Janssen Submits New Drug Application to U.S. FDA for Xarelto (rivaroxaban) to Help Prevent and Treat Blood Clots in Pediatric Patients
Application seeks two pediatric indications, including an age-appropriate new weight-based oral suspension formulation to help minimize dosing errors
If approved, XARELTO® will be the first and only oral Factor Xa inhibitor indicated in the U.S. for use in appropriate pediatric patients
RARITAN, NJ, June 23, 2021 – The Janssen Pharmaceutical Companies of Johnson & Johnson announced today it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for the use of XARELTO® (rivaroxaban) in pediatric patients. The NDA seeks two pediatric indications: treatment of venous thromboembolism (VTE, or blood clots) and reduction in the risk of recurrent VTE in patients aged birth to less than 18 years of age after at least five days of initial parenteral anticoagulant treatment; and thromboprophylaxis (prevention of blood clots) in patients aged 2 years and older with congenital heart disease who have undergone the Fontan procedure. If approved, XARELTO® will be the first and only oral Factor Xa inhibitor indicated in the U.S. for use in pediatric patients.
Current guidelines are limited and recommend treating pediatric patients with or at risk for reoccurring blood clots with standard anticoagulant therapy, which often requires painful injections, dietary restrictions and regular laboratory monitoring. There are currently no FDA-approved anticoagulation therapies for pediatric patients with congenital heart disease who have undergone the Fontan procedure, a surgical procedure that redirects blood flow from the lower body to the lungs. The limited guidance for managing these patients leaves physicians to extrapolate adult data to infer pediatric dosing and then regularly monitor their patients.
The application is based on evidence from adequate and well-controlled studies of XARELTO® in adults as well as data from two Phase 3 clinical trials of XARELTO® in pediatric populations: EINSTEIN-Jr, which examined pediatric patients with previously diagnosed VTE, and UNIVERSE, which evaluated pediatric patients who are at risk of VTE after recently undergoing the Fontan procedure.
Part of the industry leading EXPLORER clinical research program, EINSTEIN-Jr is the largest study completed to date evaluating the treatment of pediatric patients with VTE, and UNIVERSE is the first clinical trial to examine a DOAC for the prevention of thromboembolism in congenital heart disease post-Fontan pediatric patients.
For both potential indications, XARELTO® would be dosed based on body weight, either with an oral suspension formulation or tablets. The oral suspension formulation would be administered through a unique color-coded dosing device that was designed to help minimize dosing errors.
Earlier this year, Janssen’s development partner Bayer received approval in Canada, the EU including the UK, Japan and Switzerland for XARELTO® for the treatment of VTE and prevention of VTE recurrence in children and adolescents aged less than 18 years after at least 5 days of initial parenteral anticoagulation treatment.
About EINSTEIN-Jr
EINSTEIN-Jr is a randomized, multicenter, active-controlled, open-label Phase 3 study thatevaluated the use of XARELTO® in 500 children, aged birth to 17 years, with previously diagnosed acute VTE who had started parenteral anticoagulation therapy. Participants were enrolled from November 2014 to September 2018, from 107 sites in 28 countries, and were assigned in a 2:1 ratio to receive either an open-label, body weight-adjusted dose of XARELTO® (tablets or new oral suspension) (n=335) to approximate a 20 mg adult dose or standard anticoagulation therapy (n=165). EINSTEIN-Jr is the largest pediatric study completed to date for the treatment of VTE. It is part of the comprehensive EINSTEIN program, which also included four pivotal Phase 3 studies in adult populations: EINSTEIN-DVT, EINSTEIN-PE, EINSTEIN-EXT and EINSTEIN CHOICE.
About UNIVERSE
UNIVERSE is a randomized, multicenter, open-label, active controlled, two-part, Phase 3 study that examined the use of a novel, oral suspension XARELTO® formulation in children 2-8 years old with single ventricle physiology who had the Fontan procedure within four months before enrollment. From November 2016 to June 2019, a total of 112 participants were enrolled across 36 sites in 10 countries.
UNIVERSE was conducted in two parts. Part A evaluated the single- and multiple-dose PK and PD properties of XARELTO® while Part B evaluated the comparative safety and efficacy of XARELTO® versus aspirin when used for thromboprophylaxis for 12 months.
About EXPLORER
The EXPLORER clinical research program is unmatched by any oral anticoagulant in the Factor Xa inhibitor class in its size, scope and ambition. A collaborative effort between Janssen and Bayer, EXPLORER seeks to generate important clinical evidence on the safety and efficacy of XARELTO® and its potential role in addressing critical unmet medical needs. By the time of its completion, more than 275,000 patients will have participated in the EXPLORER clinical development program, other completed and ongoing clinical trials, investigative registries, and non-interventional studies. Since its inception, the program has built upon extensive evidence reinforcing the benefits of XARELTO® for the millions of patients to whom it has been prescribed since its launch in 2011.
WHAT IS XARELTO® (rivaroxaban)?
XARELTO® is a prescription medicine used to:
· reduce the risk of stroke and blood clots in people who have a medical condition called atrial fibrillation that is not caused by a heart valve problem. With atrial fibrillation, part of the heart does not beat the way it should. This can lead to the formation of blood clots, which can travel to the brain, causing a stroke, or to other parts of the body
· treat blood clots in the veins of your legs (deep vein thrombosis or DVT) or lungs (pulmonary embolism or PE)
· reduce the risk of blood clots happening again in people who continue to be at risk for DVT or PE after receiving treatment for blood clots for at least 6 months
· help prevent a blood clot in the legs and lungs of people who have just had hip or knee replacement surgery
· help prevent blood clots in certain people hospitalized for an acute illness and after discharge, who are at risk of getting blood clots because of the loss of or decreased ability to move around (mobility) and other risks for getting blood clots, and who do not have a high risk of bleeding
XARELTO® is used with low dose aspirin to:
· reduce the risk of serious heart problems, heart attack and stroke in people with coronary artery disease (a condition where the blood supply to the heart is reduced or blocked) or peripheral artery disease (a condition where the blood flow to the legs is reduced)
It is not known if XARELTO® is safe and effective in children.
