FDA Approves Asundexian: A New Era in Secondary Stroke Prevention
The Food and Drug Administration approved asundexian 50 mg tablets on November 9 for adults who have suffered a recent mild-to-moderate noncardioembolic ischemic stroke or a high-risk transient ischemic attack. Marketed under the brand name Sunharbo and manufactured by Bayer, the drug functions as the first factor XIa inhibitor approved for clinical use alongside antiplatelet therapy.
Reducing Recurrent Ischemic Stroke
In the OCEANIC-STROKE trial published in the New England Journal of Medicine, adding the drug to standard antiplatelet treatment reduced recurrent ischemic stroke by 26% compared to antiplatelet therapy alone. Researchers observed no statistically significant increase in major bleeding during the investigation.
The trial assigned 12,327 patients within 72 hours of symptom onset to receive either asundexian 50 mg once daily or a placebo, combined with single or dual antiplatelet therapy. Participants required evidence of a nonlacunar infarct or atherosclerotic disease, with a median follow-up lasting approximately 19 months.
Recurrent ischemic stroke occurred in 6.2% of patients receiving the treatment compared to 8.4% of those receiving the placebo. This yielded a hazard ratio of 0.74, representing an absolute risk reduction of 2.2 percentage points over the trial period.
“The OCEANIC-STROKE findings are practice changing,” Joseph Broderick, a stroke neurologist at the University of Cincinnati, told Medscape Medical News.
Asundexian also reduced disabling strokes to 2.1% from 3.0%, with a hazard ratio of 0.69. Andrew Russman, head of the Cleveland Clinic Stroke Program, said the medication could transform secondary stroke prevention.
🚨A major breakthrough in #thrombosis prevention ! Factor 11a inhibitors are here! We now have the first ever FDA-approved Factor 11a inhibitor. The FDA just approved asundexian for secondary prevention of non-Afib stroke. Factor 11a inhibition is a brand new mechanism of…
Targeting Factor XIa for Clot Prevention
The therapy selectively inhibits activated factor XI, a protein involved in clot formation that remains less essential to normal hemostasis than factor Xa or thrombin. The approach aims to prevent harmful clots while preserving the body’s ability to stop bleeding.
Patients with noncardioembolic ischemic stroke typically receive antiplatelet therapy rather than direct oral anticoagulants because conventional anticoagulation fails to demonstrate a favorable benefit-risk balance for bleeding. The trial evaluated asundexian as an addition to antiplatelet therapy rather than a replacement.
Benefit appeared consistent across stroke subtypes, including large-artery atherosclerosis, small-vessel occlusion, and strokes of undetermined cause. Exploratory analyses indicated that this protective effect was maintained over time.
Bleeding Risks Remain Similar Between the Drug and Placebo
Major bleeding occurred in 1.9% of patients receiving the new drug and 1.7% of those taking the placebo, a difference that was not statistically significant with a hazard ratio of 1.10.
A detailed analysis published in October in Circulation showed similar rates of symptomatic intracranial hemorrhage at 0.7% versus 0.6%. Major or clinically relevant nonmajor bleeding reached 5.5% with the treatment and 5.0% with the placebo.
Gastrointestinal bleeding occurred more frequently among patients taking the medication at 3.0% compared to 2.4% for the placebo group. Lower gastrointestinal bleeding accounted for 1.7% of the treatment group and 1.0% of the control group.
The Food and Drug Administration noted in its approval announcement that major bleeding rates were higher in patients older than 75 years and during the first 90 days of treatment.
Comparing Previous Trial Outcomes
The success in stroke prevention contrasts with earlier findings in other cardiovascular settings. In November 2023, the OCEANIC-AF trial stopped early after asundexian proved substantially less effective than apixaban in preventing stroke or systemic embolism among patients with atrial fibrillation.
Event rates in the atrial fibrillation trial reached 1.3% with asundexian and 0.4% with apixaban, producing a hazard ratio of 3.79. Another trial involving milvexian, known as LIBREXIA-ACS, failed to reduce cardiovascular death, myocardial infarction, or ischemic stroke after acute coronary syndrome when added to standard antiplatelet therapy.
Russman suggested that the importance of factor XI-mediated thrombosis differs across cardiovascular conditions. Patients with factor XI deficiency exhibit similar rates of heart attack but a reduced risk of stroke.
Other Factor XI and XIa Inhibitors Undergo Clinical Trials
Other factor XI and XIa inhibitors remain in late-stage development. The LIBREXIA-STROKE trial is evaluating milvexian at 25 mg twice daily added to antiplatelet therapy for preventing recurrent ischemic stroke, with enrollment complete but efficacy results pending.
Broderick said positive results for milvexian would reinforce confidence in factor XIa inhibition as a stroke prevention strategy. Another approach involves abelacimab, a long-acting monoclonal antibody administered by monthly subcutaneous injection.
“We are already designing our trials of other medications for stroke prevention expecting that patients would already be on a factor XIa medication,” Broderick said.
Disclaimer: The information provided in this article is for educational and scientific communication purposes only and does not constitute medical advice. Always consult with a qualified healthcare provider regarding any medical condition, diagnosis, or treatment plan.
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