EINSTEIN-Jr is the largest pediatric trial conducted for the treatment of venous thromboembolism (VTE) and the first to evaluate a direct oral anticoagulant in this population
| RARITAN, N.J., July 8, 2019 /PRNewswire/ -- The Janssen Pharmaceutical Companies of Johnson & Johnson announced today new results from the Phase 3 EINSTEIN-Jr study, showing pediatric patients (aged birth to 17 years) treated with XARELTO® (rivaroxaban) had a similar low risk of recurrent venous thromboembolism (VTE) – or blood clots – and similar rates of bleeding when compared to current standard anticoagulation therapy. These results from the largest pediatric study ever conducted for the treatment of VTE also show that the efficacy and safety profile of XARELTO® in a pediatric population with VTE is comparable to what has been observed in previous studies of adults with VTE. The full findings were presented during a late-breaking session at the 27th Congress of the International Society on Thrombosis and Haemostasis (ISTH) in Melbourne, Australia.
While VTE more commonly occurs in adults, it affects approximately 58 per 10,000 hospitalized children in the United Statesi. There are very limited treatment options for these young patients, and no direct oral anticoagulant is currently approved for use in this setting. Current treatment is mainly based on observational data in this group and extrapolation of data obtained in adults, even though the pathophysiology and anatomic distribution (where it occurs in the body) of VTE, along with anticoagulant responses, differ between children and adults. Until EINSTEIN-Jr, only one small randomized trial had been published evaluating the use of standard anticoagulants in pediatric patients with VTE.ii Current guidelines recommend that young patients with VTE be treated with standard anticoagulation therapy. For these patients, physicians manipulate adult dosage forms of these older anticoagulants, many of which require injections and regular laboratory monitoring. “This trial examined for the first time whether a direct oral anticoagulant could alleviate the burden of blood clots in young patients, which would allow them to focus on recovering from their other health challenges,” said Christoph Male, M.D., Department of Pediatrics, Medical University of Vienna, Vienna, Austria.1 “The EINSTEIN-Jr study with rivaroxaban represents a significant advance for pediatric VTE treatment.” Click to Tweet: Results from the largest pediatric study ever conducted for the treatment of #bloodclots represent a significant advance for pediatric #VTE treatment https://ctt.ec/97800+ The main efficacy outcome of EINSTEIN-Jr was symptomatic recurrent VTE (fatal or non-fatal), and the principal safety outcome was the composite of major and clinically relevant non-major bleeding. The study met all of its prespecified endpoints. The following observations were made:
The efficacy of XARELTO® was further demonstrated by reduction in clot burden on imaging tests that were conducted on patients both at baseline and at the end of the treatment period. Complete resolution of the initial VTE mass occurred in 38.5 percent of the XARELTO® group compared to 26.1 percent of the standard anticoagulation group (Overall Response: 1.72; 95% CI, 1.12 to 2.69). “VTE affects people of all ages, which is why we are committed to advancing new research and uncovering ways for XARELTO® to help people in need,” said James List, M.D., Ph.D., Global Therapeutic Area Head, Cardiovascular & Metabolism, Janssen Research & Development, LLC. “The EINSTEIN-Jr. results offer important insights on the efficacy and safety of XARELTO® in managing blood clots in our youngest patients.” Study Background Participants were enrolled from November 2014 to September 2018 and were assigned in a 2:1 ratio to receive either an open-label, bodyweight-adjusted dose of XARELTO® (n=335) or standard anticoagulation therapy (n=165). Various tablet strengths and weight-based oral liquid suspension doses of XARELTO® were tested. Standard anticoagulants were given at therapeutic doses, according to international guidelines, and included unfractionated heparin, low-molecular-weight heparin (LMWH) or fondaparinux; following completion of five to nine days of standard anticoagulation, participants continued with heparin treatment or were switched to a vitamin K antagonist (VKA) at the discretion of the treating physician. Approximately 90 percent of enrolled patients had conditions in which VTE is a known risk factor. Major surgery/trauma, major infectious diseases, major organ diseases and active cancer were among the most common conditions. For the index event, VTE was symptomatic in approximately 80 percent of participants and asymptomatic in approximately 20 percent. Of those enrolled, 23.4 percent had cerebral vein or sinus VTE, 25.4 percent had catheter-related VTE and 51.2 percent had other non-catheter-related VTE as their index event. Participants were ineligible if they had active bleeding or were at high risk of bleeding contraindicating anticoagulant therapy, had a low platelet count, hepatic disease associated with a coagulopathy (bleeding disorder), severe renal impairment, or a life expectancy of less than three months. The main treatment period was three months (or one month in children younger than two years with catheter-related VTE). Prior to EINSTEIN-Jr, Phase 1 and 2 studies were conducted to establish bodyweight-adjusted dose regimens of XARELTO® for children aged birth to 17 years that matched the exposure range in adults younger than 45 years treated with XARELTO® 20-mg once daily. In addition to a tablet form of XARELTO®, an oral suspension formulation of XARELTO® was developed, with similar pharmacokinetic properties as the tablet formulation, which enabled precise dosing and easier administration especially in young children. More on the Pediatric Program with XARELTO® In adults, XARELTO® already has five approved VTE indications, the most of any direct oral anticoagulant, including the treatment of deep vein thrombosis (DVT), treatment of pulmonary embolism (PE), reduction of the risk of recurrent DVT and PE, and primary prevention of DVT which may lead to PE in people who have just had hip or knee replacement surgery. In October 2017, the FDA approved a new dose regimen of 10-mg XARELTO® once-daily for reducing the continued risk for recurrent VTE after completion of at least six months of initial therapy. The FDA is currently reviewing a supplemental New Drug Application (sNDA) for XARELTO® for the prevention of VTE in medically ill patients. About the EINSTEIN Clinical Trial Program About EXPLORER WHAT IS XARELTO®? XARELTO® is a prescription medicine used to:
XARELTO® is also used with low dose aspirin to:
It is not known if XARELTO® is safe and effective in children. IMPORTANT SAFETY INFORMATION WHAT IS THE MOST IMPORTANT INFORMATION I SHOULD KNOW ABOUT XARELTO®? XARELTO® may cause serious side effects, including:
Tell your doctor if you take any of these medicines. Ask your doctor or pharmacist if you are not sure if your medicine is one listed above. Call your doctor or get medical help right away if you develop any of these signs or symptoms of bleeding:
If you take XARELTO® and receive spinal anesthesia or have a spinal puncture, your doctor should watch you closely for symptoms of spinal or epidural blood clots. Tell your doctor right away if you have back pain, tingling, numbness, muscle weakness (especially in your legs and feet), or loss of control of the bowels or bladder (incontinence).
Do not take XARELTO® if you:
Before taking XARELTO®, tell your doctor about all your medical conditions, including if you:
Tell all of your doctors and dentists that you are taking XARELTO®. They should talk to the doctor who prescribed XARELTO® for you before you have any surgery, medical or dental procedure. Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Some of your other medicines may affect the way XARELTO® works, causing side effects. Certain medicines may increase your risk of bleeding. See “What is the most important information I should know about XARELTO®?” HOW SHOULD I TAKE XARELTO®?
WHAT ARE THE POSSIBLE SIDE EFFECTS OF XARELTO®?
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Janssen Pharmaceuticals, Inc., at 1-800-JANSSEN (1-800-526-7736). Please click here for full Prescribing Information, including Boxed Warnings, and Medication Guide. Trademarks are those of their respective owners. Janssen and Bayer together are developing rivaroxaban. For more information about XARELTO®, visit www.xarelto.com. About the Janssen Pharmaceutical Companies of Johnson & Johnson At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension. Learn more at www.janssen.com. Follow us at www.twitter.com/JanssenGlobal. Janssen Research & Development, LLC is one of the Janssen Pharmaceutical Companies of Johnson & Johnson. Cautions Concerning Forward-Looking Statements This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding XARELTO® (rivaroxaban). The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, any of the other Janssen Pharmaceutical Companies and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended December 30, 2018, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in the company’s most recently filed Quarterly Report on Form 10-Q, and the company’s subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. Neither the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. Media contacts: Andrew Wheatley Investor contacts: Lesley Fishman 1 Dr. Christoph Male was compensated for his work on the EINSTEIN-Jr study. i Raffini L et al. Dramatic increase in venous thromboembolism in children’s hospitals in the United States from 2001 to 2007. Pediatrics. 2009;124:1001–1008.
SOURCE Janssen Pharmaceutical Companies of Johnson & Johnson |
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