Evolving Strategies for RSV Prevention in Infants

Respiratory syncytial virus (RSV) remains a leading cause of lower respiratory tract infection in infants worldwide, accounting for significant morbidity and hospitalizations each year.¹ For over 2 decades, prevention strategies have been limited to palivizumab (Synagis; MedImmune), a monoclonal antibody FDA approved for the prevention of serious RSV infection in certain high-risk infants and which requires monthly intramuscular dosing during RSV season for sustained protection.²

However, in recent years, the landscape of RSV prevention has changed significantly. The FDA approval of nirsevimab (Beyfortus; AstraZeneca/Sanofi) in 2023 and clesrovimab (Enflonsia; Merck) in 2025 has expanded the opportunity to receive a preventative agent to nearly all infants, a feat which can be accomplished in both cases with a single dose per RSV season. The approval of these 2 new monoclonal antibody agents led to major updates in CDC and American Academy of Pediatrics (AAP) recommendations. Following these changes, the manufacturer of palivizumab (Sobi) announced the voluntary market withdrawal of palivizumab at the end of this calendar year.³

In light of all these recent changes, this article reviews how RSV prevention has evolved, highlights key clinical trial data for nirsevimab and clesrovimab, and summarizes the latest CDC and AAP recommendations for the prevention of severe RSV infection in infants in the US.

From Palivizumab to Next-Generation Monoclonal Antibodies

Palivizumab, approved in 1998, was a groundbreaking intervention for high-risk populations, namely premature infants going into their first RSV season and those with congenital heart or chronic lung disease entering their second RSV season. Despite demonstrated efficacy in reducing RSV-related hospitalizations, its requirement for up to five monthly doses and high-cost limited use.²

Now, newly approved next-generation monoclonal antibodies offer season-long protection with just a single intramuscular dose and expand eligibility beyond high-risk groups, making it accessible on an indication basis to nearly all infants entering their first RSV season.

Nirsevimab (Beyfortus) Clinical Evidence

Nirsevimab is a long-acting monoclonal antibody targeting the RSV fusion (F) protein. The phase 2b/3 MELODY trial conducted in healthy, term infants born at or after 35 weeks gestational age demonstrated a 74.5% reduction in medically attended RSV-associated lower respiratory tract infections and a 62.1% reduction in RSV-related hospitalizations compared with placebo.⁴ To evaluate the use of nirsevimab in high-risk infants who would historically qualify for palivizumab administration, the phase 2/3 MEDLEY trial was conducted in preterm infants (born at < 35 weeks gestational age) and infants with chronic lung disease (CLD) or uncorrected congenital heart disease (CHD). The MEDLEY trial confirmed a favorable safety profile in these high-risk infants, demonstrating similar rates of adverse events compared to palivizumab.⁵

Clinical Role

The approval of nirsevimab in 2023 expanded preventative therapy eligibility to all infants younger than 8 months entering their first RSV season, as well as certain high-risk children up to 19 months of age entering their second season.³ With the single-dose regimen, completing prophylaxis is much easier for families and clinicians.

Clesrovimab (Enflonsia) Clinical Evidence

Clesrovimab, approved in 2025, is another long-acting monoclonal antibody targeting the RSV F protein. Early-phase studies have demonstrated good tolerability and robust pharmacokinetics supporting once-per-season dosing.⁶ The CLEVER trial, a phase 2B/3A trial that included early and moderate preterm infants (≥ 29 to < 35 weeks gestational age) as well as term infants (≥ 35 weeks gestation), demonstrated significant reductions in RSV-associated illness (60.5% reduction) and hospitalizations (84.3% reduction), consistent with findings from nirsevimab trials.⁷ Of note, the CLEVER trial only included infants entering their first RSV season. At this time, clesrovimab has not been studied in infants entering their second RSV season.

Clinical Role

Unlike nirsevimab, Clesrovimab uses a fixed 105 mg dose for all infants regardless of weight. With its approval, providers now have 2 effective prophylactic options to choose from for infants entering their first RSV season, which may help mitigate supply shortages. Importantly, the launch of clesrovimab coincided with the voluntary withdrawal of palivizumab, making nirsevimab and clesrovimab the primary options available moving forward.

Updated CDC and AAP Recommendations in 2025

As of 2025, the CDC and AAP recommend the following^3,8:

• Infants younger than 8 months born during or entering their first RSV season: a single dose of either nirsevimab or clesrovimab.

• Children aged 8 through 19 months at increased risk for severe RSV disease (e.g., severe prematurity, chronic lung disease, congenital heart disease, immunocompromise) entering their second RSV season: a single dose of nirsevimab

For infants entering their first RSV season, nirsevimab and clesrovimab are considered interchangeable, with selection often guided by product availability and institutional formulary preference. Until palivizumab is fully removed from market at the end of the year, palivizumab can be considered as an alternative when nirsevimab and clesrovimab are not available.

Practical Considerations for Pharmacists

Pharmacists play a key role in ensuring successful implementation of these updated recommendations. Key considerations include:

• Education: Counsel caregivers on the role of monoclonal antibodies in the prevention of severe RSV infections and the importance of timely administration before or during RSV season
• Access and Supply: Monitor institutional formularies and supply chain to ensure product availability
• Safety Monitoring: Safety profiles for these agents are overall favorable, but monitor for injection-site reactions (uncommon, mild) and anaphylaxis (rare, serious) ^4,6

Conclusion

With nirsevimab and clesrovimab now available, RSV prevention looks very different than it did a few years ago. Moving from monthly palivizumab to a single seasonal dose is a big step forward for families and clinicians. For pharmacists, staying current with these updates is essential to guide providers and families as we enter an RSV season with an entirely new standard of care.

Abbreviations: LRTI, lower respiratory tract infection; IM, intramuscular; PI, prescribing information.

REFERENCES

1. Shi T, McAllister DA, O’Brien KL, 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(10098):946-958. doi:10.1016/S0140-6736(17)30938-8

2. MedImmune, LLC. Synagis (palivizumab) Prescribing Information. 2017. Accessed August 28, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/103770s5185lbl.pdf

3. Centers for Disease Control and Prevention. RSV immunization guidance for infants and young children. Updated August 2025. Accessed August 28, 2025. https://www.cdc.gov/rsv/hcp/vaccine-clinical-guidance/infants-young-children.html

4. Hammitt LL, Dagan R, Yuan Y, 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

5. Griffin MP, Yuan Y, Takas T, et al. Safety and efficacy of nirsevimab for RSV in infants with heart or lung disease or prematurity. N Engl J Med. 2022;386(9):892-894. doi:10.1056/NEJMc2112186

6. Griffin MP, Kargiannakis T, Li F, et al. Safety and pharmacokinetics of clesrovimab in healthy infants: a phase 1b/2a study. J Infect Dis. 2024;229(12):2013-2022. doi:10.1093/infdis/jiaa543

7. Merck & Co, Inc. Clesrovimab (Enflonsia) healthcare provider information. Accessed August 28, 2025. https://www.merckvaccines.com/enflonsia/

8. American Academy of Pediatrics. Updated recommendations for prevention of RSV in infants and young children. 2025.