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Janssen Submits Application to U.S. FDA for New Indication to Expand Use of Xarelto (rivaroxaban) in Patients with Peripheral Artery Disease

Press Release

Janssen Submits Application to U.S. FDA for New Indication to Expand Use of Xarelto (rivaroxaban) in Patients with Peripheral Artery Disease


Application seeks approval of XARELTO® plus aspirin to reduce the risk of major thrombotic vascular events in patients after lower-extremity revascularization due to symptomatic peripheral artery disease (PAD)

XARELTO® is currently approved to reduce the risk of major cardiovascular events, like heart attack and stroke, in people with chronic PAD

An estimated 20 million Americans are living with PAD, a disease often underdiagnosed and undertreated

RARITAN, N.J., Oct. 26, 2020 -- The Janssen Pharmaceutical Companies of Johnson & Johnson announced today it has submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for a new indication to expand the use of XARELTO® (rivaroxaban) in patients with peripheral artery disease (PAD). If approved, this new indication for the XARELTO® vascular dose (2.5 mg twice daily plus aspirin 75-100 mg once daily) would include reducing the risk of major thrombotic vascular events such as heart attack, stroke and amputation in patients after recent lower-extremity revascularization, a common procedure in which blood flow is restored to the legs and feet due to symptomatic PAD. The application is based on data from the VOYAGER PAD study, which showed XARELTO® (2.5 mg twice daily) plus aspirin (100 mg once daily) was superior to aspirin alone in reducing the risk of major cardiovascular (CV) and limb events, with similar rates of Thrombolysis In Myocardial Infarction (TIMI) major bleeding.

"Various antithrombotic regimens have been evaluated for short- and long-term prevention of major vascular events in patients with PAD, but only rivaroxaban in combination with aspirin has demonstrated a significant benefit over aspirin alone," said James List, M.D., Ph.D., Global Therapeutic Area Head, Cardiovascular & Metabolism, Janssen Research & Development, LLC. "Data from the VOYAGER PAD trial were the first in 20 years to show clinical benefit with an antithrombotic therapy in the symptomatic PAD population after lower-extremity revascularization, which speaks to the need for a new treatment in this space. We look forward to discussing these data with the FDA."

Janssen and its development partner Bayer have conducted two major Phase 3 trials, VOYAGER PAD and COMPASS, that evaluated the use of dual antithrombotic pathway inhibition with XARELTO® plus aspirin in patients with PAD. XARELTO®, in combination with aspirin, was approved by the FDA in 2018 to reduce the risk of major CV events in patients with chronic PAD and coronary artery disease (CAD) – the only direct oral anticoagulant (DOAC) approved for use in these populations.

PAD is a serious underlying health crisis that impacts an estimated 20 million Americans, with only 8.5 million diagnosed.i,ii PAD also increases the risk for major CV events and is the leading cause of amputation,iii which can double a patient's risk of death.iv 

The Phase 3 VOYAGER PAD study included 6,564 patients from 542 sites across 34 countries worldwide. Patients were randomized in a 1:1 ratio and received either XARELTO® (2.5 mg twice daily) plus aspirin (100 mg once daily) (n=3,286) or aspirin alone (100 mg once daily) (n=3,278). Patients were stratified by revascularization procedure type (endovascular vs. surgical) and use of clopidogrel, which was limited and administered based on the treating physician's discretion. Patients were followed for a median duration of 28 months. 

The primary efficacy endpoint was a composite of major adverse limb and CV events, including acute limb ischemia, major amputation for vascular causes, heart attack (myocardial infarction), ischemic stroke, or death from CV causes. The principal safety endpoint was major bleeding according to the TIMI classification. 

Eligible patients were at least 50 years old and had documented symptomatic lower-extremity PAD. Patients were eligible after a successful revascularization for symptomatic PAD within the last 10 days. Approximately two-thirds were treated with an endovascular procedure (65%) and one-third treated surgically (35%). Patients were excluded if they were clinically unstable, at heightened bleeding risk, or needed prohibited concomitant medications, including long-term clopidogrel. The median age was 67 years and 26% were women. Common risk factors for PAD included diabetes, an estimated glomerular filtration rate less than 60 mL/min/1.73 m2 (indicating mild-to-moderate kidney disease) and current smokers.

Please read full Prescribing Information, including Boxed Warnings, and Medication Guide for XARELTO®.

Trademarks are those of their respective owners. Janssen and Bayer together are developing rivaroxaban.

About Janssen Cardiovascular & Metabolism 
In Cardiovascular & Metabolism (CVM), we take on the most pervasive diseases that burden hundreds of millions of people and healthcare systems around the world. As part of this long-standing commitment and propelled by our successes in treating type 2 diabetes and thrombosis, we advance highly differentiated therapies that prevent and treat life-threatening cardiovascular, metabolic and retinal diseases. Uncovering new therapies that can improve the quality of life for this large segment of the population is an important endeavor – one which Janssen CVM will continue to lead in the years to come. Our mission is global, local and personal. Together, we can reshape the future of cardiovascular, metabolic and retinal disease prevention and treatment. Please visit

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 Follow us at and Janssen Research & Development, LLC, is one of the Janssen Pharmaceutical Companies of Johnson & Johnson.

i Racial Disparities in Vascular Care. (n.d.). Retrieved October 2, 2020, from 
ii Centers for Disease Control and Prevention. Peripheral Arterial Disease Fact Sheet/Data & Statistics. Retrieved March 20, 2020 from:
iii Norgren L, Hiatt WR, Dormandy JA, Hirsch AT, et al. The next 10 years in the management of peripheral artery disease: perspectives from the 'PAD 2009' Conference. Eur Vasc Endovasc Surg. 2010;40(3):375-380.
iv Jones WS, Patel MR, Dai D, et al. High mortality risks after major lower extremity amputation in Medicare patients with peripheral artery disease. Am Heart J. 2013;165(5):809-815.

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