FDA Approves Factor XIa Inhibitor Asundexian for Secondary Stroke Prevention

The FDA has approved Bayer's asundexian, an oral factor XIa (FXIa) inhibitor, to reduce the risk of recurrent stroke in adults following a noncardioembolic ischemic stroke or high-risk transient ischemic attack (TIA). Marketed as Sunharbo, the therapy becomes the first FXIa inhibitor approved for secondary stroke prevention.

Asundexian was approved in 50 mg tablet forms and is to be used in combination with antiplatelet therapy. The decision was based on data from the pivotal phase 3 OCEANIC-STROKE trial (NCT05686070), in which once-daily asundexian added to antiplatelet therapy reduced ischemic stroke without a statistically significant increase in major bleeding.^1,2

Asundexian is not approved for stroke prevention in patients with atrial fibrillation, and is not recommended in patients with moderate or severe hepatic impairment. According to the FDA’s release, concomitant use with medicines that are combined P-gp and strong CYP3A4 inducers are not recommended with asundexian as they may decrease the medication’s effectiveness. Additionally, the agency recommended that the therapy be withheld at least 24 hours before elective surgery or invasive procedures and for at least 24 hours after thrombolysis for acute ischemic stroke.

"Non-cardioembolic ischemic strokes account for approximately 45% of the 12 million strokes occurring globally each year. Despite guideline-recommended therapy, these patients remain at substantial risk of recurrence, with approximately 1 in 10 experiencing another stroke within one year," Ashkan Shoamanesh, MD, co–principal investigator of OCEANIC-STROKE and senior scientist at the Population Health Research Institute (PHRI), previously told NeurologyLive^®. "These findings support the potential of asundexian as a broadly applicable therapeutic option for patients with non-cardioembolic ischemic stroke or high-risk TIA who meet trial eligibility criteria."

Phase 3 Data Supporting Approval

The double-blind OCEANIC-STROKE trial randomly assigned 12,327 patients (asundexian, n = 6162; placebo, n = 6165) within 72 hours of a noncardioembolic ischemic stroke or high-risk TIA to asundexian 50 mg once daily or placebo, in addition to planned single or dual antiplatelet therapy.² Eligible patients had a National Institutes of Health Stroke Scale (NIHSS) score of 15 or less and at least 1 of the following: a nonlacunar infarct on imaging, a history of atherosclerosis, or atherosclerotic plaque on cerebrovascular imaging.

Ischemic stroke, the primary efficacy outcome, occurred in 6.2% of patients receiving asundexian vs 8.4% of those receiving placebo (cause-specific HR, 0.74; 95% CI, 0.65-0.84; P <.001). Ischemic or hemorrhagic stroke occurred in 6.6% vs 8.8%, respectively (HR, 0.74; 95% CI, 0.65-0.84; P <.001). Overall, treatment with 50 mg of asundexian significantly reduced the risk of ischemic stroke by 26% compared with placebo over a median treatment of 14.2 months.

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The key secondary composite of cardiovascular death, myocardial infarction, or stroke occurred in 9.2% of the asundexian group and 11.1% of the placebo group (HR, 0.83; 95% CI, 0.74-0.92; P <.001). The composite of all-cause death, myocardial infarction, or stroke occurred in 10.5% vs 12.3% (HR, 0.85; 95% CI, 0.77-0.95; P = .003).²

"As clinicians, we see every day how devastating a recurrent stroke can be for patients and their families. Even with currently available therapies, the risk of another stroke remains high, and each recurrence can have profound consequences," lead investigator Mike Sharma, MD, MSc, professor of medicine at McMaster University and director of the Stroke Program at Hamilton Health Sciences, said in a statement at the time of the topline results.³

Bleeding and Safety Profile

International Society on Thrombosis and Haemostasis (ISTH)–defined major bleeding, the primary safety outcome, occurred in 1.9% of patients treated with asundexian and 1.7% of those receiving placebo (HR, 1.10; 95% CI, 0.85-1.44; P = .46). Major or clinically relevant nonmajor bleeding occurred in 5.5% vs 5.0% (HR, 1.12; 95% CI, 0.96-1.30; P = .16).

Adverse events (AEs) were reported in 69.3% of the asundexian group and 70.1% of the placebo group, and serious AEs occurred in 19.2% and 19.5%, respectively.

Path to Approval and Remaining Questions

The phase 3 design was shaped by the phase 2b PACIFIC-STROKE trial (NCT04304508), which did not meet its primary end point of covert brain infarction or ischemic stroke but showed a signal for fewer symptomatic strokes with the 50-mg dose, particularly among patients with atherosclerosis, without increasing major or clinically relevant nonmajor bleeding.⁴ Those findings informed the 50-mg dose, enrichment for atherosclerotic disease, and the focus on symptomatic events in OCEANIC-STROKE. The FDA had previously granted asundexian fast track designation for secondary stroke prevention and accepted the new drug application under priority review in May 2026.⁵

The approval applies to the population studied: patients with noncardioembolic ischemic stroke or high-risk TIA who meet trial criteria. Investigators have pointed to the trial's inclusion of patients with NIHSS scores up to 15 and those who received intravenous thrombolysis or endovascular thrombectomy as support for generalizability, while the data do not address patients with cardioembolic stroke.

“Stroke is a leading cause of disability and death in the United States, and survivors are at risk of having another stroke,” Hylton V. Joffe, MD, MMSc, Director of the Office of Cardiology, Hematology, Endocrinology, and Nephrology in the FDA’s Center for Drug Evaluation and Research, said in a statement.¹ “Today’s approval represents a meaningful advance for patients and health care providers seeking a new option for secondary stroke prevention.”

Clinician Insight

Earlier this year, NeurologyLive^® convened a panel of stroke experts to discuss asundexian, OCEANIC-STROKE, and the findings behind it. In the clip below, panelists Ashkan Shoamanesh, MD, FRCPC, FESO; Gregory W. Albers, MD; James Siegler, MD; and Eva Mistry, MD, provide clinical insights on the trial and the significance of the data.

Click here to view more of our FDA coverage.

REFERENCES
1. [Title of FDA or Bayer approval announcement]. News release. [FDA/Bayer]. [Month Day, 2026]. Accessed [Month Day, 2026]. [URL]
2. Sharma M, Dong Q, Hirano T, et al. Asundexian for secondary stroke prevention. N Engl J Med. 2026;394(15):1467-1479. doi:10.1056/NEJMoa2513880
3. Bayer's asundexian met primary efficacy and safety endpoints in landmark phase III OCEANIC-STROKE study in secondary stroke prevention. News release. Bayer. November 23, 2025. Accessed [Month Day, 2026]. https://www.bayer.com/en/us/news-stories/oceanic-stroke
4. 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
5. Bayer granted priority review by U.S. FDA for asundexian in patients after a non-cardioembolic ischemic stroke or transient ischemic attack. News release. Bayer. May 18, 2026. Accessed [Month Day, 2026]. https://www.businesswire.com/news/home/20260518787299/en/Bayer-Granted-Priority-Review-by-U.S.-FDA-for-Asundexian-in-Patients-After-a-Non-Cardioembolic-Ischemic-Stroke-or-Transient-Ischemic-Attack