- Source : Press Release
- Date : 2021-01-22
- Event type : Approved
- Companies : Bayer AG
Japan Approves Rivaroxaban (XareltoTM) to Treat Children with Venous Thromboembolism (VTE) and to Prevent Recurrence
Berlin, January 22, 2021 – The Ministry of Health, Labor and Welfare in Japan has approved the use of the oral Factor Xa inhibitor rivaroxaban (Xarelto™) to treat VTE and prevent VTE recurrence in children, including catheter related thrombosis, cerebral vein and sinus thrombosis. The use of an oral suspension was also approved.
Rivaroxaban, already indicated for the treatment of VTE and the prevention of recurrence in adult patients, is the first oral Factor Xa Inhibitor approved for pediatric treatment and secondary prevention of VTE.
“The rivaroxaban regimen represents an advantageous alternative treatment for children with VTE – with a safety and efficacy profile based on data from the most extensive and comprehensive clinical study program completed to date in pediatric thromboembolism,” said Dr. Michael Devoy, Head of Medical Affairs & Pharmacovigilance of Bayer AG's Pharmaceutical Division and Chief Medical Officer at Bayer.
The approval is based on data from a comprehensive clinical program, including the phase III EINSTEIN-Jr. study – the largest program completed to date investigating the treatment of pediatric patients with VTE.(1) Pediatric VTE typically occurs in children with life-threatening illnesses, and due to frequent hospitalizations often for extended periods of time, these patients are at an increased risk of VTE. Moreover, current pediatric treatment of VTE is based mainly on observational data and extrapolation from VTE studies in adults using injectable heparins and/or Vitamin K antagonists.
During the phase III EINSTEIN-Jr. study, following completion of least 5 days of anticoagulation with heparin, children in the rivaroxaban-arm received rivaroxaban, body weight adjusted equivalent to the 20 mg once daily adult dose used to treat deep vein thrombosis (DVT)/ pulmonary embolism (PE). These dosages were administered as tablets or as granules for oral suspension. This study demonstrated a numerically lower incidence of recurrent VTE in children treated with rivaroxaban, compared with standard of care (injections of heparin alone or switched to a vitamin K antagonist such as warfarin). With no difference seen in the primary safety endpoint of major or clinically relevant non major bleeding, the absolute and relative safety and efficacy results seen in the EINSTEIN-Jr. study are consistent with those from previous rivaroxaban studies in adults.(1)
About Pediatric Venous Thromboembolism (VTE)
Pediatric VTE includes cerebral vein and sinus thrombosis (a blood clot in the brain), central venous catheter related thrombosis, pulmonary embolism (a blood clot that travels to the lung), and deep vein thrombosis (a blood clot in a deep vein).
Due to improved treatment and survival rates amongst children with life-threatening or chronic medical conditions, as well as increased awareness of venous thromboembolism (VTE) among pediatricians, VTE is being identified more often in hospitalized children.(1) The most common risk factor for VTE in children is venous catheterization.
Currently, recommended treatment options for VTE include unfractionated heparin, low molecular weight heparin, and fondaparinux with or without a vitamin K antagonist therapy. Until now, there was no treatment option in Japan for children with VTE that does not require prolonged subcutaneous or intravenous injections or regular coagulation monitoring, which can be a substantial burden for small children – especially babies – and also for their parents and caregivers. To address this, Bayer has developed granules for oral suspension of rivaroxaban that does not require injections or regular monitoring, and which enables precise dosing and easier administration of treatment for children with VTE.
The dose of the oral suspension or the tablets is based on the child’s weight. The weight related dose of the oral suspension has been developed to be equivalent to the adult standard dose of 20 mg (15 mg in Japan) once daily. Children at least 30 kg or more can be treated with either the oral suspension or appropriate rivaroxaban tablets.(1)
About the EINSTEIN-Jr. Study
The randomized, open-label phase III EINSTEIN-Jr. study included 500 children aged from birth to below 18 years with documented acute VTE who had started heparin therapy for at least 5 days. Children were assigned, in a 2:1 ratio, to receive body weight-adjusted rivaroxaban (tablets or oral suspension) in a 20 mg-equivalent dose, or standard of care with (low molecular weight) heparin, fondaparinux or vitamin K antagonist therapy. The main treatment period was 3 months, but in children younger than 2 years with catheter related VTE it was 1 month. Repeat imaging was carried out at the end of the treatment period. Importantly, the results were also interpreted in the context of previous studies evaluating rivaroxaban in adults with VTE.
Recurrent VTE occurred in 4 of the 335 (1.2%) children assigned to rivaroxaban and in 5 of the 165 (3.0%) children assigned to standard of care (hazard ratio 0.40; 95% confidence intervals, 0.11 to 1.41). Repeat imaging showed an improved effect of rivaroxaban on thrombotic burden as compared with standard of care (P=0.012). Major or clinically relevant non-major bleeding occurred in 10 children (3.0%; all non-major bleeds) with rivaroxaban and in 3 children (1.9%; two major and 1 non-major bleeds) with standard of care.
About Rivaroxaban (Xarelto™)
Rivaroxaban is the most broadly indicated non-vitamin K antagonist oral anticoagulant (NOAC) worldwide and is marketed under the brand name Xarelto. Xarelto is approved for more venous and arterial thromboembolic (VAT) conditions than any other NOAC:
- The prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation (AF) with one or more risk factors
- The treatment of pulmonary embolism (PE) in adults
- The treatment of deep vein thrombosis (DVT) in adults
- The prevention of recurrent PE and/or DVT in adults
- The prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip replacement surgery
- The prevention of VTE in adult patients undergoing elective knee replacement surgery
- The prevention of atherothrombotic events after an Acute Coronary Syndrome in adult patients with elevated cardiac biomarkers when co-administered with acetylsalicylic acid (ASA) alone or with ASA plus clopidogrel or ticlopidine
- The prevention of atherothrombotic events in adult patients with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) at high risk for ischaemic events, when co-administered with acetylsalicylic acid (ASA)
Rivaroxaban was discovered by Bayer, and is being jointly developed with Janssen Research & Development, LLC. Xarelto is marketed outside the U.S. by Bayer and in the U.S. by Janssen Pharmaceuticals, Inc. (Janssen Research & Development, LLC and Janssen Pharmaceuticals, Inc. are part of the Janssen Pharmaceutical Companies of Johnson & Johnson).
Anticoagulant medicines are therapies used to prevent or treat serious illnesses and potentially life-threatening conditions. Before initiating treatment with anticoagulant medicines, physicians should carefully assess the benefit and risk for the individual patient.
Responsible use of Xarelto is a very high priority for Bayer, and the company has developed a Prescribers Guide for physicians and a Xarelto Patient Card for patients to support best practice.
To learn more about thrombosis, please visit www.thrombosisadviser.com and www.vascularadviser.com
To learn more about Xarelto, please visit www.xarelto.com
Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to benefit people by supporting efforts to overcome the major challenges presented by a growing and aging global population. At the same time, the Group aims to increase its earning power and create value through innovation and growth. Bayer is committed to the principles of sustainable development, and the Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2019, the Group employed around 104,000 people and had sales of 43.5 billion euros. Capital expenditures amounted to 2.9 billion euros, R&D expenses to 5.3 billion euros. For more information, go to www.bayer.com.
(1) Male, C, et al, ‘Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial’, The Lancet Haematology, 7.1 (2019), pp.18-27.
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