FDA Approves Expanded Peripheral Artery Disease (PAD) Indication for XARELTO (rivaroxaban) Plus Aspirin to Include Patients After Lower-Extremity…

RARITAN, N.J., Aug. 24, 2021 /PRNewswire/ -- The Janssen Pharmaceutical Companies of Johnson & Johnson today announced that the U.S. Food and Drug Administration (FDA) has approved an expanded peripheral artery disease (PAD) indication for the XARELTO (rivaroxaban) vascular dose (2.5 mg twice daily plus aspirin 100 mg once daily) to include patients following recent lower-extremity revascularization (LER) due to symptomatic PAD. The approval is based on data from the Phase 3 VOYAGER PAD study. With this approval, XARELTO is the first and only therapy indicated to help reduce the risks of major cardiovascular (CV) events in patients with coronary artery disease (CAD) and major thrombotic vascular events, such as myocardial infarction, ischemic stroke, acute limb ischemia, and major amputation of a vascular etiology,in patients with PAD, including patients who have recently undergone LER due to symptomatic PAD.

CLICK TO TWEET: #BREAKINGNEWS: @US_FDA approves expanded #PeripheralArteryDisease #PAD indication for @JanssenUS treatment, evolving current standard of care for #PAD patients & how long-term prevention of persistent #bloodclot related events are managed. Learn more: bit.ly/33sm1yt

"For more than 20 years, many physicians have used dual antiplatelet therapy after lower extremity revascularization due to symptomatic PAD with limited data to support efficacy and safety in this setting. Now, the VOYAGER PAD and COMPASS clinical studies have demonstrated the utility of dual pathway inhibition in targeting both platelets and thrombin in patients with PAD. These data provide a new mechanism of treatment using an evidence-based strategy for this vulnerable population," said Marc P. Bonaca*, M.D., M.P.H., Department of Medicine, Division of Cardiovascular Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado. "This FDA approval of rivaroxaban plus aspirin is a major advancement for PAD management and sets the stage to evolve the current standard of care for patients with PAD."

PAD is a common chronic circulatory condition that causes blood vessels to narrow, thereby reducing blood flow to the limbs, most often the legs.3 It is a disease which often goes undiagnosed and undertreated.4 In fact, an estimated 20 million Americans are living with PAD, but only 8.5 million are currently diagnosed.5 While it usually starts asymptomatically, PAD can progress to severe symptoms and require revascularization to avoid amputation.6 PAD is the leading cause of amputations in the U.S. and results in high rates of fatal and non-fatal CV events.6

"PAD is a serious condition that is too frequently missed or often not even discussed by patients and their doctors due to lack of awareness and other health conditions that often take priority. It's important to understand the risk factors for PAD, including conditions such as diabetes, smoking and high blood pressure," said Ryan Gough, Executive Director of the Partnership to Advance Cardiovascular Health**, a heart patient advocacy organization. "There's been a long-standing need across the healthcare community for increased education around PAD and better access to screening and innovative treatments. This is especially critical for patients in underserved communities, who are often at even greater risk for serious complications like amputation."

Amputations are a devastating complication of PAD and are associated with high mortality, despite being largely preventable.6 In recent years, the rate of amputations in the U.S. has been increasing,7 with studies showing Black Americans who have a higher prevalence of asymptomatic PAD, less access to quality vascular care6, and are at risk for delays in care8 are up to four times more likely to have an amputation as a result of PAD compared to White Americans.1

CLICK TO TWEET: #DYK Peripheral Artery Disease #PAD impacts 20M Americans and is the leading cause of amputations in the U.S., with rates continuing to rise?Learn more about PAD:bit.ly/3mjzSBT

XARELTO now has nine indications in the U.S. the most of any direct oral anticoagulant (DOAC). Today's approval is based on the Phase 3 VOYAGER PAD trial, which demonstrated the XARELTO vascular dose (2.5 mg twice daily plus aspirin 100 mg once daily) reduced the risk of major adverse limb and cardiovascular events by 15 percent in patients with symptomatic PAD post-LER compared to aspirin alone.9 The VOYAGER PAD trial saw no significant difference in TIMIi major bleeding between XARELTO with aspirin compared to aspirin alone. The results from the VOYAGER PAD study complement findings from the landmark Phase 3 COMPASS trial, which also examined the dual pathway approach of XARELTO with aspirinin CAD and/or PAD patients and further supports this FDA label extension in PAD patients.10 Data from the Phase 3 COMPASS trial resulted in FDA approval in 2018 to reduce the risk of major cardiovascular events, such as heart attack, stroke and cardiovascular death in people with chronic PAD and CAD.10While there were more major bleeds with the XARELTO vascular dose in COMPASS, there was no significant difference in rates of fatal bleeding, intracranial bleeding or symptomatic bleeding into a critical organ.9,10

"We're thrilled to bring XARELTO to even more patients with PAD who have been living for two decades without any new innovation in the antithrombotic space," said James List, M.D., Ph.D., Global Therapeutic Area Head, Cardiovascular and Metabolism, Janssen Research & Development, LLC. "Today's approval underscores Janssen's commitment to transform care for people living with PAD and make XARELTO available to even more patients in need."

i Thrombolysis in Myocardial Infarction

About VOYAGER PAD

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 the XARELTO vascular dose (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 administered at the treating physician's discretion. Patients were followed for a median of 28 months.

The VOYAGER PAD study met its primary efficacy and principal safety endpoints, demonstrating the XARELTO vascular dose was superior to aspirin alone in reducing the risk of major adverse limb and cardiovascular events by 15 percent in patients with symptomatic PAD after lower-extremity revascularization. The benefit of adding XARELTO to aspirin was apparent early, was consistent among major subgroups and continued to accrue over time. There was no significant increase in TIMImajor bleeding observed in patients treated with the XARELTO vascular dose compared to aspirin alone (2.65 percent vs. 1.87 percent respectively).

More on COMPASS

COMPASS, the largest clinical study of XARELTOto date, enrolled a total of 27,395 patients with chronic CAD and/or PAD. Patients were randomized in a 1:1:1 ratio, with one group receiving the XARELTOvascular dose (2.5 mg twice daily plus aspirin 100 mg once daily), another group receiving rivaroxaban5 mg twice daily, and the final group receiving aspirin 100 mg once daily. COMPASS was stopped approximately one year ahead of schedule due to efficacy.

COMPASS met its primary efficacy endpoint, with the XARELTO vascular dose shown to be superior to aspirin alone, reducing major CV events by 24 percent. This finding was driven by a robust 42 percent reduction in any stroke and 22 percent reduction in CV death. While the risk of major bleeding was significantly higher in patients taking the XARELTO vascular dose compared to aspirin alone, there was no significant difference between the treatment groups in fatal bleeds, intracranial bleeds, symptomatic bleeding into a critical organ, or bleeding into the surgical site requiring reoperation.

WHAT IS XARELTO?

XARELTOis a prescription medicine used to:

XARELTOis used with low dose aspirin to:

It is not known if XARELTOis 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:

Do not stop taking XARELTO without talking to the doctor who prescribes it for you. Stopping XARELTO increases your risk of having a stroke. If you have to stop taking XARELTO, your doctor may prescribe another blood thinner medicine to prevent a blood clot from forming.

Tell your doctorif 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 doctorright away if you have:

XARELTO is not for use in people with artificial heart valves.

XARELTO is not for use in people with antiphospholipid syndrome (APS), especially with positive triple antibody testing.

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 dentiststhat 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?

If you take XARELTO for:

WHAT ARE THE POSSIBLE SIDE EFFECTS OF XARELTO?

XARELTO may cause serious side effects:

The most common side effect of XARELTOwas bleeding.

Call your doctor for medical advice about side effects. You may report side effects to the 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 read full Prescribing Information, including Boxed Warnings, and Medication Guide for XARELTO.

Trademarks are those of their respective owners.

cp-53637v7

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 http://www.janssen.com/cardiovascular-and-metabolism.

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 http://www.janssen.com. Follow us at http://www.twitter.com/JanssenUS and http://www.twitter.com/JanssenGlobal. Janssen Research & Development, LLC, is part 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 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 January 3, 2021, 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 http://www.sec.gov, http://www.jnj.com or on request from Johnson & Johnson. None of 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.

1.

Racial Disparities in Vascular Care. (n.d.). Retrieved June 17, 2021 fromhttps://cardiovascularcoalition.com/our-patients/racial-disparities-in-vascular-care/.

2.

Norgren L, Hiatt WR,DormandyJA, Hirsch AT, et al. The next 10 years in the management of peripheral artery disease: perspectives from the 'PAD 2009' Conference.EurVascEndovasc Surg.2010;40(3):375-380.

3.

American Heart Association. About Peripheral Artery Disease (PAD). Retrieved April29, 2021fromhttps://www.heart.org/en/health-topics/peripheral-artery-disease/about-peripheral-artery-disease-pad.

4.

Afzal N, Sohn S, Scott CG, Liu H,KulloIJ, Arruda-Olson AM. Surveillance of peripheral arterial disease cases using natural language processing of clinical notes.AMIA Jt SummitsTranslSci Proc.2017;2017:28-36.Retrieved June 2, 2021 from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543345/#r2-2609862.

5.

American Heart Association. Peripheral Artery Disease (PAD) ResourcesForPatients and Providers. Retrieved April29, 2021fromhttps://www.heart.org/en/health-topics/peripheral-artery-disease/pad-resources.

6.

Creager MA, Matsushita K, Arya S, et al. Reducing nontraumatic lower-extremity amputations by 20% by 2030: time to get to our feet: a policy statement from the American Heart Association. Circulation. 2021;143(17):e875-e891. doi:10.1161/CIR.000000000000096.

7.

SchuivensPME, Buijs M,Boonman-de Winter L, et al. Impact of the COVID-19 lockdown strategy on vascular surgery practice: more major amputations than usual.AnnVascSurg.2020;69:74-79.doi:10.1016/j.avsg.2020.07.025. Retrieved June 2, 2021 fromhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402273/.

8.

WintaGhidei, Tracie C. Collins, "African Americans and Peripheral Arterial Disease: A Review Article", International Scholarly Research Notices, vol. 2012, Article ID 165653, 9 pages, 2012.https://doi.org/10.5402/2012/165653

9.

BonacaMP, Bauersachs RM, Anand SS, et al. Rivaroxaban in peripheral artery disease after revascularization. N Engl J Med. 2020 May 21;382(21):1994-2004.

10.

Eikelboom JW, Connolly SJ, Bosch J, et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med. 2017 Oct 5;377:1319-1330.

*Dr. Bonaca is affiliated with CPC Clinical Research, which was provided a grant for their participation in the Phase 3 VOYAGER PAD clinical trial.

**The Partnership to Advance Cardiovascular Health was provided a grant to help support their PAD disease awareness program.

SOURCE Janssen Pharmaceutical Companies of Johnson & Johnson

https://www.janssen.com/

Read the original:
FDA Approves Expanded Peripheral Artery Disease (PAD) Indication for XARELTO (rivaroxaban) Plus Aspirin to Include Patients After Lower-Extremity...