RARITAN, NJ - The Janssen Pharmaceutical Companies of Johnson & Johnson announced new data from the Phase 3 UNIVERSE study showing treatment with XARELTO (rivaroxaban) in an oral suspension formulation, compared to treatment with aspirin, was associated with numerically fewer blood clots and clinical events strongly associated with blood clots in pediatric patients (aged 2-8 years) who have undergone the Fontan procedure. [1] These findings, which were published this month in the Journal of the American Heart Association and included in a recent New Drug Application submitted to the U.S. Food and Drug Administration, also found treatment with XARELTO was associated with a similar safety profile compared to aspirin.

The Fontan procedure is performed in children with congenital heart disease who have a single functioning ventricle to redirect blood flow to the lungs to be reoxygenated. Children who undergo the Fontan procedure often face significant morbidity and mortality stemming from thrombotic events, especially during the critical 3- to 12-month period following the procedure. While it is common for physicians to prescribe aspirin, there are limited data regarding aspirin resistance or the optimal dose for thromboprophylaxis in children.

'For years, health care providers have had limited options to help reduce potentially fatal thrombotic events that often occur in young children following the Fontan procedure,' saidBrian W. McCrindle, M.D., MPH, Pediatric Cardiologist at the Hospital for Sick Children in Toronto. [i] 'We now not only have data suggesting that rivaroxaban has a similar positive effect and safety as aspirin, but we also have identified an age-appropriate formulation with precise weight-based dosing to help manage our young patients during a critical time.'

The UNIVERSE study was conducted to determine the comparative efficacy and safety of XARELTO versus aspirin and to provide clear evidence-based dosing recommendations in this pediatric population.

The study was conducted in two parts: Part A evaluated pharmacokinetic (PK) and pharmacodynamic (PD) properties of XARELTO, and Part B examined the safety and efficacy of XARELTO compared to aspirin when used for thromboprophylaxis for 12 months. The primary safety outcome was major bleeding events defined by the International Society on Thrombosis and Haemostasis (ISTH). The secondary safety outcomes were clinically relevant non-major bleeding and trivial (minimal) bleeding events. The primary efficacy outcome was any thrombotic event (venous or arterial) defined as the appearance of a new thrombotic burden within the cardiovascular system noted on either routine surveillance or clinically indicated imaging, or the occurrence of a clinical event known to be strongly associated with thrombus (e.g., stroke or pulmonary embolism). All thrombotic and safety events were adjudicated by the central independent adjudication committee (CIAC).

Key findings:

A comparable and low prevalence of bleeding events was observed withXARELTO compared to aspirin. There was one major non-fatal bleeding event (nosebleed) with XARELTO, and compared to aspirin, a slightly lower prevalence of non-major clinically relevant bleeding (6 vs. 9 percent of participants) and trivial bleeding (33 vs. 35 percent of participants). The prevalence and pattern of adverse events were comparable between the two groups.

There were fewer thrombotic events withXARELTO, though the study was not powered for efficacy outcomes (post-hoc log-rank test p=0.095). In the XARELTO group, one patient had a pulmonary embolism (2 percent event rate). In the XARELTO Part A group, there was one venous thrombotic event for an overall rate of 3 percent in the XARELTO groups combined. In the aspirin group, one participant had ischemic stroke and two had venous thrombosis (9 percent overall event rate).

'The promise of the EXPLORER research program for XARELTO was to uncover new insights into how the medical community can help improve the care of patients who are faced with thrombotic risk, from young to old,' said James List, M.D., Ph.D., Global Therapeutic Area Head, Cardiovascular, Metabolism, & Retina, Janssen Research & Development, LLC. 'The UNIVERSE study is another example of our fulfillment of that promise, and we're optimistic these findings will generate greater understanding and help to inform guidance for physicians managing thrombotic complications in these vulnerable and high-risk pediatric patients.'

UNIVERSE study design

A randomized, multicenter, open-label, active controlled, two-part, Phase 3 study, UNIVERSE examined the use of a novel, oral liquid 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, 112 participants were enrolled across 35 sites in 10 countries.

During Part A of the study, PK and PD blood samples were collected on days 1 and 4 to determine if the patient could continue receiving the study drug for the 12-month study period. During Part B, patients were randomized in a 2:1 ratio to receive either body weight-adjusted XARELTO, administered orally twice daily (dose regimen that matched the exposure range in adults treated with rivaroxaban 10 mg once daily), or aspirin, given once daily (approximately 5 mg/kg). The primary safety outcome was major bleeding events, and the primary efficacy outcome was any thrombotic event, including venous or arterial clots, or any thromboembolic event, including stroke or a pulmonary embolism. Patients had additional PK and PD samples collected at months 3 and 12. PK/PD results will be published at a later date.

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/JanssenUS and https://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 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 www.sec.gov, 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] The UNIVERSE study was not powered to demonstrate efficacy results.

[i] Dr. McCrindle is affiliated with the Hospital for Sick Children in Toronto, which was provided payment for their participation in the Phase 3 UNIVERSE clinical trial.

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