Moderna’s two-dose pediatric Covid-19 vaccination schedules are generally safe and effective for children ages 6 months to 17 years, the FDA said in a separate briefing document released late Friday.
Background: The documents are the result of months of reviewing the companies’ safety and immunogenicity data, which must be independently verified by federal agencies. They will form the basis for review by the FDA’s independent vaccine advisors at Tuesday and Wednesday meetings, where they will vote on whether to recommend the agency approve EUAs for the myriad age groups.
The first meeting will focus on Moderna’s proposed vaccine series for children aged 6 to 17, while the second day will cover both companies’ offers to vaccinate the country’s youngest children up to 6 months of age.
Limited efficacy data: The FDA analyzed the vaccines’ ability to induce neutralizing antibody responses in children comparable to young adults, a concept known as immune bridging. Both met the agency’s criteria for success.
Real-world efficacy against the Omicron variant in the 6-month to 5-year age group for Moderna’s vaccine ranged from 36 percent to 51 percent, but efficacy estimates for all age groups were “generally consistent” with rates observed in adult studies during the same waves of variants, the FDA said.
Preliminary analyzes of the effectiveness of the Pfizer vaccine in children under 5 years of age from 80 percent against illness, despite just 10 Covid cases being reported among study participants prior to the April data cut-off date.
There were still many unknowns about efficacy in both companies’ data, which reflects the current state of vaccination among adults in the United States, including how long it has been effective and how well the vaccine protects against how long-lasting Covid outcomes, the FDA said. Given adults’ experience of declining antibody protection, children will likely need booster doses in the future, the reviewers said.
Side effects such as headaches and fatigue were more common in teenagers than in younger children, probably because they received larger doses of the vaccine said the FDA. Fever was reported more frequently in the youngest vaccinees.
No new safety signals were discovered in the companies’ clinical trials, although they were unlikely to be large enough to detect the rarest of side effects, the FDA said.
The FDA’s review of the companies’ data comes after months of anxiety from parents, who were feeling strained by statements that Covid-19 vaccines would be available for the country’s youngest children by early 2022, only to see that move the data. The FDA called an advisory committee meeting in February to consider a two-dose primary series of Pfizer’s vaccine, only to withdraw once data suggested a third dose could boost its effectiveness.
Parents and advocates for giving children under 5 access to vaccines broke out in April over a POLITICO report that said the Biden administration is leaning towards concurrent approval of Pfizer-BioNTech and Moderna’s products to stop advertising the vaccines , a move some believed resulted in regulators sitting at Moderna’s request while Pfizer continued to collect data and complete its filing. FDA Commissioner Robert Califf later insisted there would be no raid at Moderna’s request, but the Advisory Committee meeting schedule ultimately ensured that both vaccines would be considered head-to-head.
Myocarditis shift: No cases of myocarditis or pericarditis – inflammation of the heart muscle or the lining of the heart – were reported in Moderna’s pediatric studies. Both conditions are known risks of Covid-19 messenger RNA vaccines, particularly in males aged 12 to 39.
Data from international vaccine safety surveillance programs suggests higher rates of heart disease occur after vaccination with Moderna’s vaccines than with Pfizer-BioNTechs, which, combined with the availability of Pfizer’s vaccine for adolescents, convinced the FDA last fall not to to move with an EUA then forward for 12 to 17-year-olds, the agency said in the briefing document.
But analyzes of US data in active and passive surveillance systems conducted in April and May “support no difference in myocarditis/pericarditis risk for [Moderna] compared to [Pfizer-BioNTech] or suggest a small difference due to uncertainties,” the FDA said, later calling evidence of a difference in risk between the two products “inconclusive.”
The benefit-risk balance of approving Moderna’s vaccine as an option for teenagers amid concerns about heart inflammation will likely be a major source of debate during Tuesday’s meeting.
Neither condition was reported in children under the age of 5 in the Pfizer and BioNTech studies, and the risk for this age group is unknown. The risk of vaccine-associated myocarditis for this age group may be lower compared to older teens because the rate is lower in males ages 5 to 11 and the incidence of side effects is lower in the youngest children, the FDA said.