U.S. FDA Approves Xarelto (Rivaroxaban) to Help Prevent Blood Clots in Acutely Ill Medical Patients

XARELTO® provides a new oral option to help prevent venous thromboembolism (VTE) and VTE-related death during hospitalization and post-hospital discharge in acutely ill medical patients at risk for VTE and not at high risk of bleeding

Despite being largely preventable, VTE, or blood clots, remains a significant risk for millions of Americans hospitalized with an acute medical illness

RARITAN, N.J., Oct. 14, 2019 —The Janssen Pharmaceutical Companies of Johnson & Johnson announced today that the U.S. Food and Drug Administration (FDA) has approved XARELTO® (rivaroxaban) for the prevention of venous thromboembolism (VTE), or blood clots, in hospitalized acutely ill medical patients at risk for thromboembolic complications who are not at high risk of bleeding. With the approval of this new indication, XARELTO® can be initiated for these patients during hospitalization and continued after discharge for a total recommended duration of 31 to 39 days. To date, the FDA has granted XARELTO® eight indications – the most of any direct oral anticoagulant (DOAC) – six of which are specifically for the treatment, prevention and reduction in the risk of recurrence of VTE across a wide range of patient populations.

"With this new approval, XARELTO® as an oral-only option now has the potential to change how acutely ill medical patients are managed for the prevention of blood clots, both in the hospital and for an extended period after discharge," said Alex C. Spyropoulos, M.D., Professor of Medicine, The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health at Lenox Hill Hospital, New York, NY.1 "The Phase 3 clinical studies in this high-risk patient group show us that XARELTO® at the 10mg dose is an effective and safe option to help prevent blood clots."

More than seven million Americans are hospitalized each year with an acute medical illness, which is a broad term used to describe serious, yet common, medical conditions.i These patients are at increased risk of blood clots for up to three months after hospital discharge, with 80 percent of events happening within the first six weeks.ii,iii In response to the burden of VTE in hospitalized patients, the Surgeon General issued a Call to Action in 2008 for key stakeholders to build a coordinated plan that could lead to a reduction in VTE across the U.S.iv However, a recent study found that in-hospital VTE rates continue to rise and more work is needed to reduce the burden of VTE especially among those at lower risk.v

Guidelines currently recommend that acutely ill medical patients at risk of VTE receive anticoagulants, typically injectable agents, in the hospital to protect them from blood clots, but advise against routine anticoagulant use after leaving the hospital.vi,vii Research shows that many patients refuse treatment with injectable anticoagulants out of fear, discomfort, anxiety or inconvenience.viii

"Preventing blood clots is a critical priority for physicians treating patients with acute medical illnesses, which is why Janssen is pleased that the FDA approved the use of XARELTO® to address this often fatal, yet preventable condition," said James List, M.D., Ph.D., Global Therapeutic Area Head, Cardiovascular & Metabolism, Janssen Research & Development, LLC. "Rather than facing daily injections with older anticoagulants, patients now have a new oral treatment option that will help prevent blood clots, both in the hospital and after hospital discharge."

About the Phase 3 Clinical Program
More than 20,000 patients with acute medical illnesses were evaluated in the Phase 3 clinical programix,x,which includes the MAGELLAN and MARINER studies. Published in 2013, MAGELLAN evaluated the use of XARELTO® in preventing VTE in hospitalized patients with an acute medical illness and restricted mobility, starting with their hospital stay and continuing through post-hospital discharge. The study met its two co-primary efficacy endpoints, with XARELTO® demonstrating non-inferiority to enoxaparin, a low-molecular-weight heparin (LMWH), in short-term use (10 ± 4 days) and superiority in long-term use (35 ± 4 days) compared to short-term use of enoxaparin followed by placebo. The combined rates of major and non-major clinically relevant bleeding were higher in the XARELTO® group.

An important post-hoc analysis from MAGELLAN found that, by applying five additional exclusionary criteria to remove patients at high risk for bleeding due to active gastroduodenal ulcer, recent bleeding, active cancer, history of severe bronchiectasis or pulmonary cavitation, or dual antiplatelet therapy at baseline, researchers established a favorable benefit-risk profile for VTE prevention with XARELTO®.

Additionally, building on the foundation from MAGELLAN, the Phase 3 MARINER trial was conducted in a similar population of acutely ill medical patients. Published in 2018, MARINER evaluated XARELTO® for the prevention of VTE and VTE-related death following hospital discharge compared to placebo. While XARELTO® did not reduce the composite endpoint of VTE and VTE-related death, it did significantly reduce symptomatic VTE with consistent and favorable safety, reinforcing the positive benefit-risk profile of XARELTO®.

MAGELLAN and MARINER are part of the EXPLORER clinical research program for XARELTO®. As a collaborative effort between Janssen and its development partner Bayer, EXPLORER has generated important clinical evidence on the safety and efficacy of XARELTO®. Many studies in the program are designed to seek additional indications or expand the label for XARELTO® to benefit more patients in need of therapies for their cardiovascular disease. By the time of its completion, more than 275,000 patients will have participated in the EXPLORER program, other completed and ongoing clinical trials, investigative registries and non-interventional studies.

1 Dr. Alex C Spyropoulos served as a Member of the Steering Committee of the MAGELLAN trial and was compensated for his work.

i Kahn SR et al. Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis. 9th ed. American College of Chest Physicians Evidence-Based Clinical Practice Guideline. Chest 2012;141(suppl 2):e195S–e226S.

ii Spyropoulos AC et al. IMPROVE Investigators. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest 2011;140:706–14.

iii Hull RD et al. Venous thromboembolism in elderly high-risk medical patients: time course of events and influence of risk factors. Clin Appl Thromb Hemost 2013;19:357–62.

iv Office of the Surgeon General, National Heart, Lung and Blood Institute. Publications and reports of The Surgeon General. The Surgeon General's Call to Action to Prevent Deep Vein Thrombosis and Pulmonary Embolism. Rockville, MD: Office of the Surgeon General (US); 2008.

v Mehta KD et al. Trends of Inpatient Venous Thromboembolism in United States Before and After the Surgeon General's Call to Action. Am J Cardiol. 2019;124:960−965.

vi Kahn SR et al. Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis. 9th ed. American College of Chest Physicians Evidence-Based Clinical Practice Guideline. Chest. 2012;141(suppl 2):e195S–e226S.

vii Schünemann et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients. Blood Advances. 2018;2:3198-3225.

viii Fanikos J et al. Adherence to Pharmacological Thromboprophylaxis Orders in Hospitalized Patients. Am J Med. 2010;123:536-541.

ix Cohen A et al. Rivaroxaban for Thromboprophylaxis in Acutely Ill Medical Patients. N Engl J Med. 2013;368:513-523.

x Spyropoulos A et al. Rivaroxaban for Thromboprophylaxis after Hospitalization for Medical Illness. N Engl J Med. 2018;379:1118-1127.