The infection rate was 1.2% among the 994 infants assigned to the nirsevimab group versus 5.0% of the 496 babies given placebo before the start of the RSV season (P<0.001), researchers report in the New England Journal of Medicine.
The research team estimated that 55.8 cases of medically attended RSV-associated lower-respiratory-tract infections could be prevented for every 1,000 infants treated.
The treatment was not able to significantly reduce the risk of hospitalization for an RSV-associated lung infection. The rates were 0.6% in the monoclonal antibody group versus 1.6% with placebo (P=0.07).
But coauthor Dr. Tonya Villafana, global vaccines franchise chief at AstraZeneca, said the study "was not powered for that secondary endpoint."
"The study began when the COVID pandemic hit, so we didn't enroll the full number when we did the primary efficacy analysis," Dr. Villafana said. "With the COVID pandemic, kids were being kept out of the hospital. The trend is there and we were close on it."
AstraZeneca and Sanofi, which financed the study, announced topline results on April 26, saying that nirsevimab had reduced medically attended RSV infections in the children, but offering no details. The companies did not mention hospitalization rates.
RSV is the leading cause of hospitalizations for healthy infants born at term. It sends 57,000 infants and young children into the hospital annually, and kills an estimated 94,600 to 149,400 children under 5 worldwide each year.
"We shouldn't lose sight of how major this result is for the field," Dr. Villafana told Reuters Health by phone. "People have been trying to develop vaccines for RSV for over 60 years and there hasn't been a study until now that's given us a positive readout in this population. So that is a significant result we have not seen before. We now have an intervention we can use for all infants, not just the highest-risk preterm infant population."
In 2020, researchers reported that nirsevimab was able to lower the infection risk by 70.1% among healthy preterm babies and cut the odds of hospitalization for RSV by 42.5% in that group.
MELODY was an attempt to see if the benefit would be just as great - and the treatment just as safe - among children who had not celebrated their first birthday at the start of the RSV season and were born at a gestational age of at least 35 weeks.
Children eligible to receive palivizumab - licensed for infants at the highest risk for severe RSV disease - were excluded.
Enrollment was done at 160 sites in 21 countries. Median age at enrollment was 2.6 months. The children were followed for 150 days after their injection.
Youngsters are continuing to be enrolled as part of the safety study, but initial findings from the trial show that the rate of side effects was no higher among babies who received the drug.
"Adverse events of grade 3 or higher severity were reported in 36 of the 987 infants (3.6%) who received nirsevimab and in 21 of the 491 infants (4.3%) who received placebo," the team reports.
Three infants, all nirsevimab recipients, died.
"None of the serious adverse events, including the deaths, were considered by the investigators to be related to nirsevimab or placebo," the researchers said. "An adverse event thought to be related to nirsevimab or placebo occurred in 1% of infants."
Although the treatment didn't produce a statistically significant reduction in the rate of hospitalization for RSV-associated lower-respiratory-tract infection, the researchers say nirsevimab had an efficacy of 59% when it came to preventing any RSV-associated respiratory illness.
They also note that when 2020 results from the preterm infants were folded into the new data, the drug prevented 77% of hospitalizations (P<0.001).
"Relatively lower estimates of efficacy were observed among infants who were younger (<=3.0 months vs. >3.0 months of age) and weighed less (<5 kg vs. >=5 kg)," they reported.
In a separate report in the journal, the researchers behind the 2020 study report that the safety profile of nirsevimab appears similar to palivizumab among preterm infants and babies born with congenital heart disease and chronic lung disease.
In the preterm cohort, at least one serious adverse event was seen in 5.3% of the 206 palivizumab recipients versus 6.9% of the 406 infants given nirsevimab. Among the babies with heart or lung disease, the rates were 20.4% for 98 palivizumab recipients and 19.2% for the 208 treated with nirsevimab.
On Monday, GlaxoSmithKline announced that it had halted enrolment and vaccination in three trials of its experimental RSV vaccine designated AReSVi 006, all involving pregnant women, because of potential unspecified safety issues.
Two weeks ago, the New England Journal of Medicine reported that Enanta Pharmaceutical's experimental oral RSV therapy EDP-938 was able to bring down viral load, reduce symptoms scores and generate less mucus than placebo therapy in a phase-2a challenge study of 178 adults.
Nirsevimab works by preventing the virus from entering cells. EDP-938 acts as a replication inhibitor against RSV and early research has suggested that it can work even after the virus has infected a cell.
SOURCE: https://bit.ly/3K27mO6 and https://bit.ly/3IqUSz3 The New England Journal of Medicine, online March 2, 2022.
By Gene Emery
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