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Healthy infants who received a single prophylactic nirsevimab injection leading up to the respiratory syncytial virus (RSV) season were protected from RSV-related lower respiratory tract infections needing medical care, a randomized trial found.

In the phase III study, 1.2% of late-term or term infants assigned to nirsevimab required medical attention for an RSV-related lower respiratory tract infection through 150 days, as compared to 5% of those assigned to placebo, reported Tonya Villafana, PhD, of AstraZeneca in Gaithersburg, Maryland, and researchers for the MELODY study group.

This difference translated to an efficacy of 74.5% (95% CI 49.6-87.1, P<0.001) for nirsevimab, a recombinant IgG1 kappa monoclonal antibody targeting the RSV fusion protein, the group wrote in the .

For the secondary endpoint of hospitalization within 150 days for an RSV-related lower respiratory infection, the relative benefit with nirsevimab appeared similar, though not statistically significant so, at 0.6% versus 1.6% with placebo, for an efficacy of 62.1% (95% CI -8.6 to 86.8, P=0.07). However, a prespecified analysis that pooled data from the current trial and a on nirsevimab in preterm infants showed an efficacy of 77.3% against hospitalization (95% CI 50.3-89.7, P<0.001).

"Despite respiratory syncytial virus being the leading cause of pneumonia and bronchiolitis in the first year of life, there is no routine preventative option currently approved for all infants," coauthor William Muller, PhD, of Northwestern University Feinberg School of Medicine in Chicago, said in a press release.

"These exciting trial data demonstrate the potential for nirsevimab to change the prevention landscape not only by providing protection to a broad population of infants across the full respiratory syncytial virus season, but also by achieving this with a single dose," added Muller.

In a number-needed-to-treat analysis, 12 healthy infants would need to receive nirsevimab to prevent one medically attended RSV-related lower respiratory infection, and 53 would need treatment to prevent one RSV-related hospitalization.

Pre-term infants and those with underlying heart and lung disease remain at greatest risk for severe RSV, but healthy infants born at term make up the bulk of RSV-related hospitalizations. Nirsevimab, which has an extended half-life (mean 59.3 days) acts as a vaccine surrogate and has shown superior RSV inhibition to palivizumab, an FDA approved therapy for children at high risk of RSV disease.

From 2019 to 2020, the researchers randomized 1,490 healthy infants 2:1 across 21 countries to receive either a single intramuscular injection of nirsevimab (50 mg dose for those <5 kg and 100 mg for those ≥5 kg) or placebo, prior to the RSV season.

The study included infants born at a minimum gestational age of 35 weeks and who were up to 1 year of age (58% were 3 months or younger at baseline). RSV infections were confirmed by central laboratory testing.

About half of the infants were white, 52% were boys, and 60% weighed 5 kg or more. Most were born at term (86%). Only 0.3% of infants had serious diseases at study entry -- one with cystic fibrosis and three with Down syndrome.

Through day 361, more antidrug antibodies were detected in the nirsevimab group (6.1% vs 1.1% in the placebo group). "Antidrug antibodies tended to develop later and did not affect nirsevimab pharmacokinetics over the RSV season; however, their influence on subsequent administration is unknown," the researchers noted.

The types of adverse events (AEs) were similar between groups, the researchers reported, and nirsevimab was associated with fewer serious AEs (6.8% vs 7.3% with placebo). There was one case of grade 3 generalized macular rash considered related to nirsevimab. Three of the 994 infants assigned to the nirsevimab group died during the study -- one from failure to thrive and two from gastroenteritis -- but these were deemed unrelated to the intervention.

The authors acknowledged several limitations to the data, including disruptions in RSV circulation in South Africa due to lockdowns related to the COVID-19 pandemic, as well as disruptions in trial enrollment, potentially underpowering the findings. Additionally, a lower efficacy was reported among those ages 3 months or younger (58% of the study population) and those weighing under 5 kg (40% of the population).

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