The monoclonal antibody nirsevimab (Beyfortus) reduced hospitalizations among infants with respiratory syncytial virus (RSV)-associated lower respiratory tract infection, the randomized, pragmatic HARMONIE trial showed.
In over 8,000 infants included in the study, 0.3% who received nirsevimab were hospitalized for RSV-associated lower respiratory tract infection compared with 1.5% of those who received standard care, which corresponded to a nirsevimab efficacy rate of 83.2% (P<0.001), reported Saul Faust, PhD, of University Hospital Southampton in England, and colleagues in the New England Journal of Medicine.
“We now have a way of preventing 80% of [infant] admissions due to RSV,” Faust told MedPage Today.
Very severe RSV-associated lower respiratory tract infection — defined as hospitalization with an oxygen saturation of less than 90% and a need for supplemental oxygen — occurred in 0.1% of infants in the nirsevimab group compared with 0.5% in the standard-care group, which represented a nirsevimab efficacy of 75.7% (P=0.004).
“These latest results show that this long-acting antibody is safe and could protect thousands of babies from hospitalization when used in conditions similar to routine clinical practice,” Faust said in a press release.
Unlike previous clinical trials, “the trial settings included maternity wards, community pediatrician offices, and general practices,” the authors wrote.
The study only looked at infants hospitalized for RSV-associated lower respiratory tract infection and not those hospitalized for other reasons potentially related to RSV infection, such as dehydration.
“For more than 50 years, our options to prevent RSV disease have been largely ineffective or, as with the previous and current RSV prophylaxis products, have been limited to selected high-risk populations,” wrote Natasha Halasa, MD, MPH, of Vanderbilt University Medical Center in Nashville, Tennessee, in an accompanying editorial. “The introduction of nirsevimab brings a wave of excitement because it offers a more practical, single-dose alternative to previous interventions and extends protection to all infants.”
Nirsevimab first gained FDA approval to prevent RSV-related lower respiratory tract infections in infants and very young children in July. The antibody has the potential to provide protection to all infants if it is administered in a program similar to routine vaccine strategies, Faust and team noted. Maternal vaccination, FDA-approved in August, is another option to prevent RSV in neonates and infants.
In the U.S., nirsevimab is in short supply for the 2023-2024 RSV season. The CDC issued a health advisory in October, recommending that nirsevimab be prioritized for infants at highest risk for severe RSV infections. Prefilled syringes of the 100-mg dose are especially in short supply.
“Nirsevimab comes with new challenges alongside its benefits,” Halasa wrote, pointing out that the vast majority of RSV lower respiratory tract infections and associated deaths occur in low- to middle-income countries. “Ensuring that nirsevimab reaches these vulnerable populations is not only a matter of equity but also imperative to mitigate the global effects of RSV on health and society,” she stressed.
The HARMONIE trial enrolled infants 12 months or younger in France, Germany, and the U.K., who were entering their first RSV season. Faust and team randomized 4,037 infants (mean age 4.5 months, 51.7% boys) to receive a single intramuscular injection of nirsevimab (50 mg for infants less than 5 kg; 100 mg for those weighing 5 kg and up) and 4,021 (mean age 4.5 months, 52.4% boys) to receive no intervention before or during the 2022-2023 RSV season. Over half (51%) of the infants were enrolled in the U.K., 27% were enrolled in France, and 22% in Germany.
Infants who developed lower respiratory tract infection and were then admitted to a hospital underwent testing for RSV. To avoid bias, treating physicians did not know a patient’s RSV status before hospital admission.
The efficacy of nirsevimab against hospitalization for RSV-associated lower respiratory tract infection was similar across the three countries.
Approximately 2% of infants receiving nirsevimab experienced treatment-related adverse events. Four infants had drug reactions reported as fever, rash, and/or dermatitis. One infant developed infantile spasms 23 days after nirsevimab treatment; the investigators could not exclude nirsevimab as the cause.
The study was supported by grants from Sanofi and AstraZeneca.
Faust reported consulting for or receiving grants from AstraZeneca, GlaxoSmithKline, Janssen Pharmaceuticals, MedImmune, Merck, Novavax, Pfizer, Pfizer UK, Sanofi, Seqirus, and Valneva Austria GmbH. Other study authors also reported ties to industry.
Halasa reported receiving grants from Sanofi, Quidel, and Merck.
New England Journal of Medicine
Source Reference: Drysdale SB, et al “Nirsevimab for prevention of hospitalizations due to RSV in infants” N Engl J Med 2023; DOI: 10.1056/NEJMoa2309189.
New England Journal of Medicine
Source Reference: Halasa NB “RSV prevention — breakthroughs and challenges” N Engl J Med 2023; DOI: 10.1056/NEJMe2312934.