Real-World Study Finds Beyfortus Is Highly Effective against Hospitalization for RSV-Associated Bronchiolitis in Infants

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis, which accounted for nearly one-fifth of all pediatric hospitalizations in the U.S. before the pandemic.

Beyfortus (nirsevimab) the year-old monoclonal antibody injection against lung disease caused by respiratory syncytial virus, was 83% effective at preventing hospitalization due to RSV-associated bronchiolitis in infants, a real-world study found. It also was effective, although to a lesser extent, against worse outcomes.

The findings were published July 10 in the New England Journal of Medicine.

RSV is the leading cause of bronchiolitis and pneumonia in children under 12 months. It is estimated to be responsible for more than 33 million lower respiratory tract infections a year worldwide in children under 5, along with 3.2 million hospitalizations and 100,000 deaths.

As opposed to bronchitis, which affects the larger airways (bronchi) in the lung and is more common in older children and adults, bronchiolitis affects the smaller airways (bronchioles) and is most common in babies and children under 2. It causes the bronchioles to swell and fill with mucus, making it hard to breathe.

Although bronchiolitis is often mild and can be treated at home, the condition accounted for 18% of all pediatric hospitalizations in the U.S. before the pandemic, when only one therapy was available, with very limited eligibility, and required monthly injections.

That changed in July 2023, when Beyfortus was approved by the FDAand then recommended for newborns and babies under 1 year born during or entering their first RSV season (typically October through April). It also was recommended for children up to 24 months who remain at risk of severe RSV disease through their second season.

Beyfortus, marketed by Sanofi, is not a vaccine; it does not work by provoking an immune system response. As a Johns Hopkins explanation about Beyfortus says, the immune system does not “learn” from Beyfortus. Rather, the monoclonal antibody fends off infection more or less directly without recruiting the immune system into the process. Beyfortus supplies what is sometimes referred to as “passive immunity.”

Beyfortus is administered as a single intramuscular injection for infants (two for older children), provides protection almost immediately but lasts for a far shorter period than most vaccines. It essentially is good for one RSV season.

Based on clinical studies showing that it was very effective against RSV-associated lower respiratory tract infection leading to medical care in infants, the European Medicines Agency approved it in November 2022. In France, national guidelines recommended free injections of a single dose for all children, although a shortage led authorities to prioritize newborns or very young infants.

The Beyfortus program began in metropolitan France on Sept. 15, 2023, creating the conditions for research that could measure whether the injection's effectiveness against hospitalization in the real world supported the pre-market findings. (Maternal vaccines against infant RSV were not yet available in France.)

Corresponding author Naïm Ouldali, M.D., Ph.D., a professor in the Department of General Pediatrics, Pediatric Infectious Disease, and Internal Medicine at Robert Debré University Hospital in Paris, along with Camille Bréhin, M.D., Ph.D., in the General Pediatrics Department at Toulouse University Hospital’s Children’s Hospital, Toulouse, France, decided on a prospective, matched case-control study at six tertiary hospitals (including four with pediatric intensive care units) across metropolitan France. There were more than 30 co-authors.

Starting with all infants younger than 12 months who were hospitalized for RSV-associated bronchiolitis between Oct. 15 and Dec. 10, 2023, the researchers ended up with 690 case patients, nearly 9% of whom received nirsevimab at least seven days before the hospital visit. They were matched with 345 controls, of whom a larger percentage had previously received the injection, who were hospitalized for a variety of conditions excluding lower respiratory tract infections.

Overall, the study found, nirsevimab was 83% effective at preventing hospitalization for RSV-associated bronchiolitis. A subgroup analysis showed no significant differences across age groups.

Nirsevimab was 69.6% effective against patients going to pediatric intensive care units, and 67.2% effective against requiring ventilator support.

The observational case-control design of the study cannot show causation, but the findings were similar to — even slightly better than — the results of the three clinical trials that led regulators to approve the shot. The authors speculated that the difference might be because the premarket studies had later endpoints, so the monoclonal antibody product’s effectiveness may have waned.