The federal agency’s Advisory Committee on Immunization Practices (ACIP) also added the recently approved therapeutic to the Vaccines for Children program.
The CDC's ACIP voted today to recommend nirsevimab-alip (Beyfortus) for the protection against severe respiratory syncytial virus (RSV) in the first respiratory virus season for all infants and for a second season for those who remain at increased risk for severe RSV.
Specifically, the ACIP committee voted on the following questions:
The increased risk categories include the following characteristics:
The committee voted unanimously in favor for both questions, and today's actions provide clinicians with some guidance to decide if their youngest patients need to receive nirsevimab in a second respiratory season.
“This represents a paradigm change. For the first time since the discovery of RSV we have a strategy to prevent RSV in all infants during their first respiratory season—first exposure to the virus, when young infants are at the highest risk to develop severe disease and being hospitalized,” Octavio Ramilo, MD, chair, Department of Infectious Diseases, St. Jude Children’s Research Hospital said in an interview with Contagion. “As clinicians we are very encouraged with the data derived from clinical trials as this mAb is very effective and safe. For the families, we can finally offer them an effective strategy to protect the most vulnerable young children.”
Nirsevimab is a long-acting antibody, which is manufactured by Sanofi and AstraZeneca. Back in mid-July, the FDA approved it for the prevention of RSV lower respiratory tract disease (LRTD) in newborns and infants born during or entering their first RSV season, and for children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season.
During today’s meeting, ACIP discussed having nirsevimab being administered under the federal agency’s Vaccines for Children (VFC) program. According to the CDC, “the VFC program is a federally funded program that provides vaccines at no cost to children who might not otherwise be vaccinated because of inability to pay.” One meeting commentator made note of her concerns about the potential inequities in both rural and urban areas and the possible limitations in receiving nirsevimab.
On this subject, the committee voted on the following question:
1. Approve the Vaccines for Children resolution for nirsevimab for RSV?
On this vote, the committee voted unanimously in favor of approval. The adoption of nirsevimab into the VFC program should help alleviate some of the access issues, and Ramilo said the inclusion of it into the program is a significant milestone.
“RSV is the single most frequent cause of hospitalization in the US during the first year of life. And it causes significant morbidity beyond hospitalization,” Ramilo said. “It is the most common cause of pneumonia in infants, many ED and clinic visits and facilitates major complications such as bacterial superinfection like pneumonia and otitis and long-term pulmonary sequelae such as wheezing. So, we need to prevent RSV infections in all infants, and for that reason to reach all infants it was critical that it got included in the Vaccines for Children program.”
A ”Passive Immunization Product”
One of the challenges that was pointed out during today’s meeting was that nirsevimab is classified as a therapeutic as opposed to a vaccine, explained CDC Director of the Immunization Services Division (ISD) Georgina Peacock, MD, MPH. Therefore, it might cause some confusion in the public and the antibody will not have reported adverse events like vaccines currently do. Despite this, CDC plans to monitor nirsevimab throughout the respiratory virus season.
As nirsevimab is a monoclonal antibody, one of the commentators made the distinction that nirsevimab is a “passive immunization product.” Sanofi previously stated that nirsevimab does "not require the activation of the immune system to help offer timely, rapid, and direct protection against the disease.”
The MELODY Trial Results
The phase 3 MELODY trial (Trial 04) was a randomized, double-blind, placebo-controlled trial conducted across 21 countries designed to determine the safety and efficacy of nirsevimab against medically attended LRTD caused by RSV in healthy term and late preterm infants (35 weeks gestational age or greater) entering their first RSV season, including efficacy against severe disease such as hospitalization, through 150 days after dosing. The primary endpoint was met, reducing the incidence of medically attended RSV LRTD by 74.9% (95% CI 50.6, 87.3; P<0.001) compared to placebo. The efficacy of nirsevimab against the secondary endpoint of hospitalization was 60.2% (95% CI: -14.6, 86.2).
As previously reported in Contagion, additional trial data came from the HARMONIE phase 3b study. This trial recruited more than 8000 infants under 12 months of age across Germany, France, and the United Kingdom. The investigators compared a single intramuscular dose of nirsevimab (<5 kg 50 mg; ≥5 kg 100 mg) to no intervention, and found nirsevimab reduced hospitalizations due to severe RSV-related LRTD by 83.21%.
Additional data from the HARMONIE trial suggest nirsevimab reduced the incidence of hospitalizations due to severe RSV-related LRTD, defined by requiring oxygen supplementation, by 75.71%. Nirsevimab also reduced all-cause LRTD hospitalization by 58.04% compared to infants who received no intervention. Throughout the HARMONIE trial, and into the 12-month follow-up period, nirsevimab maintained a favorable safety profile.
Sanofi and AstraZeneca plan to make the monoclonal antibody available in the United States ahead of the upcoming 2023-2024 RSV season.
“Beyfortus is the only monoclonal antibody approved for passive immunization to provide safe and effective protection for all infants during their first RSV season,” Thomas Triomphe, executive vice president, Vaccines, Sanofi, said in a previous statement. “I am proud that, by prioritizing this potential game-changer, we are now about to bring Beyfortus to American families.”