A new monoclonal antibody to protect infants and high-risk toddlers from respiratory syncytial virus (RSV) is expected to be available this fall, following Thursday’s approval by the Centers for Disease Control and Prevention (CDC) director.
The approval came shortly after the CDC’s Advisory Committee on Immunization Practices (ACIP) provided an enthusiastic recommendation while acknowledging there are logistical hurdles like cost to overcome.
“This is a spectacular advancement. It’s going to help families and offices keep kids out of the hospital,” said ACIP member Jamie Loehr, M.D., FAAFP, a family physician. “ … There will be growing pains, but I don’t want to lose sight of how important this advancement is.”
ACIP voted 10-0 Thursday to recommend nirsevimab for infants younger than 8 months born during or entering their first RSV season and certain high-risk children ages 8-19 months entering their second season.
The AAP will review ACIP’s guidance and provide its own additional guidance in the near future.
“We’re very excited about the potential to prevent so much of these hospitalizations,” said Sean T. O’Leary, M.D., M.P.H., FAAP, chair of the AAP Committee on Infectious Diseases. “… We’ll be working on our communications as well as helping to craft implementation guidance for our partners with equity as a very clear focus.”
Nirsevimab (Beyfortus) was developed by AstraZeneca in partnership with Sanofi. The product is a form of passive immunization intended to protect children against lower respiratory tract disease caused by RSV. It was approved by the Food and Drug Administration (FDA) in mid-July.
RSV causes about 58,000 to 80,000 hospitalizations and 100 to 300 deaths per year in children under 5 years, according to CDC data. No vaccines are licensed in the U.S. to prevent RSV in children. Another monoclonal antibody, palivizumab, is available only for certain high-risk infants and young children and requires monthly injections during the RSV season.
When pooling data from phase 2b and 3 trials of infants, nirsevimab was found to be 79% effective in reducing the risk of medically attended lower respiratory tract infection caused by RSV. Efficacy was about 81% against hospitalization, according to the CDC. The product is expected to provide protection for at least 150 days.
In high-risk children, trial populations were not large enough to determine efficacy, so investigators established efficacy by extrapolating data from term and preterm infants in the previously mentioned trials.
The most commonly reported adverse reactions in infants were injection site reactions and rash.
Nirsevimab is given as an intramuscular injection with a prefilled syringe. It will be given as a single dose to infants under 8 months entering their first RSV season (October-March). Those born shortly before or during the season should get it in their first week of life. Those with a prolonged hospital stay should get it shortly before or promptly after discharge.
The dosage is 50 milligrams (mg) for children weighing less than 5 kilograms (kg) and 100 mg for children weighing 5 kg and above.
In tropical climates and Alaska where the RSV season may be different than the rest of the U.S., clinicians should consult state, local or territorial guidance on timing.
High-risk children ages 8-19 months also will be eligible for a 200 mg dose just before their second RSV season. The eligibility criteria include children the AAP recommends for palivizumab — children with chronic lung disease of prematurity who require medical support during the six months before the start of their second RSV season, children with severe immunocompromise and children with cystic fibrosis who have manifestations of severe lung disease or weight-for-length less than the 10th percentile. American Indian and Alaska Native (AI/AN) children also will be eligible as studies have shown they may have increased rates of RSV-associated hospitalization and difficulty accessing care from remote locations.
Palivizumab should not be given to infants who have already received nirsevimab in the same season, per the FDA approval. Children who received palivizumab in their first season, can get nirsevimab in their second season if they meet the eligibility criteria.
Nirsevimab can be co-administered with other age-appropriate vaccines. Adverse events when giving nirsevimab alone should be reported to the FDA’s MedWatch Adverse Event Reporting Program. If an adverse event occurs while co-administering nirsevimab with a vaccine, it should be reported to the Vaccine Adverse Event Reporting System.
Logistics of implementation
ACIP members praised nirsevimab for the protection it will provide, but acknowledged the rollout will be challenging.
Nirsevimab will be covered by insurance as well as through the Vaccines for Children (VFC) program, which covers immunizations for children who are Medicaid-eligible, uninsured, underinsured or AI/AN. It is expected to cost $495 in the private sector and $395 in the VFC program. However, only 10% of birthing hospitals participate in the program, and participants must carry both VFC and private stock. It is unclear whether nirsevimab will be included in bundled payments for newborn care and if so, how long that will take.
In outpatient settings, insurance payments for new products historically lag, so pediatricians will have to make an initial investment without knowing how much demand there will be for nirsevimab.
Current Procedural Terminology drug/therapeutic administration codes do not cover counseling families nor the full administrative work for a product such as nirsevimab, and nirsevimab is not eligible for stand-alone counseling. The CDC said efforts are underway to propose a unique code for nirsevimab. An American Medical Association leader at the meeting said she would bring the committee’s concerns to her group.
ACIP member Katherine A. Poehling, M.D., M.P.H., FAAP, professor of pediatrics and epidemiology and prevention at the Wake Forest University School of Medicine in North Carolina, said the issue of cost is “something that’s been weighing on me hard.”
The studies have been expensive, and companies need to be compensated for their work, she said. “But I am worried about equity, and I’m worried about hospitals saying, "We have one week to do this. Let’s make sure private practices give it rather than giving it in hospitals.'”
In recent months, concerns also have been raised about what types of medical professionals would be allowed to administer a monoclonal antibody. The CDC assuaged some of those fears Thursday, saying most states allow medical assistants to give the injection.
Other implementation hurdles center on recordkeeping. It may be challenging to enter nirsevimab into immunization information systems since it is classified as a drug. Meanwhile, the CDC stressed the importance of hospitals communicating with pediatricians and other outpatient providers, so it is clear which infants received a dose in the hospital.
Earlier this week, AAP President Sandy L. Chung, M.D., FAAP, sent a letter to the leaders of the CDC and Centers for Medicare & Medicaid Services outlining these and other logistical concerns. She urged a comprehensive strategy to ensure equitable access to the product in hospitals, birthing centers and ambulatory practice settings as well as flexibilities in the VFC program to address these and other hurdles.
“While this product holds great promise against RSV, all children are not going to be able to equitably benefit unless our federal leaders offer strategic solutions to help,” Dr. Chung said.
Another product to protect infants from RSV also is making its way through the regulatory process. In May, an FDA advisory committee voted in favor of RSVpreF, a vaccine that would be given to pregnant women. However, several committee members were concerned about preterm births. Approval of the vaccine is pending. Health officials have said most infants likely would not need protection from both RSVpreF and nirsevimab.
- CDC presentation on clinical considerations for nirsevimab
- CDC presentation on implementation considerations for nirsevimab
- AAP policy Updated Guidance for Palivizumab Prophylaxis Among Infants and Young Children at Increased Risk of Hospitalization for Respiratory Syncytial Virus Infection
- Information from the AAP Red Book on RSV
- Information for clinicians from the CDC on RSV
- Information for parents from HealthyChildren.org on RSV symptoms and when to call a doctor