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Federal advisers to the US Food and Drug Administration (FDA) voted unanimously today to recommend the use of the Moderna and Pfizer-BioNTech COVID-19 vaccines in infants and young children.
The Vaccines and Related Biological Products Advisory Committee (VRBPAC) of the FDA voted 21-0 to say that benefits of a two-dose series of Moderna’s mRNA vaccine outweigh risk for use in infants and children 6 months through 5 years of age.
The panel then voted 21-0 to say that benefits of a three-dose series of the Pfizer-BioNTech mRNA vaccine outweigh risk for use in infants and children 6 months through 4 years of age.
The FDA is not bound to follow the suggestions of its advisory committees, but it often does. Moderna and Pfizer are seeking to expand emergency use authorization (EUA) for their vaccines. EUAs are special clearances used to allow use of products in connection with public health crises such as the pandemic.
The Pfizer vaccine has standard, nonemergency FDA approval for use in people 16 years of age and older. The FDA also has granted EUA clearance for use of the shot in people ages 5 to 15.
The VRBPAC on Tuesday recommended granting EUA clearance for Moderna”s COVID-19 vaccine for people ages 6 to 17. The Moderna vaccine already has full approval for use in people 18 years of age and older.
Many parents have been waiting for a clearance of COVID vaccines for their infants and young children, seeking protection for them at a time of continued spread of the virus.
The White House on June 9 outlined plans for making 10 million doses of COVID vaccines available for children under the age of 5 in the coming weeks.
The Centers for Disease Control and Prevention (CDC) has scheduled a June 18 meeting of its Advisory Committee on Immunization Practices, where members of that panel will vote on recommendations about use of the Moderna and Pfizer-BioNTech vaccines in infants and young children. The last step in the approval process to get shots into arms will be endorsement by the CDC director if the committee votes in favor of the vaccines .
For and Against
During the public session during Wednesday’s FDA meeting, speakers offered varied opinions.
Some urged the panel to vote against the EUA expansion, citing concerns about risks of COVID vaccines in general.
But at the close of the meeting, top FDA vaccine official Peter Marks, MD, PhD, urged the public to be cautious about drawing conclusions from reading incident reports of side effects.
He said he has seen a “Twitter storm” during the day about claims of side effects. but stressed that the FDA has reported to the public on the rare side effects linked to the COVID vaccines, such as myocarditis, with advisories based on a review of reports of side effects. But many of these reports, gathered from the Vaccine Adverse Event Reporting System (VAERS) system, will turn out on further inspection not to be related to vaccination.
Many other speakers urged members of the panel to support expanded use of the vaccines for infants and young children. These speakers emphasized how lack of a vaccine to date has isolated young children who remain unprotected, even with about 83% of those age 5 and older in the US having received at least one COVID shot.
Marks noted that there have been 442 deaths from COVID among children under 4 years of age during the pandemic, a number that he compared with the 78 deaths reported in the H1N1 flu. He urged the panel “to be careful that we don’t become numb to the number of pediatric deaths because of the overwhelming number of older deaths here.”
Panelist H. Cody Meissner, MD, a pediatric infectious disease specialist from Tufts University, said the vaccine should be made available — particularly for children considered to be at high risk for complications from COVID –but health officials need to present a clear picture of the relatively low risks to children of harm from the vaccines– and from COVID.
“That has to be communicated clearly to parents so that they can participate in the decision about vaccinating a child in this age group,” Meissner said.
The results presented Wednesday from studies of the shots in younger children were less impressive than those from the initial COVID vaccine trials done in adults. This was not a surprise to panelists given the rise of the omicron variant and the evolution of the pandemic, but it still led to comments about the need for further continued study of the vaccines in young children even if they are authorized.
Consider that in 2020, Pfizer won the first EUA for a COVID vaccine of any kind with data that pegged the shot’s efficacy rate at 95%. Statisticians estimated a likely possible range, or 95% confidence interval, for the vaccine efficacy rate at 90.3% to 97.6%.
Those estimates were based on finding eight cases of COVID reported among 18,198 study participants who got the Pfizer-BioNTech shot, compared with 162 cases among the 18,325 people in the placebo group, according to the FDA review of Pifzer’s initial application.
But on Wednesday, FDA advisers had to consider an EUA application for which the data did not make as strong a case for the vaccine’s benefit among younger patients.
Pfizer presented what the FDA called a “preliminary descriptive analysis” of vaccine efficacy among participants in Study C4591007 who received three study vaccinations, following accrual of 10 total confirmed COVID-19 cases occurring at least 7 days after the third dose.
Looking at results for study participants ages 6 to 23 months of age, there was one case in the group that got the Pfizer-BioNTech shot and two in the placebo group, pegged as a 75.6% vaccine efficacy rate — but one with caveats to the small numbers of cases. The 95% confidence interval for this vaccine efficacy rate was reported as-369.1% to 99.6% according to the FDA staff review.
For participants 2-4 years of age with and without evidence of prior SARS-CoV-
2 infection, there were two cases in the group that got the shot and five in the placebo group showing a vaccine efficacy rate of 82.4%, with a 95% confidence interval estimated ranging between -7.6% and 98.3%. For the combined analysis of both age groups, the efficacy rate was estimated at 80.4%, with a 95% confidence interval of 14.1% and 96.7%.
Doran Fink, MD, PhD, a top official in the FDA’s vaccines division, noted that the current EUA application for expanded pediatric use involved “some very preliminary” results that involved “a small number of cases and limited follow up time.”
But he stressed that the evidence gathered to date for the Pifzer application for use of its COVID shot in infants and young children met the threshold for conditional clearance during a crisis.
“We do feel very confident that the evidentiary standard for benefit for an EUA has been met here,” but added that more data would be needed to address questions about the efficacy of the vaccine beyond a third dose and whether an additional dose may be needed.
Pfizer also used a comparison known as “immunobridging” in support of the application. This looked at SARS- CoV-2 50% neutralizing antibody titers for the children in the age group covered by the EUA application and compared them to a randomly selected subset of 16-25-year-old participants in another study,
Key data for the pending Moderna EUA for use of its shot in infants and young children came from study P204. In it, Moderna found 51 cases of COVID among 1511 children ages 6 months to 23 months who got the vaccines, versus 34 cases among 513 children who received a placebo, according to an FDA staff review.
That resulted in a vaccine efficacy rate pegged at 50.6%, with a 95% confidence interval of 21.4% to 68.6%.
Looking at the children ages 2 to 5 years in the P204 study, there were 119 cases out of 2594 participants who got the shot, versus 61 cases of 858 in the placebo arm, or 7.1%. That translated to a 36.8% vaccine efficacy rate, with a confidence interval 12.5% to 54.0%.
Panelist Jay Portnoy, MD, of Children’s Mercy Hospital in Kansas City said all of the pediatricians he knows are waiting for the FDA to authorize the new uses of these vaccines in infants and young children.
“The death rate from COVID in young children may not be extremely high, but it’s absolutely terrifying to parents to have their child be sick, have to go to the hospital or even go to the emergency room or their primary care doctor because they’re sick and having trouble breathing,” said Portnoy, who served as the panel’s consumer representative.
Kerry Dooley Young is a freelance journalist based in Washington, DC. She is the core topic leader on patient safety issues for the Association of Health Care Journalists. Young earlier covered health policy and the federal budget for Congressional Quarterly/CQ Roll Call and the pharmaceutical industry and the Food and Drug Administration for Bloomberg. Follow her on Twitter at @kdooleyyoung.