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If the debate has been heated over vaccines for adults and on the need for extra booster shots, FDA and its expert advisors will face even more scrutiny over the safety and value of vaccinating children under age 12. This population generally has had much lower COVID-19 infection rates than adults, but hospitalizations now have increased dramatically with the spread of the Delta variant, plus the return to school and other activities. The rise in pediatric COVID cases has alarmed the medical community, yet widespread vaccine hesitancy among many parents will make it critical to present strong safety results to gain broad protection for children.
The issue has moved to center stage as Pfizer/BioNTech announced plans to seek FDA approval this month of a smaller dose of its Comirnaty vaccine for children ages 5-11, as well as similar approval from the European Medicines Agency and other regulatory authorities. As Pfizer did in expanding use of its vaccine to younger adolescents, the company will file an emergency use application (EUA) with FDA, based on results from a Phase II/III study of a two-dose regimen on over 4000 participants aged 6 months to 11 years.1 The study shows, according to Pfizer, that a lower 10-microgram shot for the 5-to-11 age group, one-third the dose for adults and adolescents, provides a sufficiently robust neutralizing antibody response, while also supporting safety and tolerability in these young subjects.
The clinical trial also enrolled similar numbers of younger children ages 6 months to 5 years and hopes to provide topline readouts for this group by year-end. Children under age 5 received a lower 3 microgram dose for each of two injections, and results will be evaluated for two age cohorts, children 2-5 years of age and those 6 months to 2 years old.
This initial Pfizer/BioNTech statement did not present specific study data, but sponsor said it will submit its research results for publication in a scientific peer-reviewed journal, while also preparing its filing for FDA. The announcement specified that clinical trials in multiple regions enrolled 2,268 children ages 5-11, with one-third receiving placebo. However, due to the generally lower infection rate among youngsters, there were too few numbers of ill participants to determine higher protection from the vaccine vs. placebo; that conclusion is based on a comparison of higher immune response levels in vaccinated vs. unvaccinated study participants.
The sponsor also notes that the lower dose for children can be linked to fewer side effects. In an early study that administered higher doses to young participants, adverse events were higher, although still comparable to older patients. But those children who received the lower dose experienced fewer incidences of fever, headache and fatigue, while also showing a strong antibody response. Even after increasing the size of the pediatric trial at FDA’s request, Pfizer found no cases of heart inflammation or other serious side effects that have occurred after vaccination with some older individuals, although the sponsors continue to monitor study participants for ongoing effects.
FDA staff will review the Pfizer data closely following its submission and is expected to ask its Vaccine and Related Biological Products Advisory Committee (VRPBAC) to weigh the results and make recommendations. If approved, the Advisory Committee on Immunization Policy (ACIP) at the Centers for Disease Control and Prevention (CDC) then will propose a specific vaccination schedule.
In response to earlier pressure from some quarters for FDA to quickly authorize preventives for younger children, agency leaders explained the need for very careful scientific evaluation to ensure that any vaccines for children are safe, as well as effective. FDA acting commissioner Janet Woodcock and Peter Marks, director of the Center for Biologics Evaluation and Research (CBER), penned a statement in early September emphasizing that FDA “will follow the science” to fully assess the safety of current vaccines. Woodcock and Marks also warned parents not to pressure pediatricians to provide their children with a vaccine approved for adults and adolescents:as far as vaccines go, children are not just young adults.2