Bayer Submits Application to EMA for Xarelto (Rivaroxaban) in Pediatric Patients Under 18 for Treatment and Secondary Prevention of Venous Thromboembolism (VTE)

November 28, 2019 /BioValleyBIOON/ --Bayer(Bayer) recently announced the submission of an application to the European Medicines Agency (EMA) to expand the indications for the anticoagulant Xarelto (rivaroxaban) to include children under 17 years of age diagnosed with venous thromboembolism (VTE), including cerebral venous sinus thrombosis (CVST). The application covers both the treatment of VTE and the prevention of VTE recurrence.

This application is based on the results of the Phase III clinical study EINSTEIN-Jr. This study is the largest pediatric study ever conducted for the treatment of VTE, and it is also the first study to evaluate a direct oral anticoagulant in children under 17 years of age. In this study, pediatric patients received Xarelto tablets or a newly developed oral suspension. The results showed that Xarelto treatment for VTE in pediatric patients had similar risks of recurrent VTE and similarly low bleeding rates compared to current standard anticoagulant therapy, with efficacy and safety consistent with those observed in previous studies of adult VTE patients.

EINSTEIN-Jr is a randomized, open-label, phase III study that enrolled a total of 500 patients.DiagnosisFor pediatric patients (birth to 17 years of age) with acute VTE who had already initiated heparin therapy. In the study, these pediatric patients were randomized in a 2:1 ratio to receive open-label, weight-adjusted Xarelto (n=335; tablets or suspension) or standard anticoagulant therapy (n=165; unfractionated heparin, low-molecular-weight heparin, or fondaparinux, or switched to a vitamin K antagonist). The treatment duration was 3 months, except for children under 2 years of age with catheter-related VTE, who received 1 month of treatment. Repeat imaging was performed at the end of treatment. The primary efficacy endpoint was symptomatic recurrent VTE (fatal or nonfatal), and the primary safety endpoint was the composite of major bleeding and clinically relevant non-major bleeding.

In early July this year, fromResults of the EINSTEIN-Jr StudyPresented at the 27th Annual Congress of the International Society on Thrombosis and Haemostasis (ISTH 2019), held in Melbourne, Australia.The results showed that the study met all prespecified endpoints: (1) The two groups had similar rates of recurrent VTE events, with a numerically lower rate in the Xarelto treatment group (incidence of recurrent VTE events: 1.2% [n=4] vs. 3.0% [n=5]; HR=0.40, 95% CI: 0.11–1.41). No fatal VTE events occurred in either treatment group. (2) The two groups had similar rates of clinically relevant bleeding, with incidence rates of 3.0% (n=10, all non-major bleeding) in the Xarelto treatment group and 1.9% (n=3, including 2 major bleeding events and 1 non-major bleeding event) in the standard anticoagulation group (HR=1.58, 95% CI: 0.51–6.27). (3) For the composite endpoint of recurrent VTE and major bleeding (net clinical benefit), the incidence was 1.2% in the Xarelto treatment group and 4.2% in the standard anticoagulation group (HR=0.30, 95% CI: 0.08–0.93). (4) Repeat imaging at baseline and at the end of the treatment period demonstrated that Xarelto was superior to standard anticoagulation therapy in reducing thrombus burden (p=0.012): the rate of complete resolution of initial VTE volume was 38.5% in the Xarelto treatment group versus 26.1% in the standard anticoagulation group (overall response ratio: 1.72, 95% CI: 1.12–2.69).

Venous thromboembolism (VTE) affects individuals of all ages. Currently, the treatment of 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 advancement in the treatment of pediatric VTE.

Xarelto is the most widely prescribed non-vitamin K antagonist oral anticoagulant (NOAC) globally, with nine approved therapeutic indications to date; specific indications vary by country. Compared with other NOACs, Xarelto benefits a broad patient population by preventing various venous thromboembolism (VTE) and arterial thromboembolism (ATE) conditions.

This October, Xarelto received U.S.FDAApproved for the prevention of VTE in hospitalized patients with acute medical illnesses who are at risk of thromboembolic complications but not at high risk of bleeding. With the approval of this new indication, Xarelto therapy can be initiated during hospitalization and continued after discharge, with a total recommended duration of 31–39 days.

Xarelto, co-developed by Bayer and Johnson & Johnson, has been approved in more than 130 countries worldwide. Johnson & Johnson is responsible for sales in the U.S. market, while Bayer handles markets outside the United States. In 2018, global sales of Xarelto reached $6.149 billion, representing a 9.02% increase from 2017 ($5.64 billion). (Bioon.com)

Original Source:Bayer submits application to EMA for use of rivaroxaban in children with venous thromboembolism