GlobeNewswire Inc | Apr 26, 2021 02:00AM EDT

April 26, 2021

Nirsevimab demonstrated protectionagainst respiratory syncytial virus diseasein healthy infants in Phase 3 trial

-- Respiratory Syncytial Virus (RSV) is the leading cause of hospitalization in all infants.1-5 -- Nirsevimab is being investigated as a first-in-class single dose immunization to provide protection for all infants entering their first RSV season. -- Nirsevimab met its Phase 3 primary endpoint earlier than anticipated; regulatory submissions for all-infant indication to begin in 2022.

PARIS April 26, 2021 Positive topline results from the Phase 3 MELODY trial showed nirsevimab reduced lower respiratory tract infections (LRTI) requiring medical attention (inpatient or outpatient) due to respiratory syncytial virus (RSV) in healthy preterm and term infants. RSV is the most common cause of LRTI and the leading cause of hospitalizations in all infants.1-5

Nirsevimab reached its primary endpoint, achieving a statistically significant absolute reduction of LRTI caused by RSV in healthy preterm and term infants compared to placebo through a typical RSV season. No clinically meaningful differences in safety results between the nirsevimab and placebo groups were seen. The overall safety profile of nirsevimab in the trial remains consistent with previously reported results.

Results will be presented at an upcoming scientific congress and are anticipated to form the basis of regulatory submissions.

Despite respiratory syncytial virus being the leading cause of pneumonia and bronchiolitis in the first year of life, there is no routine preventative option currently approved for all infants, said Dr William Muller, Associate Professor, Pediatrics,Northwestern University Feinberg School of Medicine and Scientific Director, Clinical and Community Trials,Ann & Robert H. Lurie Childrens Hospital of Chicago, Illinois, US and primary investigator of the MELODY Phase III trial.These exciting trial data demonstrate the potential for nirsevimab to change the prevention landscape not only by providing protection to a broad population of infants across the full respiratory syncytial virus season, but also by achieving this with a single dose.

Nirsevimab, being developed in partnership with AstraZeneca, is the first investigational extended half-life monoclonal antibody (mAb) aimingto protect all infants entering their first RSV season, when they are at highest risk for severe RSV disease.1,6,7With nirsevimab, a protective antibody is administered directly to the infant with the goal of providing rapid protection.

Incontrast to other options for RSV under development, such as maternal vaccines,nirsevimab was designed to be administered at birth to infants born during the RSV season or at the seasons start for infants born prior to the season.

Respiratory syncytial virus is the leading cause of hospitalizations in all infants, said Jean-Franois Toussaint, GlobalHeadof Research and Development,Sanofi Pasteur. In fact, most hospitalizations occur in otherwise healthy infants born at term. Its clear all infants need protection from RSV, and we hope nirsevimab becomes an important addition to routine immunization schedules.

These ground-breaking results mark a major scientific advancement in our effortto provide protection against respiratory syncytial virus forall infants. Nearly all children will contract the virus before age two, leading to nearly 30 million acute lower respiratory tract infections globally each year, said Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca. Nirsevimab has the potential to provide a significant public health benefit as the first respiratory syncytial virus immunization for the general infant population, and these data bring us one step closer to delivering nirsevimab to infants worldwide.

Nirsevimab is also being evaluated in a Phase II/III MEDLEY trial which will assess the safety and tolerability of nirsevimab compared to Synagis (palivizumab) among preterm infants and children with chronic lung disease (CLD) and congenital heart disease (CHD) entering their first and second RSV seasons. The Phase II/III trial is also expected to complete early with first data anticipated in the coming months.

About the Phase 3 MELODY study

The Phase 3 study is a randomized, placebo-controlled trial designed to determinethe incidence of medically attended lower respiratory tract infections (LRTI)due to Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) confirmed RSV through 150 days post-dose versus placeboin healthy infants entering their first RSV season.Healthy late preterm and term infants of 35 weeks 0 daysor greater gestational age were randomised (2:1) to receive a single 50mg(in infants weighing <5kg) or 100mg (in infants weighing 5kg)intramuscular injection ofnirsevimabor placebo. Between July 2019 andFebruary 2021 approximately1,500infants were dosedwith eithernirsevimabor placeboat the RSV season start. Research was conducted by AstraZenecain21countries.An additional 1,500 infants will be enrolled in the Northern and Southern Hemispheres to complete the safety evaluation.

Last July detailed results from the positive Phase 2b trial for nirsevimab were published in the NEJM which showed a significant reduction in medically attended lower respiratory tract infections, mainly bronchiolitis and pneumonia, and hospitalizations caused by respiratory syncytial virus (RSV) in healthy preterm infants.

About RSV

RSV is a common, contagious virus that infects the respiratory tract, causing millions of hospitalizations globally in infants, and is the most common cause of bronchiolitis and pneumonia in children younger than one year.1-5,8,9 Hospitalization rates due to RSV infection are consistently highest in the first year of life with infants under one year representing 75% of RSV hospitalizations in children under 5 years.2,10,11 Most hospitalizations for RSV occur in otherwise healthy infants born at term.2,11-13 Moreover, medically-attended LRTIs are associated with increased costs to the healthcare system.14

About nirsevimab

Nirsevimab is an extended half-life RSV mAb being developed as a passive immunization for the prevention of LRTI caused by RSV. It is designed for use in a broad infant population, including all infants experiencing their first RSV season and infants with congenital heart disease or chronic lung disease entering their first and second RSV season.15,16

Nirsevimab is designed to provide RSV protection via an antibody given directly to an infantto help prevent LRTI caused by RSV, unlike active immunization, where a persons immune system is activated to prevent or fight infection through a vaccine.17 Passive immunization could offer rapid protection unlike active immunization, which can take weeks to develop protection.17

In March 2017, AstraZeneca and Sanofi announced anagreementto develop and commercialize nirsevimab. Under the terms of the agreement, AstraZeneca leads all development activity through initial approvals and retains manufacturing activities and Sanofi will lead commercialization activities.Nirsevimab is currently under clinical investigation and its safety and efficacy have not been reviewed by any regulatory authority.

Editors note: In January 2021, nirsevimab received the Promising Innovative Medicine (PIM) Designation from the UK Medicines and Healthcare Products Regulatory Agency (MHRA)and was also granted the Breakthrough Therapy Designation (BTD) by the China Center for Drug Evaluation (CDE) under the National Medical Products Administration.In February 2019, the US Food and Drug Administration grantedBreakthrough Therapy Designationfor nirsevimab for the prevention of LRTI caused by RSV, and the European Medicines Agency (EMA) granted access to itsPRIorityMEdicines (PRIME) schemefor the same indication.In Japan, nirsevimab was also selected by the Japan Agency for Medical Research and Development (AMED) as a medicine for prioritized development under the Project for Drug Selection to Promote New Drug Development in Pediatrics.



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1. Shi T, et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. Lancet 2017; 390: 94658. 2. Rha B et al. Respiratory Syncytial VirusAssociated Hospitalizations Among Young Children: 20152016. Pediatrics. 2020;146(1):e20193611.3. Leader S., et al. Recent trends in severe respiratory syncytial virus (RSV) among US infants, 1997 to 2000. J Pediatrics. 2003; vol 143:S127-S132.4. Hall CB. The Burgeoning Burden of Respiratory Syncytial Virus Among Children. Infect Disord Drug Targets. 2012;12(2):92-975. Reeves RM et al. Estimating the burden of respiratory syncytial virus (RSV) on respiratory hospital admissions in children less than five years of age in England, 2007-2012. Influenza Other Respir Viruses. 2017;11(2):122-1296. Sanofi Pasteur. Data on file. Sanofi Pasteur MarketScan Internal Analysis7. Rose E B et al. Respiratory Syncytial Virus Seasonality United States, 20142017. MMWR Morb Mortal Wkly Rep. 2018;67:71768. Piedimonte G, Perez MK. Respiratory Syncytial Virus Infection and Bronchiolitis. Pediatr Rev. 2014;35(12):519-5309. Oymar K et al. Acute bronchiolitis in infants, a review. Scand J Trauma ResuscEmerg Med. 2014;22:2310. Hall CB, et al. The Burden of Respiratory Syncytial Virus Infection in Young Children. N Engl J Med. 2009;360(6):58859811. Hall CB, et al. Respiratory syncytial virus-associated hospitalizations among children less than 24 months of age. Pediatrics. 2013;132(2):e341-e34812. Arriola CS et al. Estimated Burden of Community-Onset Respiratory Syncytial VirusAssociated Hospitalizations Among Children Aged <2 Years in the United States, 201415. J Pediatric Infect Dis Soc. 2019:DOI: 10.1093/jpids/piz08713. Krilov LR et al. Impact of the 2014 American Academy of Pediatrics Immunoprophylaxis Policy on the Rate, Severity, and Cost of Respiratory Syncytial Virus Hospitalizations among Preterm Infants. Am J Perinatol. 2020 Jan;37(2):174-18314. Leistner R, et al. Attributable Costs of Ventilator-Associated Lower Respiratory Tract Infection (LRTI) Acquired on Intensive Care Units: a Retrospectively Matched Cohort Study. Antimicrobial Resistance and Infection Control, vol. 2, no. 1, 4 Apr. 2013, p. 13., doi:10.1186/2047-2994-2-1315. Clinicaltrials.gov. A Study to Evaluate the Safety and Efficacy of MEDI8897 for the Prevention of Medically Attended RSV LRTI in Healthy Late Preterm and Term Infants (MELODY). https://clinicaltrials.gov/ct2/show/NCT03979313. Accessed April 2021.16. Clinicaltrials.gov. A Study to Evaluate the Safety of MEDI8897 for the Prevention of Medically Attended Respiratory Syncytial Virus (RSV) Lower Respiratory Track Infection (LRTI) in High-risk Children. https://clinicaltrials.gov/ct2/show/NCT03959488. Accessed April 2021.17. Centers for Disease Control and Prevention. Vaccines & Immunizations. August 18, 2017. https://www.cdc.gov/vaccines/vac-gen/immunity-types.htm. Accessed April 2021

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