The US Food and Drug Administration (FDA) this week approved Sunharbo (asundexian) 50mg tablets—the first Factor XIa inhibitor approved in the USA for use in combination with antiplatelet therapy to reduce the risk of stroke in adult patients following a recent mild-to-moderate non-cardioembolic ischaemic stroke or a high-risk transient ischaemic attack (TIA). The approval was granted to Bayer HealthCare Pharmaceuticals, the company that develops the drug.
“Stroke is a leading cause of disability and death in the USA, and survivors are at risk of having another stroke,” said Hylton V Joffe, director of the Office of Cardiology, Hematology, Endocrinology and Nephrology in the US FDA’s Center for Drug Evaluation and Research. “[This] approval represents a meaningful advance for patients and healthcare providers seeking a new option for secondary stroke prevention.”
The effectiveness of Sunharbo was demonstrated in the OCEANIC-STROKE study, a multicentre, randomised, double-blind, placebo-controlled Phase 3 study that enrolled 12,327 adults. Participants had a recent non-cardioembolic ischaemic stroke—with a National Institutes of Health stroke scale (NIHSS) score ≤15—or high-risk TIA, and were randomly assigned to Sunharbo or placebo within 72 hours of symptom onset. Both groups also received antiplatelet therapy.
Sunharbo 50mg—taken once daily—significantly reduced the risk of ischaemic stroke by 26% compared to placebo over a median treatment period of 14.2 months.
Additionally, the overall rate of major bleeding was similar between the Sunharbo and placebo groups, but was increased with Sunharbo in patients older than 75 years and during the first 90 days of treatment. Gastrointestinal bleeding occurred more commonly with Sunharbo compared to placebo, and the most frequently reported adverse reaction—occurring in 3% or greater of Sunharbo-treated patients—was diarrhoea.
“For those who survive a stroke, the risk of another potentially devastating event is highest in the days and weeks after the initial event, and that risk persists over time,” commented Ashkan Shoamanesh (McMaster University, Hamilton, Canada), co-principal investigator of the OCEANIC-STROKE study. “I believe Sunharbo introduces an important new addition to post-stroke care that can be used to help patients reduce the risk of a secondary stroke.”
In a news release, the US FDA notes that concomitant use of this drug with medicines that are combined P-glycoprotein (P-gp) and strong CYP3A4 inducers, such as carbamazepine, is not recommended, because these medicines may decrease Sunharbo’s effectiveness. The regulator also states that Sunharbo is not recommended in patients with moderate or severe hepatic impairment. Sunharbo, the US FDA adds, should be withheld at least 24 hours before elective surgery or invasive procedures, and for at least 24 hours after thrombolysis for acute ischaemic stroke.
Sunharbo is not approved for stroke prevention in patients with atrial fibrillation.
In its own press release, Bayer claims that this marks the first US approval of a Factor XIa inhibitor, thus representing a “new approach” to reducing the risk of ischaemic stroke. The company anticipates that Sunharbo will begin shipping in mid-to-late November, and is expected to become available for hospitals and pharmacies to order across the USA shortly thereafter.
“For decades, Bayer has worked to advance care in cardiovascular and cerebrovascular diseases,” added Nelson Ambrogio, president of Bayer US Pharmaceuticals. “[This] approval offers stroke patients a novel treatment option to reduce their risk of stroke, building on our company’s legacy to develop first-in-class products that address significant health challenges. We are proud to bring the first approved Factor XIa inhibitor to market in the USA for secondary stroke prevention.”
