A second season of nirsevimab for respiratory syncytial virus (RSV) appeared safe and effective in children with congenital heart disease (CHD) or chronic lung disease (CLD) who were born preterm, according to study results from the Journal of the Pediatric Infectious Disease Society.

Study authors sought to evaluate the safety of nirsevimab compared with palivizumab for RSV protection in children with CHD and CLD who had received a second seasonal dosing of nirsevimab. Researchers also estimated the efficacy of the second seasonal dose of nirsevimab, using pharmacokinetic extrapolation to determine whether children reached nirsevimab serum levels adequate to protect them against RSV exposure. Researchers considered 80% of children achieving the protective serum level to be indicative of successful efficacy.

Investigators for the current study built upon the results of the phase 2/3 MEDLEY trial (ClinicalTrials.gov Identifier: NCT03959488), which evaluated the safety and efficacy of nirsevimab for RSV protection in preterm infants with CHD and CLD during their first RSV season. The 310 children enrolled in that trial were all eligible to receive palivizumab according to local or national guidelines and were randomized to receive nirsevimab (50 mg for weight less than 5kg; 100 mg for weight of 5kg or more), palivizumab (15 mg per kilogram of weight), and/or placebo.

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The current second-season analysis, conducted from July 28, 2020, to April 30, 2022, included 262 children approximately 15 to 16 months old. Of those, 252 children completed at least 150 days of follow-up after the second season. Participants in the current analysis were divided into 3 treatment groups:

  • Those who received nirsevimab prior to the first RSV season who then received nirsevimab 200 mg followed by 4 once-monthly doses of placebo in the second season (N/N, n=180).
  • Those who received palivizumab prior to the first RSV season and who then received nirsevimab 200 mg followed by 4 once-monthly doses of placebo in the second season (P/N, n=40).
  • Those who received palivizumab prior to the first RSV season and then received palivizumab intramuscularly for 5 once-monthly doses (P/P, n=42).

Investigators then assessed adverse events (AEs), anti-drug antibodies, and nirsevimab serum concentrations for children in the 3 groups through day 360 following the first dose they received for season 2. The safety analysis also assessed AEs through 30 days post first treatment dose, thus allowing investigators to compare AEs resulting from 1 dose of nirsevimab vs palivizumab.

The investigators found that the overall incidence of 1 or more serious AEs was higher among P/N and N/N groups, compared with the P/P group, respectively (10.0% vs 9.4% vs 0.0%). The researchers noted that these events were primarily due to infections or underlying comorbidities and no safety-related trends or concerns were identified. Additionally, the incidence of adverse events of grade 3 or greater severity was higher among the P/N and N/N group, compared with the P/P group, respectively (10.0% vs 7.8% vs 2.4%).

The incidence of anti-drug antibodies (ADAs) was minimal in the N/N treatment group; ADAs were detected in only 1 participant prior to the first RSV season and none after.

With respect to efficacy, the investigators found that 98% of the P/N and N/N treatment groups achieved target serum concentrations associated with efficacy.

Study limitations include small sample sizes in the P/P and P/N treatment groups and the timing of the trial, which took place during the COVID-19 pandemic and may thus have influenced results.

“In children with congenital heart disease and/or chronic lung disease, 200 mg nirsevimab administered before their second RSV season had a similar safety profile to that of palivizumab and achieved serum exposures at levels associated with efficacy in healthy infants,” the study authors concluded.

Disclosures: This study was supported by AstraZeneca and Sanofi. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Domachowske JB, Chang Y, Atanasova V, et al. Safety of re-dosing nirsevimab prior to RSV season 2 in children with heart or lung disease. Journal of the Pediatric Infectious Diseases Society. Published online July 19, 2023. doi:10.1093/jpids/piad052

This article originally appeared on Pulmonology Advisor