FDA Approves Asundexian for Secondary Stroke Prevention in Adults
Key Clinical Summary
- Asundexian (Sunharbo) was approved for use in combination with antiplatelet therapy to reduce stroke risk following recent non-cardioembolic ischemic stroke or high-risk transient ischemic attack.
- The phase 3 OCEANIC-STROKE trial demonstrated a 26% reduction in ischemic stroke risk with asundexian compared with placebo alongside antiplatelet therapy.
- Major bleeding rates were similar between treatment and control groups, although the US Food and Drug Administration (FDA) identified increased risk in patients over 75 and during early treatment.
The US FDA has approved asundexian (Sunharbo) 50 mg tablets, introducing the first-in-the-world factor XIa inhibitor for use in combination with antiplatelet therapy to reduce the risk of secondary stroke in adults with a recent mild-to-moderate non-cardioembolic ischemic stroke or a high-risk transient ischemic attack (TIA).
“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,” said Ashkan Shoamanesh, MD, co-principal investigator of the OCEANIC-STROKE clinical study that supports the drug’s approval. “I believe asundexian introduces an important new addition to post-stroke care that can be used to help patients reduce the risk of a secondary stroke.”
Asundexian was previously granted Fast Track and Priority Review designations.
Road to Approval
Factor Xla (FXla) is a blood coagulation protein at play in hemostasis and thrombosis, and believed to contribute to pathological clot growth and vessel blockage. FXla has a smaller role in forming the hemostatic plug that seals an injured vessel, according to a news release from Bayer.
Asundexian selectively inhibits FXla, reducing pathological clot formation by unpairing hemostasis from pathological thrombosis. Bayer reports similar rates of major bleeding between asundexian and placebo.
The multicenter, randomized, double-blind, placebo-controlled phase 3 OCEANIC-STROKE randomized 12,327 adults to once-daily asundexian 50 mg or placebo within 72 hours of symptom onset. Both groups received antiplatelet therapy; median treatment lasted 14.2 months.
The primary efficacy endpoint was time to ischemic stroke, and the primary safety endpoint was major bleeding defined by the International Society on Thrombosis and Hemostasis. Asundexian reduced ischemic stroke occurrence by 26% after non-cardioembolic ischemic stroke or high-risk TIA, compared to antiplatelet therapy alone. Similar rates of major bleeding between asundexian and placebo were observed. Bayer reported consistent efficacy across key subgroups, including stroke subtype, severity, and planned antiplatelet regimen.
Side Effects, Contraindications, and Warnings
While overall rates of bleeding were similar between asundexian and placebo, major bleeding increased among patients older than 75 years and during the first 90 days of treatment. Gastrointestinal bleeding was also more frequent with asundexian.
The most frequently reported adverse reaction to asundexian was diarrhea, which occurred in at least 3% of treated patients.
Treatment is not recommended with combined P-glycoprotein and strong cytochrome P450 3A4 inducers, including carbamazepine, because it may reduce asundexian’s efficacy.
Asundexian is not approved for stroke prevention in patients with atrial fibrillation. It is not recommended in patients with in moderate or severe hepatic impairment.
The FDA advises withholding treatment at least 24 hours before elective surgery or invasive procedures and for at least 24 hours after thrombolysis for acute ischemic stroke.
Expert Commentary
“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, MD, MMSc, Director of the Office of Cardiology, Hematology, Endocrinology, and Nephrology in the 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.”
References
