Xarelto Demonstrates Strong Efficacy in Phase III EINSTEIN-Jr Trial for Pediatric Venous Thromboembolism, New Indication on the Horizon

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Johnson & Johnson and Bayer announced the latest results from the Phase III EINSTEIN-Jr clinical study of the anticoagulant Xarelto (rivaroxaban) at the 27th International Society on Thrombosis and Haemostasis Congress in 2019: In pediatric patients with venous thromboembolism (VTE), treatment with Xarelto demonstrated a similar risk of recurrent VTE and a similarly low bleeding rate compared with current standard anticoagulant therapy, with efficacy and safety profiles consistent with those previously observed in adult VTE studies. EINSTEIN-Jr is a randomized, open-label study conducted across 107 clinical centers in 28 countries, enrolling a total of 500 pediatric patients (from birth to 17 years of age) who had been previously diagnosed with acute VTE and had already initiated heparin therapy, to evaluate the efficacy and safety of Xarelto relative to standard anticoagulant therapy. In the study, patients were assigned in a 2:1 ratio to receive open-label, weight-adjusted doses of Xarelto (n=335) or standard anticoagulant therapy (n=165). Notably, this study represents the largest pediatric trial ever conducted for the treatment of VTE and is the first study to evaluate a direct oral anticoagulant in this population. The study assessed various tablet strengths of Xarelto as well as a weight-based oral suspension formulation. The primary efficacy endpoint was symptomatic recurrent VTE (fatal or non-fatal), and the primary safety outcome was a composite of major bleeding and clinically relevant non-major bleeding. The results demonstrated that the study met all prespecified endpoints:

• Regarding recurrent VTE, the two treatment groups were similar, with numerically fewer events in the Xarelto group. Recurrent events occurred in 1.2% of patients in the Xarelto group and 3.0% of patients in the standard anticoagulation group; no fatal VTE events occurred in either group.

• Clinically relevant bleeding was also similar, with incidence rates of 3.0% in the Xarelto group and 1.9% in the standard anticoagulation group. No major bleeding events occurred in the Xarelto group, whereas two major bleeding events occurred in the standard anticoagulation group.

• For the composite endpoint of recurrent VTE and major bleeding (net clinical benefit), the incidence was 1.2% in the Xarelto group and 4.2% in the standard anticoagulation group.

• Imaging tests performed at baseline and at the end of the treatment period further confirmed the efficacy of Xarelto in reducing thrombus burden: the rate of complete resolution of initial venous thromboembolism (VTE) volume was 38.5% in the Xarelto group versus 26.1% in the standard anticoagulation group.

Current treatment of venous thromboembolism (VTE) in children typically relies on intravenous anticoagulants, requiring laboratory monitoring and dose adjustments. To date, pediatric anticoagulation regimens have been primarily based on observational data and extrapolation from adult data. The EINSTEIN-Jr study represents a significant advance in the treatment of pediatric VTE. Based on the results of the EINSTEIN-Jr study, Bayer has planned to submit an application to the European Medicines Agency (EMA) to extend the marketing authorization for Xarelto. Xarelto is the most widely used non-vitamin K antagonist oral anticoagulant (NOAC) globally, co-developed by Bayer and Johnson & Johnson. It has currently been approved for eight indications and is marketed in more than 130 countries worldwide. In 2018, global sales of the drug reached $6.149 billion, representing a 9.02% increase compared with 2017. A supplemental new drug application for the prevention of VTE in patients with acute medical illnesses is currently under review by the U.S. Food and Drug Administration (FDA).

Reference Sources:

1、XARELTO® (rivaroxaban) Helps Protect Pediatric Patients from Blood Clots in Late-Breaking Phase 3 EINSTEIN-Jr Study

2、Rivaroxaban demonstrates strong efficacy and safety profile in phase III study in children with thromboembolism