Phase IIIb HARMONIE data demonstrated Beyfortus reduced the incidence of
hospitalisations due to RSV by 83%
Late-breaking data are being presented at the European Society for Paediatric
Infectious Diseases meeting
New data from the Beyfortus (nirsevimab) Phase IIIb HARMONIE trial demonstrated an 83.2% (95% CI 67.8 to 92.0; P<0.001) reduction in hospitalisations due to respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) in infants under 12 months of age during the RSV season, compared to those who received no RSV intervention (11/4,037 vs 60/4,021). The results also demonstrated a 75.7% (95% CI 32.8 to 92.9; P<0.001) reduction in very severe RSV LRTI hospitalisations in infants under 12 months, compared to those who received no RSV intervention (5/4,037 vs 19/4,021).1 Throughout HARMONIE, Beyfortus maintained a favourable safety profile, in keeping with the pivotal trial results. Beyfortus has been developed jointly by AstraZeneca and Sanofi.
These data are being presented at the 41st Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID) from 8-12 May 2023 in Lisbon, Portugal and complement previous data published in The New England Journal of Medicine demonstrating efficacy of Beyfortus in protection against RSV-related LRTI hospitalisations.2
Dr Simon Drysdale, Consultant Paediatrician in Infectious Diseases at St. George’s University Hospital NHS Foundation Trust and Co-Chief Investigator of HARMONIE, said: “RSV-related chest infections lead to high numbers of infants under 12 months old being hospitalised every year. These data reinforce the potential public health benefit of nirsevimab in terms of helping to reduce the strain on hospitals caused each year by RSV.”
Iskra Reic, Executive Vice President, Vaccines and Immune Therapies, AstraZeneca, said: “These new data reinforce our belief that Beyfortus has the potential to transform the medical community’s approach to preventing RSV infections in infants and alleviate the physical and emotional burden that RSV can place on families and healthcare services.”
AstraZeneca also presented additional safety and efficacy data at the Congress:
- A comprehensive summary of all safety data from the pivotal trials of nirsevimab in healthy infants (≥29 weeks gestational age (wGA)) reinforce the acceptable safety profile of nirsevimab, through 360 days post-dose. There were no AEs of special interest reported except for non-serious cutaneous hypersensitivity reactions in six nirsevimab recipients (0.2%).3
- Pooled data from the Phase IIb trial (infants ≥29 to <35 wGA) and Phase III MELODY trial full enrolment cohort (infants ≥35 wGA) demonstrated an efficacy of 79% (95% confidence interval [CI] 68.5, 86.1) against medically attended (MA) RSV lower respiratory tract infection (LRTI). These data reinforce nirsevimab’s consistency across endpoints and studies with approximately 70-80% efficacy against medically attended RSV LRTI vs placebo with a single dose.4
- New analysis of the Phase III MELODY trial shows a similar incidence of non-RSV respiratory viruses between nirsevimab and placebo participants, which suggests that there is no replacement of RSV with other viruses following nirsevimab administration.5
Notes
RSV
RSV is the most common cause of lower respiratory infections, including bronchiolitis and pneumonia in infants.6 It is also a leading cause of hospitalisation in all infants.7-10 Globally, in 2019, there were approximately 33 million cases of acute lower respiratory infections leading to more than three million hospitalisations, and it was estimated that there were 26,300 in-hospital deaths of children younger than five years.11 RSV-related direct medical costs, globally – including hospital, outpatient and follow-up care – were estimated at €4.82 billion in 2017.12
HARMONIE
The Hospitalised RSV Monoclonal Antibody Prevention (HARMONIE) study is a large European interventional randomised, open-label clinical trial aiming to determine the efficacy and safety of a single intramuscular (IM) dose of Beyfortus (<5 kg 50 mg; ≥5 kg 100 mg), compared to no intervention (standard of care), for the prevention of hospitalisations due to RSV-related LRTI in infants under 12 months of age. The trial is open at more than 250 sites, supported by National Institute of Health Research infrastructure (UK), the PEDSTART network (France) and NETSTAP e.V.(Germany) and has recruited over 8000 infants, 4037 in nirsevimab group and 4021 in the no intervention group. The primary efficacy data for HARMONIE were collected in the 2022-2023 RSV season and the trial is due to complete in June 2024.1
Beyfortus (nirsevimab)
Beyfortus is a single dose long-acting antibody, developed and commercialised in partnership by AstraZeneca and Sanofi using AstraZeneca’s YTE technology. Beyfortus has been developed to offer newborns and infants direct RSV protection via an antibody to help prevent medically attended lower respiratory tract infections caused by RSV. Monoclonal antibodies do not require the activation of the immune system to help offer timely, rapid and direct protection against disease.13
In November 2022, Beyfortus was approved by the European Commission and by the UK Medicines and Healthcare products Regulatory Agency (MHRA),14 and is currently undergoing regulatory review in the US.
Beyfortus has been granted regulatory and other designations to facilitate expedited development by several major 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 (PRIME) scheme; and named “a medicine for prioritized development” under the Project for Drug Selection to Promote New Drug Development in Pediatrics by the Japan Agency for Medical Research and Development (AMED).
Sanofi Alliance
In March 2017, AstraZeneca and Sanofi announced an agreement to develop and commercialise nirsevimab. Under the terms of the agreement, AstraZeneca leads development and manufacturing activities, and Sanofi leads commercialisation activities and records revenue. The two companies share costs and profits in all territories except in the US. Revenue from the agreement is reported as Alliance Revenue and Collaboration Revenue in the Company’s financial statements. Following a revision to the profit-sharing arrangement relating to the development and commercialisation of nirsevimab in the US between AstraZeneca, Sanofi and Sobi, Sobi has entered into a direct relationship with Sanofi, replacing the previous participation agreement with AstraZeneca entered into in November 2018.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
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References
1. Drysdale et al. Efficacy of nirsevimab against RSV lower respiratory tract infection hospitalization in infants: preliminary data from the HARMONIE phase 3b trial. Presented at 41st Annual Meeting of the European Society for Paediatric Infectious Diseases in Lisbon.
2. Hammitt et al. Nirsevimab for Prevention of RSV in Healthy Late-Preterm and Term Infants. N Engl J Med 2022; 386:837-846 DOI: 10.1056/NEJMoa2110275
3. Mankad et al. Comprehensive summary of all safety data of nirsevimab in healthy infants: experience to date from pivotal trials. Presented at 41st Annual Meeting of the European Society for Paediatric Infectious Diseases in Lisbon.
4. Madhi et al. Nirsevimab efficacy against RSV lower respiratory tract infection in preterm and term infants by subtype: pooled analysis of phase 2b and phase 3 melody trials. Presented at 41st Annual Meeting of the European Society for Paediatric Infectious Diseases in Lisbon.
5. Aksyuk A., Nirsevimab immunisation did not alter the distribution of non-RSV viruses relative to placebo in a pivotal Phase 3 clinical study (MELODY). Presented at 41st Annual Meeting of the European Society for Paediatric Infectious Diseases in Lisbon.
6. R K. Respiratory Syncytial Virus Vaccines. Plotkin SA, Orenstein WA, Offitt PA, Edwards KM, eds Plotkin’s Vaccines 7th ed Philadelphia. 2018;7th ed. Philadelphia:943-9.
7. Leader S, Kohlhase K. Respiratory syncytial virus-coded pediatric hospitalizations, 1997 to 1999. The Pediatric infectious disease journal. 2002;21(7):629-32.
8. McLaurin KK, Farr AM, Wade SW, Diakun DR, Stewart DL. Respiratory syncytial virus hospitalization outcomes and costs of full-term and preterm infants. Journal of Perinatology: official journal of the California Perinatal Association. 2016;36(11):990-6.
9. Rha B, et al. Respiratory Syncytial Virus-Associated Hospitalizations Among Young Children: 2015-2016. Pediatrics. 2020;146:e20193611.
10. Arriola CS, et al. Estimated Burden of Community-Onset Respiratory Syncytial Virus-Associated Hospitalizations Among Children Aged <2 Years in the United States, 2014-15. J Pediatric Infect Dis Soc. 2020;9:587-595
11. Li Y, et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis. Lancet 2022;399:92047–64.
12. Zhang S, et al. Cost of Respiratory Syncytial Virus-Associated Acute Lower Respiratory Infection Management in Young Children at the Regional and Global Level: A Systematic Review and Meta-Analysis. J Infect Dis. 2020;222(Suppl 7):S680-687.
13. Centers for Disease Control and Prevention. Vaccines & Immunizations. August 18, 2017. https://www.cdc.gov/vaccines/vac-gen/immunity-types.htm. Accessed May 2023
14. Precision vaccinations. Beyfortus (Nirsevimab) RSV Antibody 2023. https://www.precisionvaccinations.com/vaccines/beyfortus-nirsevimab-rsv-antibody-2023#:~:text=November%204%2C%202022%20%2D%20AstraZeneca%20and,during%20their%20first%20RSV%20season. Accessed May 2023