READING, England--(BUSINESS WIRE)--Following European Commission approval earlier this month, the Medicines and Healthcare products Regulatory Agency (MHRA) has approved Beyfortus®▼ (nirsevimab) for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in newborns and infants during their first RSV season. RSV is a common and highly contagious seasonal virus, infecting 90% of children by the age of two.3,4 Nirsevimab is the first and only single-dose RSV protective option for the broad infant population,5 including those born healthy, at term or preterm, or with specific health conditions.6 Nirsevimab is being developed jointly by Sanofi and AstraZeneca.
Thomas Triomphe
Executive Vice President, Vaccines, Sanofi
“Today is a landmark day for RSV prevention, as decades of research and development come together for approval of a broadly protective option against RSV disease. Once launched, nirsevimab will offer parents the ability to help protect their babies during their first RSV season.”
Iskra Reic
Vaccines and Immune Therapies Unit, AstraZeneca
“Nirsevimab is the first single-dose passive immunisation against respiratory syncytial virus to gain approval in Great Britain and is also the first and only preventative option approved for a broad infant population.5 Today’s marketing authorisation of nirsevimab marks a significant achievement for the scientific community and addresses a persistent, global unmet need in RSV prevention.”
The MHRA approved nirsevimab following the European Commission’s approval earlier this month. The approval was based on results from the nirsevimab clinical development programme, including the Phase 3 MELODY, Phase 2/3 MEDLEY and Phase 2b trials. In the MELODY and Phase 2b trials, nirsevimab met its primary endpoint of reducing the incidence of medically attended lower respiratory tract infections (LRTI) caused by RSV during the RSV season vs. placebo with a single dose.1,2,5,7,8,9 The safety profile of nirsevimab was similar to placebo. Nirsevimab also demonstrated a comparable safety and tolerability profile to palivizumab in the Phase 2/3 MEDLEY trial.9,10,11
RSV is the most common cause of LRTI, including bronchiolitis and pneumonia, in infants.12 It is also a leading cause of hospitalisation in all infants, with most hospitalisations for RSV occurring in healthy infants born at term.13,14In the UK, around 30,000 children under the age of five are hospitalised every year due to RSV and it causes approximately 33 deaths per year in children under five.15 The economic impact of RSV is estimated at around £80 million each year in the UK.16
About nirsevimab
Nirsevimab a long-acting antibody designed for all infants for protection against RSV disease from birth through their first RSV season with a single dose, is developed jointly by Sanofi and AstraZeneca.
Nirsevimab has been developed to offer newborns and infants direct RSV protection via an antibody to help prevent LRTI caused by RSV. Monoclonal antibodies do not require the activation of the immune system to help offer timely, rapid and direct protection against the disease.16
Nirsevimab has been granted marketing authorisation in the European Union for the prevention of RSV lower respiratory tract disease in newborns and infants from birth during their first RSV season.
In March 2017, Sanofi and AstraZeneca announced an agreement to develop and commercialise nirsevimab. Under the terms of the agreement, AstraZeneca leads all development and manufacturing activities and Sanofi leads commercialisation activities and records revenue. Under the terms of the global agreement, Sanofi made an upfront payment of €120m, has paid a development milestone of €30m and will pay up to a further €465m upon achievement of certain development and sales-related milestones. The two companies share all costs and profits.
Nirsevimab has been granted designations to facilitate expedited development by several regulatory agencies around the world. These include Breakthrough Therapy Designation by the China Center for Drug Evaluation under the National Medical Products Administration; Breakthrough Therapy Designation from the US Food and Drug Administration; access granted to the European Medicines Agency (EMA) PRIority MEdicines scheme; and has been named “a medicine for prioritised development” under the Project for Drug Selection to Promote New Drug Development in Paediatrics by the Japan Agency for Medical Research and Development (AMED).
About the clinical trials
The Phase 2b trial was a randomised, placebo-controlled trial designed to measure the efficacy of nirsevimab against medically attended LRTI through 150 days post-dose. Healthy preterm infants of 29–35 weeks’ gestation were randomised (2:1) to receive a single 50mg intramuscular injection of nirsevimab or placebo. The primary endpoint was met, reducing the incidence of medically attended LRTI, caused by RSV by 70.1% (95% CI: 52.3, 81.2) compared to placebo. Between November 2016 and December 2017, 1,453 infants were randomised nirsevimab, n=969; placebo, n=484) at the RSV season start. Studies were conducted in both hemispheres, at 164 sites in 23 countries.7,8 Data was published in the New England Journal of Medicine (NEJM) in July 2020. The dosing regimen was recommended based on further exploration of the phase 2b data.7 The subsequent Phase 3 study, MELODY, applied the recommended dosing regimen.1,5
The Phase 3 MELODY trial was a randomised, placebo-controlled trial conducted across 21 countries designed to determine efficacy of nirsevimab against medically attended LRTI due to RSV confirmed by reverse transcriptase polymerase chain reaction testing through 150 days after dosing, versus placebo, in healthy late preterm and term infants (35 weeks gestational age or greater) entering their first RSV season.1,5 The primary endpoint was met, reducing the incidence of medically attended LRTI, such as bronchiolitis or pneumonia, caused by RSV by 74.5% (95% CI 49.6, 87.1; P<0.001) compared to placebo. Infants were randomised (2:1) to receive a single 50mg (in infants weighing <5kg) or 100mg (in infants weighing ≥5kg) intramuscular injection of nirsevimab or placebo. Between July 2019 and March 2020, 1,490 infants were randomised to either nirsevimab or placebo at the RSV season start.1,5 Data was published on the primary analysis in NEJM in March 2022.
Findings from nirsevimab’s clinical trial programme include a pre-specified pooled analysis of the Phase 3 MELODY trial and the recommended dose from the Phase 2b trial, in which an efficacy (relative risk reduction versus placebo) of 79.5% (95% CI 65.9, 87.7; P<0.0001) was seen against medically attended LRTI, such as bronchiolitis or pneumonia, caused by RSV in infants born at term or preterm entering their first RSV season.2 The pooled analysis studied healthy preterm and term infants who received the recommended dose of nirsevimab based on weight compared to placebo through Day 151 and showed an efficacy of 77.3% (95% CI 50.3, 89.7; P<0.001) against RSV LRTI hospitalisations, as published in NEJM in March 2022.1,2
MEDLEY was a Phase 2/3, randomised, double-blind, palivizumab-controlled trial with the primary objective of assessing safety and tolerability for nirsevimab in preterm infants and infants with congenital heart disease (CHD) and/or chronic lung disease of prematurity (CLD) eligible to receive palivizumab.10,11 Between July 2019 and May 2021, approximately 918 infants entering their first RSV season were randomised to receive a single 50mg (in infants weighing <5kg) or 100mg (in infants weighing ≥5kg) intramuscular injection of nirsevimab or palivizumab. Safety was assessed by monitoring the occurrence of treatment emergent adverse events (TEAEs) and treatment emergent serious adverse events (TESAEs) through 360 days post-dose.10,11 Serum levels of nirsevimab following dosing (on day 151) in this trial were comparable with those observed in the Phase 3 MELODY trial, indicating similar protection in this population to that in the healthy term and late preterm infants is likely.10 Data was published in NEJM in March 2022.
The results of MELODY, Phase 2/3 MEDLEY and the Phase 2b trials illustrate that nirsevimab helps protect infants during their first RSV season against RSV disease with a single dose.1,2,5,7,8,9,10,11 This all-infant population includes preterm, healthy late preterm and term infants, as well as infants with specific conditions.
These trials formed the basis of regulatory submissions that began in 2022.
About Sanofi
We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people’s lives. Our team, across some 100 countries, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the centre of our ambitions.
Sanofi Forward-Looking Statements
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References
1. Hammitt LL, MD et al. Nirsevimab for Prevention of RSV in Healthy Late -Preterm and Term Infants. N Engl J Med. 2022;386 (9): 837-846. doi: 10.1056/NEJMoa2110275.
2. Simões, E, et al. Pooled efficacy of nirsevimab against RSV lower respiratory tract infection in preterm and term infants. ESPID 2022 Congress; 2022 May 9-13. Hybrid Congress.
3. WHO Preferred Product Characteristics for Respiratory Syncytial Virus (RSV) Vaccines, WHO, Available at: WHO Preferred Product Characteristics for Respiratory Syncytial Virus (RSV) Vaccines [Accessed November 2022]
4. Wennergren, G and Kristjånsson, S. Relationship between respiratory syncytial virus bronchiolitis and future obstructive airway diseases. Eur Respir J. 2001; 18:1044–1058 DOI: 10.1183/09031936.01.00254101
5. 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 November 2022]
6. Beyfortus – Summary of Product Characteristics (SmPC) – (eMC) [Internet] Available from: https://ec.europa.eu/health/documents/community-register/2022/20221031157262/anx_157262_en.pdf [Accessed November 2022]
7. Clinicaltrials.gov. A Study to Evaluate the Safety and Efficacy of MEDI8897 for the Prevention of Medically Attended RSV LRTI in Healthy Preterm Infants. (MEDI8897 Ph2b). https://clinicaltrials.gov/ct2/show/results/NCT02878330. [Accessed November 2022]
8. Griffin P, MD et al. (2020). Single-Dose Nirsevimab for Prevention of RSV in Preterm Infants. NEJM 2020; 383: 415-425. DOI: 10.1056/NEJMoa1913556.
9. Wilkins, D, et al. Nirsevimab for the prevention of respiratory syncytial virus infection: neutralizing antibody levels following a single dose. ESPID 2022 Congress; 2022 May 9-13. Hybrid Congress.
10. Domachowske J, MD et al. Safety of Nirsevimab for RSV in Infants with Heart or Lung Disease or Prematurity. N Engl J Med. 2022; 386 (9).
11. 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 (MEDLEY). [Accessed November 2022]
12. Synagis - Summary of Product Characteristics (SmPC) - (eMC) [Internet]. Available from: https://www.ema.europa.eu/en/documents/product-information/synagis-epar-product-information_en.pdf. [Accessed November 2022]
13. Respiratory syncytial virus (RSV): symptoms, transmission, prevention, treatment guidance, UK Health Security Agency, Available at: Respiratory syncytial virus (RSV): symptoms, transmission, prevention, treatment - GOV.UK (www.gov.uk) [Accessed November 2022]
14. Verway,C, and Nunes, MC. RSV lower respiratory tract infection and lung health in the first 2 years of life. The Lancet Global Health. 2020; 8(10): E1247-E1248.
15. Oxford Vaccine Group. Respiratory syncytial virus. What is respiratory syncytial virus (RSV)? [Online] Available at: https://vk.ovg.ox.ac.uk/vk/rsv [Accessed November 2022]
16. The Impact of the respiratory syncytial virus on the NHS, Society and economy in the UK, RAND Corporation, Available at: https://www.rand.org/randeurope/research/projects/impact-of-respiratory-syncytial-virus.html [Accessed November 2022]
17. Centers for Disease Control and Prevention. Vaccines & Immunizations. August 18, 2017. https://www.cdc.gov/vaccines/vac-gen/immunity-types.htm [Accessed November 2022]