FDA panel backs lower-dose Comirnaty in young children

An FDA advisory committee on Tuesday voted 17-0 with one abstention that the benefits of Pfizer/BioNTech's COVID-19 vaccine Comirnaty outweigh its risks for use in children ages five to 11 years old. The vote comes a few days after the companies reported study data demonstrating that two weaker doses of the mRNA-based vaccine was 90.7% effective at preventing symptomatic disease in this age group.

The panel endorsement will now be considered by the FDA, which could issue a final decision within days. There have been questions regarding the need and safety of vaccinating younger children against COVID-19, particularly over concerns about a potential risk of myocarditis with mRNA shots. However, in briefing documents released last week in preparation for the AdCom meeting, FDA reviewers concluded that, while the benefits of vaccination in young children depend on the incidence of COVID-19, they "clearly outweigh" risks of vaccine-associated myocarditis.

Participants in Pfizer/BioNTech's paediatric trial received two 10-μg doses of Comirnaty three weeks apart, with each shot containing one-third the dosage used for adolescents and adults. The smaller dosage was "carefully selected as the preferred dose for safety, tolerability and immunogenicity in children five to 11 years of age," the companies have said, noting that side effects for children are "generally comparable to those observed in participants 16 to 25 years of age."

Concerns over vaccine mandates

Peter Marks, director of the FDA's Center for Biologics Evaluation and Research, said prior to the vote that the AdCom "discussion is going to be about the scientific data that are presented, and it's not about vaccine mandates, which are left to other entities outside of FDA." Still, several panel members raised concerns that recommending Comirnaty to younger children might eventually lead to vaccine mandates for them.

Throughout the meeting, AdCom members weighed the risk of myocarditis against the potential for complications from COVID-19, including hospitalisations and death. Panelist Patrick Moore noted that there have been 94 children in the US who have died from the infection. Moore also pointed out that the risk of myocarditis in this younger age group is theoretical, and has been extrapolated from results in older children and young adults who have received a full-size dose of Comirnaty.

Meanwhile, despite the positive vote, several members on the FDA's panel indicated that they were less confident in saying every child should get the vaccine, or if it should only be recommended for those at high-risk of severe disease. "I do believe children at high risk do need to be vaccinated," remarked panelist James Hildreth, "but vaccinating all of the children to achieve that does seem a bit much for me."

'One-size-fits-all' approach?

Michael Kurilla, who was the only abstention, argued during the meeting that not all children in the five-to-11 age bracket will need two doses of a COVID-19 vaccine. He also suggested Pfizer and BioNTech could consider a different regimen than two shots three weeks apart, saying that "a one-size-fits-all" approach is not appropriate. He noted children who have had COVID-19 might already be protected, and the strain used to create the vaccine is now nearly two years old.

The FDA is likely to reach a decision before the Centers for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practices (ACIP) meets on November 2 and 3. If that review also turns out to be positive, it would clear the way for younger children to start receiving Comirnaty as soon as early November.

Eric Rubin, another member of the FDA advisory group, suggested that worries about the potential for rare side effects, especially myocarditis, are worth considering at the ACIP meeting. However, despite those concerns, Rubin said "we're never going to learn about how safe the vaccine is unless we start giving it…That's just the way it goes, and that's how we found out about rare complications of other vaccines."

Comirnaty, first granted an emergency-use authorisation in December 2020 for people ages 16 and older, has since received full FDA approval in this group. It has been authorised for emergency use in children as young as 12 since May.

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