Nirsevimab for Prevention of Hospitalizations Due to RSV in Infants

Drysdale, Simon B. Ph.D., F.R.C.P.C.H.
Cathie, Katrina M.D., F.R.C.P.C.H.
Flamein, Florence M.D., Ph.D.
Knuf, Markus Ph.D.
Collins, Andrea M. M.D., Ph.D.
Hill, Helen C. Ph.D.
Kaiser, Friedrich M.D.
Cohen, Robert M.D.
Pinquier, Didier M.D.
Felter, Christian T. M.D.
Vassilouthis, Natalya C. M.D.
Jin, Jing Ph.D.
Bangert, Mathieu Ph.D.
Mari, Karine M.Sc.
Nteene, Rapi M.D.
Wague, Sophie M.Sc.
Roberts, Michelle M.D.
Tissières, Pierre M.D., D.Sc.
Royal, Simon M.P.H., M.R.C.G.P.
Faust, Saul N. Ph.D., F.R.C.P.C.H.

From the Centre for Neonatal and Paediatric Infections, St. George's, University of London, and the Department of Paediatrics, St. George's University Hospitals National Health Service (NHS) Foundation Trust, London (S.B.D.), the National Institute for Health Research Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, and the Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton (K.C., S.N.F.), the Liverpool Vaccine Group, Liverpool School of Tropical Medicine (A.M.C., H.C.H.), and Liverpool University Hospitals Foundation, NHS Trust (A.M.C.), Liverpool, Sanofi, Reading (C.T.F., N.C.V.), and the University of Nottingham Health Service, University of Nottingham, Nottingham (S.R.) — all in the United Kingdom; Université de Lille, INSERM, Centre Hospitalier Universitaire (CHU) de Lille, CIC-1403 INSERM-CHU, Lille (F.F.), the French Clinical Research Infrastructure Network-PEDSTART, Tours (F.F.), Centre Hospitalier Intercommunal de Créteil, and Association Clinique et Thérapeutique Infantile du Val-de-Marne, Créteil (R.C.), CHU Rouen, Department of Neonatal Pediatrics and Intensive Care and Neuropediatrics, Charles Nicolle University Hospital, Rouen (D.P.), Sanofi Vaccines, Lyon (M.B., R.N., S.W.), Sanofi Vaccines, Marcy L'Etoile (K.M.), Pediatric Intensive Care, Neonatal Medicine and Pediatric Emergency Department, Assistance Publique-Hôpitaux de Paris, Paris-Saclay University, Bicêtre Hospital, Le Kremlin-Bicêtre (P.T.), and the Institute of Integrative Biology of the Cell, Centre National de la Recherche Scientifique, Commissariat à l'Energie Atomique, Paris-Saclay University, Gif sur Yvette (P.T.) — all in France; Children's Hospital, Worms (M.K.), Pediatric Infectious Diseases, University Medicine, Mainz (M.K.), and Gemeinschaftspraxis für Kinder und Jugendmedizin, Tangstedter Landstrasse 77, Hamburg (F.K.) — all in Germany; Sanofi, Huipu Mansion, Beijing (J.J.); and Sanofi Vaccines, Bridgewater, NJ (M.R.).

Prof. Faust can be contacted at [email protected] or at the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, or the Faculty of Medicine and Institute for Life Sciences, University of Southampton, Tremona Road, Southampton, SO16 6YD, United Kingdom.

A list of the investigators in the HARMONIE Study Group is provided in the Supplementary Appendix, available at NEJM.org.

Drs. Drysdale, Cathie, Flamein, Knuf, and Collins and Dr. Tissières, Dr. Royal, and Prof. Faust contributed equally to this article.

A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.

Supported by Sanofi, and AstraZeneca,

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

New England Journal of Medicine 389(26):p 2425-2435, December 28, 2023. | DOI: 10.1056/NEJMoa2309189

Abstract

Background

The safety of the monoclonal antibody nirsevimab and the effect of nirsevimab on hospitalizations for respiratory syncytial virus (RSV)-associated lower respiratory tract infection when administered in healthy infants are unclear.

Methods

In a pragmatic trial, we randomly assigned, in a 1:1 ratio, infants who were 12 months of age or younger, had been born at a gestational age of at least 29 weeks, and were entering their first RSV season in France, Germany, or the United Kingdom to receive either a single intramuscular injection of nirsevimab or standard care (no intervention) before or during the RSV season. The primary end point was hospitalization for RSV-associated lower respiratory tract infection, defined as hospital admission and an RSV-positive test result. A key secondary end point was very severe RSV-associated lower respiratory tract infection, defined as hospitalization for RSV-associated lower respiratory tract infection with an oxygen saturation of less than 90% and the need for supplemental oxygen.

Results

A total of 8058 infants were randomly assigned to receive nirsevimab (4037 infants) or standard care (4021 infants). Eleven infants (0.3%) in the nirsevimab group and 60 (1.5%) in the standard-care group were hospitalized for RSV-associated lower respiratory tract infection, which corresponded to a nirsevimab efficacy of 83.2% (95% confidence interval [CI], 67.8 to 92.0; P<0.001). Very severe RSV-associated lower respiratory tract infection occurred in 5 infants (0.1%) in the nirsevimab group and in 19 (0.5%) in the standard-care group, which represented a nirsevimab efficacy of 75.7% (95% CI, 32.8 to 92.9; P=0.004). The efficacy of nirsevimab against hospitalization for RSV-associated lower respiratory tract infection was 89.6% (adjusted 95% CI, 58.8 to 98.7; multiplicity-adjusted P<0.001) in France, 74.2% (adjusted 95% CI, 27.9 to 92.5; multiplicity-adjusted P=0.006) in Germany, and 83.4% (adjusted 95% CI, 34.3 to 97.6; multiplicity-adjusted P=0.003) in the United Kingdom. Treatment-related adverse events occurred in 86 infants (2.1%) in the nirsevimab group.

Conclusions

Nirsevimab protected infants against hospitalization for RSV-associated lower respiratory tract infection and against very severe RSV-associated lower respiratory tract infection in conditions that approximated real-world settings. (Funded by Sanofi and AstraZeneca; HARMONIE ClinicalTrials.gov number, NCT05437510).

Nirsevimab for Prevention of RSV Hospitalization in Infants

Nirsevimab, a monoclonal antibody targeting RSV, led to decreased hospitalizations for RSV-associated lower respiratory tract infection in infants during their first RSV season, in an open-label, pragmatic trial.