FDA Approves Sunharbo, First Factor XIa Inhibitor, to Reduce Recurrent Ischemic Stroke in High‑Risk Adults

The U.S. Food and Drug Administration has approved Sunharbo, Bayer’s asundexian, as the first factor XIa inhibitor cleared in the United States to help prevent recurrent ischemic stroke in certain high-risk adults. The agency said Monday the 50 mg once-daily tablet is approved for use with antiplatelet therapy in adults after a recent mild-to-moderate non-cardioembolic ischemic stroke or a high-risk transient ischemic attack, often called a TIA or “mini-stroke.”

The approval gives patients and doctors a new option for secondary stroke prevention, an area of ongoing need given the risk of another event after an initial stroke or TIA. Stroke is a major public health problem: About 795,000 people in the United States have a stroke each year, according to the Centers for Disease Control and Prevention. The approval was granted to Bayer HealthCare Pharmaceuticals Inc. of Whippany, New Jersey, and the labeled dose is 50 mg once daily.

FDA said Sunharbo is the first approved drug in the factor XIa inhibitor class for this use. The drugs are a newer type of blood thinner designed to reduce clotting through the intrinsic coagulation pathway.

The decision was backed by the phase 3 OCEANIC-STROKE trial, a multicenter, randomized, double-blind, placebo-controlled study that enrolled 12,327 adults at 702 centers in 37 countries. Patients were randomized within 72 hours of symptom onset and received asundexian or placebo on top of antiplatelet therapy. The median treatment duration was 14.2 months.

In the trial, 6.2% of patients treated with asundexian plus antiplatelet therapy had an ischemic stroke, compared with 8.4% of those given placebo plus antiplatelet therapy. FDA said that amounted to a cause-specific hazard ratio of 0.74, or a 26% relative risk reduction, a result that was statistically significant with P less than .001.

On safety, overall rates of ISTH major bleeding — a standard measure of serious bleeding in clinical trials — were similar between groups: 1.9% with asundexian and 1.7% with placebo. The hazard ratio was 1.10, with a 95% confidence interval of 0.85 to 1.44.

Still, the agency highlighted important caveats. Bleeding was increased in patients older than 75 and during the first 90 days of treatment, and gastrointestinal bleeding was more common with Sunharbo. The most frequently reported adverse reaction occurring in at least 3% of patients was diarrhea.

The label also says to avoid using the drug with combined P-gp and strong CYP3A4 inducers, not to use it in patients with moderate or severe hepatic impairment, and to withhold it at least 24 hours before elective surgery or invasive procedures. It should also be withheld for at least 24 hours after thrombolysis for acute ischemic stroke. FDA granted the drug Fast Track and Priority Review designations.

The approval is not a broad green light for all stroke prevention settings. FDA specifically said Sunharbo is not approved for stroke prevention in patients with atrial fibrillation, a common heart-rhythm disorder linked to stroke. That limitation is important because asundexian is not a replacement for existing anticoagulants in atrial fibrillation.

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