In July 2020, Griffin et al. (1) reported in The New England Journal of Medicine on the use of nirsevimab, a monoclonal antibody with an extended half-life, against respiratory syncytial virus (RSV) to prevent RSV infection. After a single dose, patients had fewer RSV lower respiratory tract infections (LRTI) requiring medical attention and fewer hospitalizations for RSV through the next 150 days than with placebo. The study included healthy infants < 1 year of age, born between 29 weeks 0 days and 34 weeks 6 days at the start of their first RSV season, and who did not meet the American Academy of Pediatrics (AAP) guidelines to receive RSV prophylaxis (2). The incidence of medically attended RSV LRTI was 70.1% lower in those receiving nirsevimab than placebo; incidence of hospitalization was 78.4% lower. Nirsevimab had a favorable safety profile.
More recently, Hammitt et al. published the results of a phase 3 randomized clinical trial of nirsevimab. This study examined the same endpoints as the Griffin trial but was conducted in infants > 35 weeks gestation (3). The results were consistent with the Griffin trial with respect to lower medically attended LRTI in the nirsevimab group and maintenance of nirsevimab levels through 150 days. No reported significant adverse events or deaths were attributed to nirsevimab or placebo. This trial found a relatively lower efficacy of nirsevimab among infants who were < 3 months of age or who weighed < 5 kg at the injection time.
Every winter, primary care offices and hospitals are overwhelmed by infants coughing and wheezing with RSV, the leading cause of LRTI in infants < 1 year of age, with the sickest being those < 35 weeks gestation, those with chronic lung disease of prematurity (CLDP), and those with congenital heart disease (CHD).
In the US, palivizumab, a monoclonal antibody administered monthly during RSV season, is the only immunoprophylaxis approved by the Food and Drug Administration (FDA) for severe RSV LRTI in infants born < 35 weeks’ gestation and those with CLDP or hemodynamically significant CHD. In 2014, the AAP updated their recommendations on the use of palivizumab, restricting the target population to infants born at < 29 weeks and children with CHD or CLDP given high cost, limited benefit from palivizumab prophylaxis, and lower community burden of disease (2).
Since publication of the revised AAP guidelines, reports have multiplied of increased hospitalization and severity of illness in infants with RSV and decreased use of palivizumab even in populations for which the AAP still recommends its use (4,5). Given this increased burden of RSV disease, in 2018, the National Perinatal Association published separate guidelines for palivizumab use, which are closer to the original FDA indications for use (6).
Nirsevimab’s first regulatory body review is currently underway with the European Medicines Agency with further global regulatory submissions planned in 2022. The availability of a safe, effective, cost-effective alternative to palivizumab that can be administered as a single dose and that provides protection for an entire RSV season would be a welcome intervention for vulnerable infants and those caring for them. We eagerly await results of these reviews.