FDA Grants Priority Review to Bayer’s Asundexian for Secondary Stroke Prevention

The FDA has accepted Bayer’s New Drug Application (NDA) for asundexian, an investigational oral factor XIa (FXIa) inhibitor, and granted the therapy Priority Review for the prevention of recurrent stroke in patients following a non-cardioembolic ischemic stroke or transient ischemic attack (TIA). The regulatory submission was supported by positive findings from the pivotal phase 3 OCEANIC-STROKE trial, which demonstrated significant reductions in ischemic stroke risk without increasing major bleeding.^1,2

If approved, asundexian could become the first FXIa inhibitor indicated for secondary stroke prevention, representing a potentially important advance in antithrombotic therapy for a population that continues to face high rates of recurrent vascular events despite current standards of care.

“Secondary stroke remains a serious and persistent challenge, and the FDA’s Priority Review designation underscores the urgency of advancing potential new approaches in secondary stroke prevention,” Yesmean Wahdan, MD, senior vice president of U.S. Medical Affairs at Bayer, said in a statement.¹ “We are proud of this important milestone that builds on our long-standing commitment to innovation in anti-thrombotic therapies and look forward to collaborating with the FDA as we work to bring asundexian to patients in need.”

The FDA’s Priority Review designation shortens the agency’s target review timeline and is reserved for therapies that may offer significant improvements in the treatment, prevention, or diagnosis of serious conditions. Prior to this latest milestone, the agency granted Fast Track designation to asundexian in 2023 for secondary stroke prevention after non-cardioembolic ischemic stroke.

Published earlier this year in The New England Journal of Medicine, OCEANIC-STROKE (NCT05686070) enrolled 12,327 patients who recently experienced a non-cardioembolic ischemic stroke or high-risk TIA and randomized them to receive either asundexian 50 mg once daily or placebo in addition to antiplatelet therapy. Patients were enrolled within 72 hours of symptom onset and were required to have evidence of atherosclerotic disease, vascular plaque, or embolic-appearing infarcts on imaging.

Results showed that ischemic stroke, the primary efficacy outcome, occurred in 6.2% of patients receiving asundexian compared with 8.4% of those on placebo (cause-specific HR, 0.74; 95% CI, 0.65-0.84; P <.001). The therapy also significantly reduced the risk of ischemic or hemorrhagic stroke overall, which occurred in 6.6% of the asundexian group versus 8.8% of placebo-treated patients (HR, 0.74; 95% CI, 0.65-0.84; P <.001).²

Additional secondary analyses further reinforced the benefit of therapy. The composite outcome of cardiovascular death, myocardial infarction, or stroke occurred in 9.2% of patients treated with asundexian compared with 11.1% receiving placebo (HR, 0.83; 95% CI, 0.74-0.92; P <.001), while the composite of all-cause death, myocardial infarction, or stroke occurred in 10.5% versus 12.3%, respectively (HR, 0.85; 95% CI, 0.77-0.95; P = .003).

Importantly, the reduction in ischemic events was achieved without a statistically significant increase in major bleeding, a key concern with traditional anticoagulants. ISTH-defined major bleeding 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). Rates of major or clinically relevant nonmajor bleeding were similarly balanced between groups.²

“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 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.”

The results represented a major milestone not only for Bayer, but also for the broader FXIa inhibitor class. Interest in FXIa inhibition has grown steadily over the past decade based on observations that individuals with congenital factor XI deficiency tend to have lower thrombotic risk while experiencing comparatively modest bleeding complications.³ This has fueled the hypothesis that selectively targeting FXIa may decouple thrombosis prevention from excess bleeding risk, a longstanding challenge in vascular neurology and cardiovascular medicine.

Earlier phase 2 evidence from the PACIFIC-STROKE trial helped establish the foundation for OCEANIC-STROKE. Although PACIFIC-STROKE did not meet its primary efficacy end point, investigators observed signals suggesting reductions in symptomatic stroke, particularly among patients with atherosclerotic disease, while maintaining a favorable bleeding profile.⁴ These findings directly informed the design of the phase 3 program, including patient enrichment strategies and selection of the 50-mg dose.

“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, said in a prior statement. “The topline results from OCEANIC-STROKE indicate that asundexian may become a new treatment option to reduce this risk – representing a potential major step forward in secondary stroke prevention.”

Stroke remains the fifth leading cause of death in the United States, with approximately 795,000 strokes occurring annually. Despite modern antiplatelet and vascular risk reduction strategies, recurrent ischemic events remain common, with nearly 1 in 5 survivors experiencing another stroke within 5 years.¹ The emergence of FXIa inhibition may therefore represent a new therapeutic strategy aimed at reducing recurrent ischemic risk while minimizing bleeding liability traditionally associated with anticoagulation.

Earlier this year, NeurologyLive convened a panel of stroke experts to discuss asundexian, the global stroke-prevention trial, 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 OCEANIC-STROKE and the significance of the data.

REFERENCES
1. 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 May 19, 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
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. Kaplovitch E, Eikelboom JW, Dyal L, et al. Rivaroxaban and aspirin in patients with symptomatic lower extremity peripheral artery disease: a subanalysis of the COMPASS randomized clinical trial. JAMA Cardiol. 2021;6(1):21-29. doi:10.1001/jamacardio.2020.4390
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