Near-unanimous adcomm nod on Pfizer COVID vaccine for younger kids

Regulatory NewsRegulatory News | 26 October 2021 |  By 

Younger school-aged children in the US came a step closer on Tuesday to having a COVID-19 vaccine available, with a positive vote from the US Food and Drug Administration's (FDA's) vaccines advisory committee for a reduced dose of Pfizer’s mRNA vaccine.
The vote was near-unanimous, with just one abstention and no “nays” among the 18 voting members of FDA’s Vaccines and Related Biological Products advisory committee (VRBPAC). Overall, the committee judged that the benefits of two 10 mcg doses of Pfizer’s mRNA vaccine Comirnaty outweighed risks of administration for children aged 5 through 11 years of age.

The committee vote came after a day-long meeting to review Pfizer’s request to extend the emergency use authorization for Comirnaty to include younger school-aged children.
Though the vote tally would indicate robust endorsement from the committee, the day’s presentations and discussions unfolded a more nuanced picture, with lingering concerns about a signal for myocarditis and pericarditis in older adolescents and young adults, and uncertainty about how to model risk amid the pandemic’s still-uncertain trajectory.
At no point were the robust efficacy numbers, which topped 90% after two doses administered 3 weeks apart, in question. Pfizer also presented clinical trial safety data that were overall reassuring, with minimal local and systemic reactions to the first vaccine dose and, and second-dose safety data that largely mirrored that seen in the12-17-year age group.
Seroprevalence high in children
Many committee members seemed shaken by data presented by the US Centers for Disease Control and Prevention (CDC) showing that seroprevalence for SARS-CoV-2 antibodies among children aged 5-11 years reached 42% by June of this year.
The FDA benefit-risk analysis did not take background seropositivity into account when it crafted three scenarios for estimating childhood vaccination benefit and risk that depended on background incidence rates of COVID-19, since it’s not known how well prior COVID-19 infection protects against future disease. Paul Offit, a pediatric infectious disease and vaccine specialist at The Children’s Hospital of Pennsylvania who also sits on the CDC’s Advisory Committee on Immunization Practices (ACIP), teased out these details of FDA’s analysis in his questioning after FDA’s presentation.
“You are probably protected against serious infection” after prior COVID-19 infection, said Offit; the depth and duration of that protection are not yet known, and may also be affected by yet-unquantified variables.
The myocarditis question
The committee was asked to weigh efficacy data and considerations about prior infection and point prevalence of COVID-19 against reporting rates of myocarditis among males who have received mRNA COVID-19 vaccines that “exceed background incidence,” according to the CDC presentation. The highest rate seen in data from the Vaccine Adverse Event Reporting System (VAERS) has been among males aged 16 to 17 years, for whom VAERS data show a rate of 0.007%.
“This is a much tougher call than we thought coming into it,” said VRBPAC member Eric Rubin, an immunologist and editor-in-chief of The New England Journal of Medicine. “We’re worried about a side effect that we can’t measure yet. For me, it’s going to revolve around two questions: first off, whether there is going to be a use for this vaccine in this age group, and then how the decision gets made to use it within this age group. It’s a very personal choice. If I had a child who was a transplant recipient, I would certainly want to use a vaccine like this. And then there are kids who probably shouldn’t be vaccinated,” he concluded.
“Surveillance systems are going to be critical,” said committee member Ofer Levy, who directs the precision vaccines program in the infectious diseases division at Boston Children’s Hospital. “We do need ongoing efforts to characterize the disease in children” as well, he noted.
Levy, also a Harvard Medical School professor, observed that “a priori, it seems that the 5-11 age group may be less susceptible” to myocarditis after mRNA vaccination than the older adolescent and young adult population who have been more extensively studied.
“COVID-19 is now a vaccine-preventable disease in my perspective,” said VRBPAC member Amanda Cohn. Cohn, who is CDC’s staff medical officer for ACIP, noted that COVID-19 has been among the leading causes of death in the age group in question.
“We will monitor myocarditis very carefully — and I will say that there have been no deaths from myocarditis” resulting from mRNA vaccinations, Cohn said, adding that nearly all of the vaccine recipients who developed myocarditis have “completely recovered” from myocarditis during follow-up. CDC presented data showing that recovery of normal cardiac ejection fraction happens much more quickly in cases of vaccine-related myocarditis than in “classic” myocarditis or in that associated with multisystem inflammatory syndrome in children (MIS-C) related to COVID-19.
Jay Portnoy, the patient representative, is himself a professor of pediatrics at Children’s Mercy Hospital, Kansas City, MO. He thanked FDA and the committee for the “open and transparent discussion” on the question of benefits and risks of vaccinating children, adding that the process will ease his job of shared decision-making with families.
FDA is not obligated to follow the advice of its advisory committees, though it usually does. If the agency extends Comirnaty’s emergency use authorization to the children aged 5 to 11 years, ACIP will set clinical guardrails around any vaccine rollout. The next ACIP meeting is set for 2 and 3 November, with no agenda yet posted.

VRBPAC webcast and briefing materials


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