A phase 3 trial showed that nirsevimab was effective in preventing respiratory syncytial virus (RSV)-associated lower respiratory tract infection in healthy late-preterm and term infants.
Nirsevimab was found to prevent respiratory syncytial virus (RSV)-associated lower respiratory tract infection in healthy late-preterm and term infants when administered before the RSV season, according to research published in The New England Journal of Medicine.
Nirsevimab is a monoclonal antibody against RSV and has an extended half-life. While its efficacy against lower respiratory tract infection caused by RSV has been known for healthy preterm infants—born at a gestational age between 29 and 35 weeks—this phase 3 trial measured nirsevimab’s efficacy and safety in late-preterm and term infants entering their first RSV season.1
The randomized trial included 1490 infants who were born at a gestational age of at least 35 weeks, aged 1 year or younger at inclusion, and entering their first RSV season. In a 2:1 ratio, 994 infants received nirsevimab and 496 received placebo.
Infants in the nirsevimab group weighing less than 5kg received a 50mg dose, and infants weighing at least 5kg received a 100mg dose.
The population consisted of mostly (86.0%) healthy infants born at term and the median age was 2.6 months, with ages ranging from 0.03 to 11.10 months. The authors noted that 1 infant had cystic fibrosis and 3 infants had Down syndrome. Baseline characteristics were similar among both groups and this infant population was representative of the global RSV patient population.
A total of 1465 (98.3%) infants completed 150 days of follow-up, with 1367 (91.7%) completing 360 days of follow-up.
Twelve (1.2%) infants in the nirsevimab group and 25 (5%) infants in the placebo group experienced a medically attended RSV-associated lower respiratory tract infection, with the authors measuring an efficacy of 74.5% for nirsevimab (95% CI, 49.6-87.1; P < .001).
Additionally, 6 (0.6%) infants in the former group and 8 (1.6%) infants in the latter group were hospitalized for RSV-associated lower respiratory tract infection through 150 after injection. Taking this into account, the authors found nirsevimab to be 62.1% effective against hospitalization for RSV-associated lower respiratory tract infection (95% CI, −8.6-86.8; P = .07).
An adverse event thought to be related to either nirsevimab or placebo occurred in 1% of infants. The authors did not identify any safety concerns. However, they did find relatively lower efficacy among infants aged 3 months or younger weighing less than 5 kg at time of injection, saying it was potentially related to the small sample size and overlapping confidence intervals.
“Because body weight correlates with age, it is also possible that shared factors may explain the lower observed efficacy among these infants,” the authors explained. “Although there was a tendency for higher mean serum nirsevimab levels among infants who received 100 mg, there was a large overlap in serum levels with infants who received 50 mg.”
Of the infants with data available up to day 361 of follow-up, antidrug antibodies were detected after baseline in 58 of 951 (6.1%) infants receiving nirsevimab, and in 5 of 473 (1.1%) infants receiving placebo. Serious adverse events were reported in 67 of 987 (6.8%) infants in the former group and in 36 of 491 (7.3%) infants in the latter group.
While overall RSV incidence was within the expected range in the northern hemisphere during the 2019-2020 RSV season, the COVID-19 pandemic and subsequent lockdowns played a major role in the “abrupt termination of RSV circulation” in the southern hemisphere, specifically South Africa, according to the authors.
“Given that the target enrollment was not reached, the trial had less power than originally planned to evaluate the efficacy of nirsevimab with respect to preventing hospitalizations or the difference in efficacy in subgroups,” they said.
In a separate, ongoing phase 2/3 trial, researchers are also evaluating the safety and pharmacokinetics of nirsevimab in infants at risk for severe RSV-associated lower respiratory infection who are eligible to receive palivizumab. In the same issue of the journal, another team reported on the safety and pharmacokinetics in this population.2
This trial includes infants born preterm with congenital heart disease (CHD) or chronic lung disease (CLD), compared with infants with uncorrected, partially corrected, or medically treated CHD or CLD who needed treatment for CHD or CLD within 6 months. Overall, 310 were enrolled in the CHD–CLD cohort and 615 in the preterm cohort.
So far, the researchers found, at day 151, serum levels of nirsevimab were similar in both cohorts, and the antidrug antibody response was low. The safety profile of nirsevimab was similar to that of palivizumab in infants with CHD or CLD and in infants born preterm, they said.
1. Hammitt LL, Dagan R, Yuan Y, et al. Nirsevimab for prevention of RSV in healthy late-preterm and term infants. N Engl J Med. Published online March 2, 2022. doi:10.1056/NEJMoa2110275
2. Domachowske J,Madhi SA, Simões EAF, et al. Safety of nirsevimab for RSV in infants with heart or lung disease or prematurity. N Engl J Med. Published online March 2, 2022. doi:0.1056/NEJMc2112186