic limitations, they also emphasized the need for experiments in more racially diverse populations.

The paper further highlighted the distinctions between abelacimab and other factor XI inhibitors such as asundexian, noting abelacimab's dual mechanism of action and previous proof-of-concept data in thromboprophylaxis.

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