Asundexian Reduces Risk of Stroke Recurrence in Phase 3 OCEANIC-STROKE Trial

Factor XIa (FXIa) inhibition with asundexian in survivors of noncardioembolic ischemic stroke or high-risk transient ischemic attack (TIA) lowered the risk of recurrent clot-caused stroke by 26% in the phase 3 OCEANIC-STROKE trial (NCT05686070), according to final results presented at the 2026 International Stroke Conference (ISC).¹

Asundexian is a direct oral inhibitor of FXIa that is taken daily, and earlier exploratory trials have shown it to inhibit FXIa activity without increasing the risk of bleeding,² study author Mike Sharma, MD, MSc, a stroke neurologist and Michael G. DeGroote Chair in Stroke Prevention at McMaster University, explained while presenting the data at ISC 2026. OCEANIC-STROKE is the first completed phase 3 trial investigating asundexian in survivors of noncardioembolic ischemic stroke or high-risk TIA.

The rationale behind the treatment is that, because genetic FXI deficiency has been linked with reduced risk of ischemic stroke without an increased intracerebral hemorrhage risk,³ FXIa is an attractive therapeutic target for survivors of ischemic stroke.

The phase 3, double-blinded, placebo-controlled, event-driven OCEANIC-STROKE trial randomized 12,327 participants within 72 hours of mild to moderate acute non-cardioembolic ischemic stroke between January 2023 and February 2025 and followed them for at least 3 months and up to 31 months. Patients were stratified to receive either 50 mg asundexian daily (n = 6162) or a placebo (n = 6165). The mean age in the trial was 68 years, 33% of participants were female, and baseline characteristics were similar between the groups.

Participants in the study had at least 1 of the following: a history of atherosclerosis, imaging evidence of atherosclerosis in intra- or extracranial vessels, or a visualized non-lacunar infarct. Exclusion criteria were a history of nontraumatic intracranial bleeding, sources of stroke requiring anticoagulation, and active non-trivial bleeding.

For 95% of participants, the index event was ischemic stroke. Of these patients, 27% underwent intravenous thrombolysis and/or mechanical thrombectomy. Large artery atherosclerosis accounted for 43% of index strokes, and small vessel occlusion accounted for 22%. Thirty percent of index strokes were undetermined, and 2% were cardioembolic based on TOAST classification. More than half of patients were planned to receive dual antiplatelet therapy at randomization.

Ischemic stroke occurrence was the primary efficacy end point, and the primary safety end point was risk of major bleeding based on International Society on Thrombosis and Haemostasis (ISTH) criteria.

Sharma announced that patients in the asundexian group experienced significantly improved outcomes compared with placebo, including a lower risk of recurrent ischemic stroke (cause-specific HR, 0.74; 95% CI, 0.65-0.84; P < .001). When he added that the ischemic stroke cumulative incidence curves diverged early and continued to diverge throughout treatment, the main hall at the Ernest N. Morial Convention Center erupted in applause. Sharma also noted that outcomes were similar across patient subgroups.

Asundexian also demonstrated promising safety, with no significant increase in the risk of ISTH major bleeding vs placebo (csHR, 1.10; 90% CI, 0.85-1.44; P = 46). There was also a trend toward fewer disabling or fatal strokes among those in the asundexian group.

Regarding secondary efficacy end points, patients in the asundexian group experienced lower rates of ischemic or hemorrhagic stroke (csHR, 0.74; 95% CI, 0.65-0.84; P < .001); cardiovascular death, myocardial infarction, or stroke (csHR, 0.83; 95% CI, 0.74-0.92; P < .001); all-cause mortality, myocardial infarction, or stroke (csHR, 0.85; 95% CI, 0.77-0.95; P = .003); and ischemic stroke in the initial 90 days, although this trend did not reach statistical significance (csHR, 0.84; 95% CI, 0.69-1.02; P = .08).

“In patients with noncardioembolic ischemic stroke or high-risk TIA treated with antiplatelet therapy, asundexian at 50 mg once a day reduced the occurrence of ischemic stroke, with a cause-specific hazard rate of 0.74,” Sharma concluded. “The difference between treatment arms began early and continued throughout the treatment period. A consistent effect was seen across subgroups, including stroke subtypes.”

References

1. Sharma M, Joundi R, Eikelboom, et al. Factor XIa inhibition with asundexian in acute non-cardioembolic stroke or high-risk transient ischemic attack: primary results of the OCEANIC-STROKE trial. Presented at: International Stroke Conference 2026; February 4-6, 2026; New Orleans, LA. Abstract LB009.

2. Shoamanesh A, Mundl H, Smith EE, et al. Factor XIa inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke): an international, randomised, double-blind, placebo-controlled, phase 2b trial. Lancet. 2022;400(10357):997-1007. doi:10.1016/S0140-6736(22)01588-4

3. Heitmeier S, Visser M, Tersteegen A, et al. Pharmacological profile of asundexian, a novel, orally bioavailable inhibitor of factor XIa. J Thromb Haemost. 2022;20(6):1400-1411. doi:10.1111/jth.15700