Phase 3 OCEANIC-STROKE trial shows asundexian cut recurrent ischemic stroke

Asundexian in combination with antiplatelet therapy reduced recurrent ischemic stroke compared to antiplatelet therapy alone in patients with recent noncardioembolic ischemic stroke or high-risk transient ischemic attack. There was no significant difference in major bleeding between the two groups. The phase 3, double-blind, randomized controlled trial evaluated the efficacy and safety of the oral factor XIa inhibitor in 12,327 patients enrolled within 72 hours of symptom onset.

Patients were randomized in a 1:1 fashion to receive asundexian 50 mg daily or placebo, in addition to background single or dual antiplatelet therapy, and were followed for a median duration of 567 days. The primary efficacy outcome, recurrent ischemic stroke, occurred in 6.2% of patients receiving asundexian compared to 8.4% in the placebo group, corresponding to a hazard ratio of 0.74 (95% confidence interval, 0.65 to 0.84; p<0.001).

Secondary outcomes also favored the asundexian group, including a reduction in the composite of cardiovascular death, myocardial infarction, or stroke (9.2% vs. 11.1%; HR, 0.83; p<0.001) and in any stroke (6.6% vs. 8.8%; HR, 0.74; p<0.001). However, the reduction in ischemic stroke within the first 90 days did not reach statistical significance (HR, 0.84; p=0.08), suggesting that treatment effects may accrue over longer follow-up.

The primary safety outcome, major bleeding, was similar between groups (1.9% vs. 1.7%; HR, 1.10; 95% CI, 0.85 to 1.44). Rates of intracranial hemorrhage, hemorrhagic stroke, and fatal bleeding were also comparable. Subgroup analyses were consistent across age, sex, stroke subtype, and use of dual antiplatelet therapy.

Asundexian is a novel investigational treatment that inhibits a clotting protein called Factor XI (FXIa). Overall, asundexian was associated with superior secondary ischemic stroke prevention without increased risk of major bleeding.