New Phase 3 data advances pursuit of pediatric indication for Xarelto

Janssen, a pharmaceutical subsidiary of Johnson & Johnson, has announced plans to pursue a pediatric indication for its best-selling blood thinner, Xarelto (rivaroxaban).

The company announced its intent for the broadened indication for the oral anticoagulant following release of the results of the EINSTEIN Jr. Phase 3 study at the 27th International Society on Thrombosis and Haemostasis (ISTH) Congress held July 6 to 10 in Melbourne, Australia.

The randomized, open-label study assessed the efficacy and safety of Xarelto versus standard therapy in 500 children (aged from birth to 17 years) in 28 countries who had been previously diagnosed with acute venous thromboembolism (VTE) and had begun heparin therapy. Nearly 90% of the study participants were children who had conditions in which VTE is a known risk factor such as active cancer, major organ diseases, significant infectious diseases, or major surgery/trauma.

Investigators found that children in the study who received Xarelto had a similar low risk of recurrent VTE and similar rates of bleeding when compared with current standard anticoagulation therapy. 

The EINSTEIN Jr. study met all of its prespecified endpoints, according to Janssen, the main efficacy outcome of which was symptomatic recurrent VTE (fatal or nonfatal), and the chief safety outcome of which was the composite of major and clinically relevant nonmajor bleeding.

The study was sponsored by Janssen and Bayer, which holds rights to overseas marketing of the agent. Janssen’s news release on the trial findings cited Raffini L and colleagues’ 2009 study published in Pediatrics that found that VTE affects approximately 58 per 10,000 hospitalized children in the United States. 

Janssen also revealed that, in addition to Xarelto’s tablet form, the firm has also developed an oral suspension formulation with similar pharmacokinetic properties as the tablet, which would enable “precise dosing and easier administration especially in young children.”

Xarelto is part of a newer class of blood thinners intended to replace the anticoagulant stalwart warfarin, the most commonly prescribed oral anticoagulant in infants and children. Warfarin currently has the sole US Food and Drug Administration pediatric indication, but its use requires frequent monitoring and, in infants and children, is further complicated by diet variations, frequent illnesses, and dynamic and developing hepatic and hemostatic systems.

To date, all competitors holding adult indications for their newer anticoagulant agents either have studies underway toward achieving pediatric indications or have indicated their intentions to pursue them.

Bayer has announced its plan to file for Europe, Middle East, and Africa (EMEA) regulatory approval for the pediatric indication following the study’s conclusion, although it did not release a time frame.