Asundexian Receives FDA Approval, Becomes First FXIa Inhibitor for Secondary Stroke Risk Reduction

The FDA approved asundexian (Sunharbo; Bayer) 50 mg tablets, the first factor XIa (FXIa) inhibitor for use in combination with antiplatelet therapy to reduce the risk of stroke in adults following a recent mild-to-moderate noncardioembolic ischemic stroke—a stroke caused by a clot that did not originate in the heart—or a high-risk TIA, often called a “mini-stroke.”¹

“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 news release. “[This] approval represents a meaningful advance for patients and health care providers seeking a new option for secondary stroke prevention.”

Residual Risk Despite Antiplatelet Therapy

Despite current secondary prevention strategies, an estimated 5.1% of patients with an ischemic stroke or TIA have a recurrent stroke within 1 year, and approximately 22% of those who survive a minor stroke or TIA are dead or disabled 5 years later.² Dual antiplatelet therapy is recommended for 21 to 90 days after a minor ischemic stroke or TIA, but long-term use is associated with more major hemorrhage than monotherapy without a lower risk of stroke.² Recurrent ischemic strokes also tend to be more disabling and carry a higher mortality risk than first events.³

When the topline results were announced, the principal investigator of the phase 3 OCEANIC-STROKE trial (NCT05686070), Mike Sharma, MD, director of the Stroke Program at Hamilton Health Sciences, noted that recurrent stroke remains a significant risk even with available therapies and that “each recurrence can have profound consequences.”³

Factor XI, which is part of the intrinsic coagulation pathway, appears to play only a minor role in hemostasis. Genetic factor XI deficiency is associated with a lower risk of ischemic stroke without an increase in intracerebral bleeding, making it an attractive target for stroke prevention. At 50 mg daily, asundexian inhibits activated factor XI by more than 90%.²

OCEANIC-STROKE Trial Design

Approval was based on OCEANIC-STROKE, which was trial data from double-blind, event-driven, randomized, placebo-controlled conducted at 702 centers in 37 countries.^1,2,4 Adults were eligible within 72 hours of a noncardioembolic ischemic stroke with a National Institutes of Health Stroke Scale (NIHSS) score of 15 or lower, or a high-risk TIA (ABCD² score of 6 or 7). All patients also had at least 1 of the following: an acute nonlacunar infarct on imaging, a history of atherosclerosis, or imaging evidence of cerebrovascular atherosclerosis.² Patients with atrial fibrillation or another indication for anticoagulation were excluded from the trial.^2,4

Patients were randomly assigned 1:1 to asundexian 50 mg once per day (n = 6162) or placebo (n = 6165), in addition to planned dual or single antiplatelet therapy.² The mean age was about 68 years, approximately 24.9% of patients were older than 75 years, and 33.3% were women. Ischemic stroke was the index event in about 94.7% of patients, 27.4% of whom had received intravenous thrombolysis, endovascular therapy, or both. Dual antiplatelet therapy was planned for 62.6%.²

Efficacy Results

Ischemic stroke, the primary efficacy outcome, occurred in approximately 6.2% (n = 384) of patients who received asundexian and 8.4% (n = 518) receiving placebo (cause-specific HR, 0.74; 95% CI, 0.65-0.84; P < .001), a 26% relative risk reduction.^1,2 Effects were mostly consistent across prespecified subgroups, including patients older than 75 years (HR, 0.72).²

Additionally, asundexian also reduced the first 3 secondary outcomes in the testing hierarchy²:

• Any stroke (ischemic or hemorrhagic): 6.6% vs 8.8% (HR, 0.74; 95% CI, 0.65-0.84; P < .001)
• Cardiovascular death, myocardial infarction (MI), or stroke: 9.2% vs 11.1% (HR, 0.83; 95% CI, 0.74-0.92; P < .001)
• All-cause death, MI, or stroke: 10.5% vs 12.3% (HR, 0.85; 95% CI, 0.77-0.95; P = .003)

The investigators wrote that the reduction in ischemic stroke within the first 90 days was not considered significant (3.0% vs 3.5%; HR, 0.84; 95% CI, 0.69-1.02; P = .08), so formal hypothesis testing stopped there. Among the remaining outcomes, disabling or fatal stroke occurred in approximately 2.1% vs 3.0% of patients (HR, 0.69), and all-cause mortality was similar (4.0% vs 4.1%).²

Safety Profile

International Society on Thrombosis and Haemostasis major bleeding occurred in 1.9% (n = 117) of those who received asundexian and 1.7% (n = 107) of those who received placebo (HR, 1.10; 95% CI, 0.85-1.44).² Rates of major or clinically relevant nonmajor bleeding (5.5% vs 5.0%), symptomatic intracranial hemorrhage (0.7% vs 0.6%), hemorrhagic stroke (0.2% vs 0.3%), and fatal bleeding (0.2% vs 0.1%) were also similar.² Adverse events (AEs; 69.3% vs 70.1%), serious AEs (19.2% vs 19.5%), and permanent discontinuation (26.5% vs 26.1%) were comparable between groups.²

The FDA noted that major bleeding was increased with asundexian in patients older than 75 years and during the first 90 days of treatment. Gastrointestinal bleeding was more common with asundexian, and diarrhea was the most frequently reported adverse reaction, occurring in at least 3% of treated patients.¹

The investigators acknowledged that relatively few patients had an NIHSS score of 8 or higher, only about 5% enrolled after a high-risk TIA, and Black patients made up 2.3% of the population.²

When reviewing asundexian therapy, pharmacists should note that concomitant use with combined P-glycoprotein and strong CYP3A4 inducers, such as carbamazepine, is not recommended because these agents may reduce its effectiveness. Pharmacists should also counsel patients on signs of bleeding—particularly gastrointestinal bleeding—with added attention for older adults and those in the first 90 days of therapy, given the higher bleeding risk the FDA identified in these groups.¹

REFERENCES

1. FDA approves first factor XIa inhibitor to help prevent stroke in certain adults at high risk. News release. FDA. November 9, 2026. Accessed November 10, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-factor-xla-inhibitor-help-prevent-stroke-certain-adults-high-risk

2. Sharma M, Dong Q, Hirano T, et al; OCEANIC-STROKE Investigators. 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 November 10, 2026. https://www.bayer.com/en-us/united-states/news-and-stories/2025/oceanic-stroke

4. A study to test asundexian for preventing a stroke caused by a clot in participants after an acute ischemic stroke or after a high-risk transient ischemic attack, a so-called mini stroke (OCEANIC-STROKE). ClinicalTrials.gov identifier: NCT05686070. Accessed November 10, 2026. https://clinicaltrials.gov/study/NCT05686070