New England Journal of Medicine publishes phase III data showing single-dose Xofluza significantly reduces influenza virus transmission
Roche (RHHBY) has published phase III CENTERSTONE trial results for Xofluza (baloxavir marboxil) in the New England Journal of Medicine, demonstrating significant reduction in influenza virus transmission. The trial met its primary endpoint, showing a 32% reduction in the odds of virus transmission from infected individuals to untreated household members with a single oral dose.
While the key secondary endpoint of reducing symptomatic transmission showed clinically meaningful reduction, it did not reach statistical significance. The drug demonstrated a favorable safety profile with no new safety concerns identified.
The findings have been submitted to both the FDA and EMA for review. This breakthrough is particularly significant as approximately one-third of all influenza transmission occurs within households, with seasonal influenza affecting an estimated one billion people worldwide annually, causing millions of hospitalizations and up to 650,000 deaths globally.
Roche (RHHBY) ha pubblicato i risultati dello studio di fase III CENTERSTONE su Xofluza (baloxavir marboxil) sul New England Journal of Medicine, dimostrando una significativa riduzione della trasmissione del virus dell'influenza. Lo studio ha raggiunto l'endpoint primario, mostrando una riduzione del 32% nelle probabilità di trasmissione del virus da individui infetti a membri della famiglia non trattati con una singola dose orale.
Pur avendo mostrato una riduzione clinicamente significativa nella trasmissione sintomatica, l'endpoint secondario chiave non ha raggiunto la significatività statistica. Il farmaco ha mostrato un profilo di sicurezza favorevole senza nuove preoccupazioni emerse.
I risultati sono stati sottoposti sia alla FDA che all'EMA per la revisione. Questa scoperta è particolarmente importante considerando che circa un terzo di tutte le trasmissioni di influenza avviene all'interno delle famiglie, con l'influenza stagionale che colpisce circa un miliardo di persone ogni anno nel mondo, causando milioni di ricoveri e fino a 650.000 decessi globalmente.
Roche (RHHBY) ha publicado los resultados del ensayo de fase III CENTERSTONE sobre Xofluza (baloxavir marboxil) en el New England Journal of Medicine, demostrando una reducción significativa en la transmisión del virus de la influenza. El ensayo cumplió su objetivo principal, mostrando una reducción del 32% en las probabilidades de transmisión del virus de personas infectadas a miembros del hogar no tratados con una sola dosis oral.
Aunque el objetivo secundario clave de reducir la transmisión sintomática mostró una reducción clínicamente significativa, no alcanzó significancia estadística. El medicamento mostró un perfil de seguridad favorable sin nuevas preocupaciones identificadas.
Los hallazgos han sido presentados tanto a la FDA como a la EMA para su revisión. Este avance es especialmente relevante ya que aproximadamente un tercio de toda la transmisión de influenza ocurre dentro de los hogares, con la influenza estacional afectando a cerca de mil millones de personas anualmente en todo el mundo, causando millones de hospitalizaciones y hasta 650,000 muertes globalmente.
로슈(RHHBY)는 Xofluza(발록사비르 말복실)에 대한 3상 CENTERSTONE 임상시험 결과를 New England Journal of Medicine에 발표하며 인플루엔자 바이러스 전파를 현저히 감소시켰음을 입증했습니다. 본 임상시험은 1회 경구 투여로 감염된 환자에서 비치료 가정 내 구성원으로의 바이러스 전파 확률을 32% 감소시키는 1차 목표를 달성했습니다.
증상 전파 감소라는 주요 2차 목표는 임상적으로 의미 있는 감소를 보였으나 통계적 유의성은 확보하지 못했습니다. 약물은 새로운 안전성 문제 없이 우수한 안전성 프로파일을 나타냈습니다.
이 결과는 FDA와 EMA에 검토를 위해 제출되었습니다. 이번 성과는 인플루엔자 전파의 약 3분의 1이 가정 내에서 발생하며, 계절성 인플루엔자가 전 세계적으로 연간 약 10억 명에게 영향을 미쳐 수백만 명이 입원하고 최대 65만 명이 사망하는 상황에서 특히 중요한 돌파구입니다.
Roche (RHHBY) a publié les résultats de l'essai de phase III CENTERSTONE sur Xofluza (baloxavir marboxil) dans le New England Journal of Medicine, démontrant une réduction significative de la transmission du virus de la grippe. L'essai a atteint son critère principal, montrant une réduction de 32% des chances de transmission du virus des personnes infectées aux membres du foyer non traités après une dose orale unique.
Bien que le critère secondaire clé de réduction de la transmission symptomatique ait montré une diminution cliniquement significative, il n’a pas atteint la signification statistique. Le médicament a présenté un profil de sécurité favorable sans nouvelles préoccupations identifiées.
Les résultats ont été soumis à la fois à la FDA et à l’EMA pour examen. Cette avancée est particulièrement importante car environ un tiers de toutes les transmissions de la grippe se produisent au sein des foyers, la grippe saisonnière affectant environ un milliard de personnes dans le monde chaque année, provoquant des millions d’hospitalisations et jusqu’à 650 000 décès à l’échelle mondiale.
Roche (RHHBY) hat die Ergebnisse der Phase-III-Studie CENTERSTONE zu Xofluza (Baloxavir Marboxil) im New England Journal of Medicine veröffentlicht, die eine signifikante Reduktion der Übertragung des Influenzavirus zeigen. Die Studie erreichte den primären Endpunkt und zeigte eine 32%ige Verringerung der Wahrscheinlichkeit der Virusübertragung von infizierten Personen auf unbehandelte Haushaltsmitglieder nach einer einmaligen oralen Gabe.
Der wichtige sekundäre Endpunkt der Reduktion der symptomatischen Übertragung zeigte eine klinisch bedeutsame Abnahme, erreichte jedoch keine statistische Signifikanz. Das Medikament zeigte ein günstiges Sicherheitsprofil ohne neue Sicherheitsbedenken.
Die Ergebnisse wurden sowohl der FDA als auch der EMA zur Prüfung vorgelegt. Dieser Durchbruch ist besonders bedeutsam, da etwa ein Drittel aller Influenzavirus-Übertragungen innerhalb von Haushalten erfolgt. Die saisonale Influenza betrifft weltweit schätzungsweise eine Milliarde Menschen jährlich, verursacht Millionen von Krankenhausaufenthalten und bis zu 650.000 Todesfälle.
- First demonstration of an antiviral reducing respiratory virus transmission by 32%
- Favorable safety profile with no new safety concerns
- Potential new indication pending FDA and EMA review
- Addresses significant market need with 1 billion annual influenza cases globally
- Secondary endpoint for symptomatic transmission reduction did not reach statistical significance
- Detailed results from the CENTERSTONE trial show treatment with Xofluza reduced the odds of transmission, or spread of the influenza virus, from an infected person to household members by
32% 1 - CENTERSTONE is the first global phase III trial that demonstrates the benefit of an antiviral in reducing the spread of a respiratory virus1
- Reducing the spread of infection within households could help limit transmission within institutions and communities, potentially easing the burden of both seasonal and pandemic influenza on healthcare systems2,3
Basel, 25 April 2025 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the New England Journal of Medicine (NEJM) has published a detailed analysis of the phase III CENTERSTONE trial of Xofluza® (baloxavir marboxil).1 The trial met its primary endpoint, showing a single, oral dose of Xofluza taken by people infected with influenza reduced the odds of untreated household members contracting the virus by
“This trial is the first to demonstrate an antiviral effect that reduces transmission of influenza viruses within a household. This result may potentially have broad-reaching implications for public health,” said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development. “This publication reminds us of the ongoing societal need for solutions that can help ease the burden of influenza on society.”
Results from the CENTERSTONE trial have been submitted to health authorities, including the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA).
Influenza poses a significant health and economic burden, particularly for those at high risk of influenza-related complications.2,3 Every year, seasonal influenza infects an estimated one billion people worldwide and causes millions of hospitalisations, with up to 650,000 deaths globally.2,3 Approximately one-third of all influenza virus transmission occurs within households.4 As many as
This project has been supported in whole or in part with federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority, under Other Transaction Agreement number: HHSO100201800036C.
About CENTERSTONE8
The CENTERSTONE trial [NCT03969212] was a global phase III trial investigating the efficacy of single-dose Xofluza, taken within 48 hours of symptom onset, to reduce the onward transmission of influenza within households. The trial was conducted in 272 sites across the globe, with over 4,000 participants, and involved otherwise healthy patients from five to 64 years who had been diagnosed with influenza via a polymerase chain reaction (PCR) or rapid influenza diagnostic test, known as index patients (IPs), and those within their household (known as household contacts, HHCs). The design of this randomised, placebo-controlled trial was developed with input from the US FDA and leading experts in influenza.
The primary endpoint was the proportion of HHCs who tested positive for influenza within five days after the IP had been treated with either Xofluza or placebo (1:1 randomisation within 48 hours of symptoms onset). There was a
For the key secondary endpoint of symptomatic transmission of influenza virus by day five, Xofluza showed a clinically meaningful reduction, although statistical significance was not reached. There was a
About Xofluza® (baloxavir marboxil)
Xofluza is a first-in-class, single-dose oral medicine with an innovative mechanism of action designed to block viral replication by inhibiting the cap-dependent endonuclease protein, reducing the duration of infectiousness and disease. Xofluza has demonstrated effectiveness against a wide range of influenza viruses, including in vitro and in vivo activity against oseltamivir-resistant strains and avian strains (H7N9, H5N1) in non-clinical studies. 9,10,11
Xofluza is approved in more than 75 countries for the treatment of uncomplicated influenza types A and B.12 In several countries, Xofluza is approved for the treatment of influenza in otherwise healthy patients and as a preventative treatment (post-exposure prophylaxis). Xofluza represents the first innovation in mechanism of action for an influenza antiviral approved in almost 20 years for treatment in children, adolescents, and adults.14
Robust clinical evidence has demonstrated the clinical benefit of single-dose Xofluza in the treatment of influenza in several populations (otherwise healthy and high-risk individuals and, children) and as post-exposure prophylaxis in the EU for children aged one and older, and in the US and China aged five and older.11,13,15,16,17 Xofluza was also studied in a phase III trial in children under the age of one year (NCT03653364).18
Xofluza was discovered by Shionogi & Co., Ltd. and is being further developed and commercialised globally in collaboration with the Roche Group (which includes Genentech in the US). Under the terms of this agreement, Roche holds worldwide rights to Xofluza excluding Japan and Taiwan, which will be retained exclusively by Shionogi & Co., Ltd.
About Roche in Influenza
Influenza is a serious infectious disease and represents a significant burden to public health through annual epidemics and periodic pandemics.2,3 Seasonal epidemics result in an estimated one billion cases, millions of hospitalisations, and up to 650,000 deaths globally every year.2,3
Roche has a long history of developing transformative medicines and diagnostics that contribute to public health. Roche’s Tamiflu® (oseltamivir) has significantly improved the treatment of seasonal influenza and pandemic management. The Roche Diagnostics portfolio includes a range of tests and solutions that help differentiate influenza from other respiratory viruses, including the cobas® Respiratory flex test, the cobas liat system, and the recently acquired LumiraDx point of care platform.
Roche is committed to addressing the unmet need in influenza through its agreement with Shionogi & Co., Ltd. to develop and commercialise Xofluza® (baloxavir marboxil).
About Roche
Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice.
For over 125 years, sustainability has been an integral part of Roche’s business. As a science-driven company, our greatest contribution to society is developing innovative medicines and diagnostics that help people live healthier lives. Roche is committed to the Science Based Targets initiative and the Sustainable Markets Initiative to achieve net zero by 2045.
Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan.
For more information, please visit www.roche.com.
All trademarks used or mentioned in this release are protected by law.
References
[1] Monto, AS. et al. Efficacy of Baloxavir Treatment in Preventing Transmission of Influenza. New England Journal of Medicine [Internet; cited April 2025]. Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa2413156
[2] ECDC. Factsheet about seasonal influenza. [Internet; cited April 2025]. Available from: https://www.ecdc.europa.eu/en/seasonal-influenza/facts/factsheet.
[3] World Health Organization (WHO). Influenza (Seasonal). [Internet; cited April 2025]. Available from: http://www.who.int/en/news-room/fact-sheets/detail/influenza-(seasonal).
[4] Klick .B et al. Optimal design of studies of influenza transmission in households. I: Case-ascertained studies. 2011 Epidemiology and Infection, 140(1), pp. 106–114.
[5] Blanchet Zumofen, M.-H., et al. Impact of influenza and influenza-like illness on work productivity outcomes: A systematic literature review. 2022, PharmacoEconomics, 41(3), pp. 253–273.
[6] WHO. Joint Statement - Influenza season epidemic kicks off early in Europe as concerns over RSV rise and COVID-19 is Still a Threat. [Internet; cited April 2025]. Available from: https://www.who.int/europe/news/item/01-12-2022-joint-statement---influenza-season-epidemic-kicks-off-early-in-europe-as-concerns-over-rsv-rise-and-covid-19-is-still-a-threat.
[7] WHO. Global Influenza Strategy 2019-2030. [Internet; cited April 2025]. Available from: https://www.who.int/publications/i/item/9789241515320.
[8] Clinical Trials.gov. Study to assess the efficacy of baloxavir marboxil versus placebo to reduce onward transmission of Influenza A or B in households [Internet; cited April 2025]. Available from: https://www.clinicaltrials.gov/study/NCT03969212.
[9] Hayden F, et al. Baloxavir marboxil for uncomplicated influenza in adults and adolescents. New England Journal of Medicine 2018;379:913–923.
[10] Noshi T, et al. In vitro characterization of baloxavir acid, a first-in-class cap-dependent endonuclease inhibitor of the influenza virus polymerase PA subunit. Antiviral Research. 2018;160:109-117.
[11] Taniguchi K, et al. Inhibition of avian-origin influenza A(H7N9) virus by the novel cap-dependent endonuclease inhibitor baloxavir marboxil. Scientific Reports. 2019;9:3466.
[12] Roche data on file.
[13] European Medicines Agency. Summary of product characteristics, Xofluza. 2021. [Internet; cited April 2025]. Available from:https://www.ema.europa.eu/en/medicines/human/EPAR/xofluza#product-info
[14] Roche.com. Roche’s Xofluza approved by the European Commission for the treatment of influenza, the first new influenza antiviral for patients in almost 20 years. [Internet; cited April 2025]. Available from: https://www.roche.com/media/releases/med-cor-2021-01-11.
[15] Baker J, et al. Baloxavir marboxil single-dose treatment in influenza-infected children: A randomized, double-blind, active controlled phase 3 safety and efficacy trial (miniSTONE-2). The Pediatric Infectious Disease Journal. 2020;39(8):700-705.
[16] Ikematsu H, et al. Baloxavir marboxil for Prophylaxis against Influenza in Household Contacts. New England Journal of Medicine. 2020;383:309-320.
[17] Ison, M et al. Early treatment with baloxavir marboxil in high-risk adolescent and adult outpatients with uncomplicated influenza (CAPSTONE-2): a randomised, placebo-controlled, phase 3 trial. Lancet Infectious Diseases 2020;20(10):1204–14.
[18] Clinicaltrials.gov. Study to assess the safety, pharmacokinetics, and efficacy of baloxavir marboxil in healthy pediatric participants from birth to < 1 year with influenza-like symptoms. [Internet; cited April 2025]. Available from: https://clinicaltrials.gov/ct2/show/NCT03653364.
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FAQ
What were the main results of Roche's (RHHBY) CENTERSTONE phase III trial for Xofluza?
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