The US Food and Drug Administration (FDA) has approved asundexian (Sunharbo), the first factor XIa inhibitor, for reducing stroke risk in adults following a recent noncardioembolic ischemic stroke or high-risk transient ischemic attack (TIA).
The agency announced the approval on November 9, granting it to Bayer HealthCare Pharmaceuticals. The 50-mg oral tablet is approved for once-daily use in combination with antiplatelet therapy in patients with a recent ischemic stroke and a National Institutes of Health Stroke Scale score of 15 or lower, or a high-risk TIA. The indication does not extend to stroke prevention in patients with atrial fibrillation.
According to the FDA-approved prescribing information, asundexian inhibits activated factor XI, reducing amplification of thrombin generation and thrombus formation through the intrinsic coagulation pathway.
The approval was supported by OCEANIC-STROKE, a multicenter, randomized, double-blind, placebo-controlled phase 3 trial involving 12,327 adults. Within 72 hours of symptom onset, participants were assigned to asundexian 50 mg once daily (n = 6,162) or placebo (n = 6,165), both added to antiplatelet therapy.
The primary efficacy endpoint was time to first ischemic stroke. According to the prescribing information, ischemic stroke occurred in 6.2% of asundexian recipients versus 8.4% of placebo recipients, representing a 26% relative risk reduction. Median treatment duration was 14.2 months.
The rate of major bleeding was similar between groups (1.6 vs 1.5 events per 100 person-years). However, the prescribing information reports higher rates of major bleeding with asundexian among patients older than 75 years (2.6 vs 1.7 per 100 person-years) and during the first 90 days of treatment (4.5 vs 3.1 per 100 person-years). Gastrointestinal bleeding was also more frequent (2.7 vs 2.1 events per 100 patient-years). Diarrhea occurred in 3.4% versus 2.8% of patients, and hepatic enzyme elevations were reported more frequently with asundexian.
The prescribing information lists no contraindications and does not recommend routine coagulation monitoring. It advises against concomitant use with combined P-glycoprotein and strong CYP3A4 inducers, including carbamazepine, because of potentially reduced efficacy. Use is also not recommended in patients with moderate or severe hepatic impairment.
The label also recommends withholding asundexian for at least 24 hours before elective procedures, with treatment resumed once adequate hemostasis is established. Treatment should be withheld for at least 24 hours after thrombolysis for acute ischemic stroke.
Sources: FDA, FDA Prescribing Information
