FDA approves Sunharbo as first factor XIa inhibitor after stroke

The U.S. Food and Drug Administration has approved Sunharbo (asundexian) 50 mg tablets from Bayer HealthCare Pharmaceuticals as the first factor XIa inhibitor for lowering stroke risk in adults with a recent mild-to-moderate ischemic stroke that was not cardioembolic, or a high-risk transient ischemic attack.

The approval is for use together with antiplatelet therapy, the FDA said.

The approval is supported by OCEANIC-STROKE, a phase 3 study that was conducted at multiple centers and used a randomized, double-blind, placebo-controlled design. It enrolled 12,327 adults. Participants had a recent ischemic stroke that was not cardioembolic and was mild-to-moderate, with an NIH Stroke Scale score of 15 or lower, or a high-risk transient ischemic attack. They were randomly assigned within 72 hours of symptom onset to once-daily Sunharbo 50 mg or placebo, and all also received antiplatelet therapy. Over a median treatment duration of 14.2 months, the risk of ischemic stroke was 26% lower with Sunharbo than with placebo.

STAT reported that in the trial, 8.4% of placebo-treated participants had a secondary stroke, while 6.2% of those on Sunharbo did, a relative reduction of 26%. STAT also said that treating 53 patients for a year would prevent one recurrent stroke.

According to STAT, many blood thinners are not used after these strokes because of the risk of bleeding. Sunharbo blocks a protein called XIa, a mechanism intended to stop harmful clots without increasing bleeding, and it is the first drug in this class.

Major bleeding rates overall were comparable between groups, according to the FDA, but Sunharbo was linked to more major bleeding in those over 75 and in the initial 90 days of therapy. Gastrointestinal bleeding occurred more often with Sunharbo than placebo. The most common adverse reaction, reported in 3% or more of patients on Sunharbo, was diarrhea.

The agency advises against using Sunharbo with drugs that are both P-glycoprotein inducers and strong CYP3A4 inducers, such as carbamazepine, because these drugs may reduce its effectiveness. It is also not recommended for patients with moderate or severe liver impairment. The FDA says Sunharbo should be paused for at least one day before elective surgery or an invasive procedure, and for at least one day after thrombolysis for acute ischemic stroke. The drug is not approved for stroke prevention in atrial fibrillation.

In the FDA's announcement, Hylton V. Joffe, who directs the office that covers cardiology, hematology, endocrinology, and nephrology, said the approval "represents a meaningful advance for patients and health care providers seeking a new option for secondary stroke prevention."

Sunharbo received Fast Track and Priority Review designations. Bayer HealthCare Pharmaceuticals, based in Whippany, New Jersey, holds the approval.