The National Institutes of Health (NIH) halted a treatment arm of Bayer and Johnson & Johnson’s Xarelto (rivaroxaban) in a phase 3 stroke prevention trial after an independent committee flagged safety concerns and a lack of efficacy.
The decision, announced Tuesday, follows a recommendation from a data safety and monitoring board, which found that the combination of a low dose of Xarelto and aspirin was unlikely to help prevent recurrent strokes compared with the standard of care in the phase 3 Captiva study.
The board identified “an increase in safety events and evidence of futility,” the NIH—which funded the study—said in a Feb. 10 release. The release didn’t identify the specific safety signals.
Xarelto’s current FDA label includes a boxed warning about increased risks of blood clots upon premature discontinuation. Anticoagulants like Xarelto may also cause serious bleeding.
In the study, Xarelto was evaluated at a dose of 2.5 mg twice daily and was compared against clopidogrel (Plavix), both on top of aspirin. The trial has a second experimental arm evaluating AstraZeneca’s Brilinta and aspirin.
The goal of the trial is to see whether either of the two blood-thinning regimens would be better than the current treatment to prevent another stroke in patients with narrowed brain arteries, which is one of the most common causes of stroke worldwide. The study is evaluating up to 1,683 participants, who are randomized 1:1:1 to receive one year of treatment with one of those three aspirin combo regimens.
In a statement to Fierce Pharma, a J&J spokesperson said the discontinuation is “not related to any approved indications for Xarelto.”
First approved by the FDA in 2011, Xarelto’s U.S. label includes its uses at 15 mg or 20 mg once daily to reduce the risk of stroke and systemic embolism in nonvalvular atrial fibrillation. The regimen utilized in the Captiva study—2.5 mg Xarelto twice daily, in combination with aspirin—is approved by the FDA to reduce the risk of certain cardiovascular events, including stroke, in people with chronic coronary artery disease or peripheral artery disease.
Generic versions of Xarelto are already available in the U.S. after Lupin and Taro Pharmaceuticals gained the first FDA approvals for their 2.5 mg copycats last year and launched immediately. Last year, Xarelto’s U.S. sales to J&J reached $2.6 billion, marking 11% growth compared with 2024. That said, the drug's fourth-quarter sales were roughly flat year over year.
As Xarelto ages, J&J is shifting its focus to Bristol Myers Squibb-partnered factor XIa inhibitor milvexian, which is expected to report phase 3 results in secondary stroke prevention in the second half of 2026. J&J has predicted the new antithrombotic agent could reach more than $5 billion in peak annual sales.
“What we’re really looking to show there is clear superiority in terms of safety and bleeding risk,” Jennifer Taubert, who leads J&J’s pharmaceuticals business, said about milvexian during the company’s fourth-quarter earnings call in January.
“We know from all of our experience in the market with Xarelto that there are a lot of patients that are not treated or are undertreated because of fear of safety risk,” she continued. “So we think there’s extraordinary need for a highly efficacious and highly safe with low bleeding risk product in the market.”
Editor's Note: The story was updated at 7:45 p.m. U.S. ET with a statement from J&J.