Nirsevimab for prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants

Approved indication: prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants born during or entering their first RSV season, and children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season
Beyfortus (Sanofi-Aventis)
prefilled syringe containing 50 mg/0.5 mL or 100 mg/1.0 mL solution for intramuscular injection

Respiratory syncytial virus (RSV) causes infection in most children by 2 years of age, often presenting as bronchiolitis with breathing difficulty. During the first 6 months of life, RSV infection can be severe, and children in this age group have the highest rate of hospitalisation compared with all other age groups, including adults.¹ Conditions that increase the risk of severe disease include congenital heart disease, chronic lung disease, neurological conditions that impair respiratory function, cystic fibrosis, Down syndrome, immunocompromised states and prematurity.^1,2

Nirsevimab is an injectable, long-acting monoclonal antibody that protects against RSV disease for at least 5 months after a single dose, which is usually enough for an entire RSV season. It is an alternative to palivizumab, a short-acting RSV monoclonal antibody that requires monthly injections to provide continuous protection throughout the RSV season. RSV monoclonal antibodies provide passive immunisation and work immediately after injection. RSV is neutralised when the monoclonal antibody binds to the RSV fusion protein.

The MELODY trial (n=3012 participants) compared nirsevimab with placebo in healthy infants born at a gestational age of 35 weeks or more who were entering their first RSV season.³ Nirsevimab reduced the incidence of RSV-associated lower respiratory tract disease (LRTD) requiring medical attention by 76.4% (1.2% incidence in the nirsevimab group compared with 5.4% in the placebo group), and RSV-associated hospitalisation by 76.8% (0.4% compared with 2.0%), over a 5-month period.³

Efficacy was similar in a clinical trial with 1453 preterm infants (29 to less than 35 weeks gestational age); medically attended RSV-associated LRTD was 70.1% lower in infants who received nirsevimab compared with those who received placebo prior to their first RSV season, and hospitalisation for RSV-associated LRTD was 78.4% lower.⁴

Both of the above-mentioned placebo-controlled trials included infants from the northern and southern hemispheres.^3,4 In a pragmatic randomised open-label study of more than 8000 healthy infants born at more than 29 weeks gestational age in the northern hemisphere, nirsevimab was compared with standard care (no preventive intervention); the incidence of RSV-associated hospitalisation for LRTD was 83.2% lower in the nirsevimab group (0.3% compared with 1.5%).⁵

The frequency of adverse events in clinical trials was similar among recipients of nirsevimab and placebo, and no serious adverse events were considered to be related to nirsevimab.¹ There may be a small risk of severe hypersensitivity reactions including anaphylaxis after receiving nirsevimab, so recipients should be monitored for 15 minutes after administration.¹

Nirsevimab can be given at birth to infants born during or entering their first RSV season. For infants born after the RSV season, administration may be delayed until just before the next RSV season unless there is risk of out-of-season infection. Nirsevimab is administered as a single intramuscular injection at a dose of 50 mg for infants less than 5 kg and 100 mg for infants 5 kg or more.

Infants up to 24 months of age with conditions that increase the risk of severe RSV disease may also benefit from a dose of nirsevimab at the start of their second RSV season. The recommended dosage in this case is 200 mg, administered as two 100 mg injections at the same visit.

Nirsevimab can be co-administered with other routine childhood vaccines. Since it provides passive immunisation through an RSV-specific monoclonal antibody, nirsevimab is not expected to interfere with the active immune response to co-administered vaccines.¹

Nirsevimab provides a new option for prevention of severe RSV disease and hospitalisation in infants.^* At the time of writing, nirsevimab is not available on the National Immunisation Program or listed on the Pharmaceutical Benefits Scheme. Some Australian jurisdictions have introduced funded RSV immunisation programs using nirsevimab.¹ The Australian Technical Advisory Group on Immunisation (ATAGI) anticipates that the supply of nirsevimab will be limited in coming months and recommends prioritising infants at highest risk of severe disease.¹

* An alternative to passive immunisation of the infant using an RSV monoclonal antibody is to active vaccination of the mother during pregnancy using an RSV vaccine that has been approved for use in pregnant women; maternal vaccination provides protection to the infant through the transfer of antibodies to the baby in utero.¹ There is currently one RSV vaccine registered for use during pregnancy in Australia (Abrysvo), but at the time of writing it has not yet been marketed.

This new drug comment was finalised on 23 May 2024.

🅃 manufacturer provided the AusPAR and the product information. The Transparency Score is explained in New drugs: transparency, Vol 37 No 1, Aust Prescr 2014;37:27.

At the time the comment was prepared, information about this drug was available on the websites of the Food and Drug Administration in the USA, the European Medicines Agency and the Therapeutic Goods Administration.

 

References

1. Australian Technical Advisory Group on Immunisation. Statement on the use of nirsevimab for prevention of severe disease due to respiratory syncytial virus (RSV) in infants. Department of Health and Aged Care; 2024. [cited 2024 May 14]
2. Therapeutic Goods Administration. Australian Public Assessment Report for Beyfortus. Department of Health and Aged Care; 2024.
3. Muller WJ, Madhi SA, Seoane Nunez B, Baca Cots M, Bosheva M, Dagan R, et al. Nirsevimab for Prevention of RSV in term and late-preterm infants. N Engl J Med 2023;388:1533-4.
4. Griffin MP, Yuan Y, Takas T, Domachowske JB, Madhi SA, Manzoni P, et al. Single-dose nirsevimab for prevention of RSV in preterm infants. N Engl J Med 2020;383:415-25.
5. Drysdale SB, Cathie K, Flamein F, Knuf M, Collins AM, Hill HC, et al. Nirsevimab for prevention of hospitalizations due to RSV in infants. N Engl J Med 2023;389:2425-35.

 

The new drug commentaries in Australian Prescriber are prepared by the editors and reviewed by the Editorial Advisory Committee. Some of the views expressed on newly approved products should be regarded as preliminary, as there may be limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Advisory Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.