A group of advisers to the Food and Drug Administration will meet Tuesday to discuss one of the most important questions since coronavirus vaccines first became available last year: whether to make them available to young children.
Their recommendation could pave the way for the roughly 28 million Americans between 5 and 11 years old to receive Pfizer and BioNTech's vaccine, a potential turning point in the pandemic. A positive outcome is anticipated by the Biden administration, which, as with booster shots earlier this summer, detailed its rollout plans before drug regulators made their decision.
But, also as with boosters, the questions facing Tuesday's panel may not have easy answers. Children are not just small adults; the benefits and risks of vaccination are different, especially as kids seem less vulnerable to COVID-19's worst outcomes.
A transparent review is critical. A recent Kaiser Family Foundation poll found only about a third of parents of children between 5 and 11 plan to vaccinate their kids immediately after a shot is available, reflecting the uncertainty and communication challenges ahead for public health officials eager to see kids protected.
The FDA will broadcast its meeting, which runs from 8:00 am to 5:00 pm Tuesday, and BioPharma Dive will cover live. Here's what we know so far:
How important are vaccinations for kids?
Since the pandemic began, it's become clear the people most susceptible to COVID-19's worst effects are either older or have underlying health conditions. But coronavirus infections can harm or even kill younger and seemingly healthy individuals, too, and easily spread from infected, but unaffected, individual to those more vulnerable.
Such is the case with children. As of Oct. 14, about 1.8 million children between 5 and 11 are confirmed to have tested positive for COVID-19 during the pandemic, according to the Centers for Disease Control and Prevention. The share of cases they represent has increased as more adults were vaccinated and the infectious delta variant spread. Yet about half of childhood cases are asymptomatic, National Institute of Allergy and Infectious Disease director Anthony Fauci said earlier this week, and hospitalizations and deaths from COVID-19 are rare.
Still, small numbers can add up. The latest CDC data shows 8,622 COVID-related hospitalizations in 5- to 11-year-olds and 143 deaths, amounting to a "pediatric burden [that] ... likely exceeds that of seasonal influenza," Pfizer scientists wrote in briefing documents published Friday.
It's also unclear what percentage of kids experience symptoms for several months or more, or what the long-term effects of an infection are. Recent research has shown that, unlike the original version of the coronavirus, delta is able to infect children and spread to others as easily as with adults, Fauci said. Vaccinating a majority of children "would play a major role in diminishing the spread of infection in the community," he said. That, in turn, could protect older family members and teachers, help keep schools open and lessen the burden on parents.
What's known about vaccine efficacy in kids?
Pfizer is leaning on testing it previously completed in teenagers and young adults to help prove its vaccine is effective in younger children.
Guidelines set by the FDA allow vaccine developers to demonstrate efficacy by showing immune responses to vaccination in kids are equivalent to those reported for older individuals.
Results from Pfizer's study of 5- to 11-year-olds met this bar. Two shots of a 10 microgram dose spurred antibody levels against the coronavirus that, on average, were almost identical to those earlier observed in 16- to 25-year olds who received a 30 microgram dose. While scientists have not yet agreed on an antibody threshold that correlates with immunity, higher antibody levels are generally linked with protection.
New data from the company, published in FDA briefing documents Friday, help support that association. Measured from seven days after the second dose, researchers running Pfizer's study reported three cases of COVID-19 among children who had received the vaccine, compared to 16 among those given placebo. That translated to a 90.7% efficacy estimate against symptomatic COVID-19, although the small numbers involved mean the true figure may be between 67% and 98%.
There were no cases of severe COVID-19 reported, nor were there any cases among children who previously had been infected.
Pfizer also noted that the first case in the study was identified in July, meaning all of the infections reported occurred at a time when the more contagious delta variant was prevalent in the U.S.
Still, there are limitations to the data. The study's size — immune response and efficacy data are drawn from about 2,250 kids — was much smaller than the larger Phase 3 used to win approval in adults.
Without a defined antibody threshold for protection, it's also not certain whether kids will be as protected from COVID-19 as older teenagers and adults based on similar immune responses.
Furthermore, Pfizer's follow-up on the reported COVID-19 cases only goes out roughly four months after participants' first doses. It's unclear, therefore, whether protection is similarly durable in kids as in adults.
How safe is Pfizer's vaccine for kids?
The bar for safety is exceedingly high for a vaccine meant to be given to millions of children, especially as Pfizer wants its shot authorized for use in all 5- to 11-year-olds. So experts will scrutinize the known side effects associated with Pfizer's shot, as well as the potential limitations of the data the company has submitted.
Chief among the FDA advisers' concerns is likely to be the risk of a type of heart inflammation known as myocarditis, an uncommon side effect of Pfizer's shot that has primarily been observed in adolescents and younger men. Cases associated with vaccination typically occur within a week of the second shot, according to the CDC. Most are mild and lead to full recovery. Myocarditis is also associated with several diseases caused by viruses, among them COVID-19.
Yet the risk of myocarditis has caught the eye of the FDA and its panel. Real-world data from Israel showed rates of about 8 to 16 per 100,000 doses in young men aged 12 to 29. The growing body of evidence reportedly led the FDA to require Pfizer and Moderna boost the size of their trials to better detect cases. Multiple FDA advisers, meanwhile, were hesitant to authorize boosters for younger adults without more information about the risk. The FDA has specifically devoted a session to the issue at Tuesday's meeting.
Pfizer didn't observe any cases of myocarditis in the trial supporting its application for use in kids. The Israeli data also shows that myocarditis rates are lower in adolescents than in 16- to 19-year-olds. The dose for children is a third of the size, so it is "reasonable to predict" myocarditis will be less frequent in kids, Pfizer scientists wrote.
But there are important limitations to those findings. Pfizer's trial initially enrolled about 2,250 volunteers and 1,500 received the vaccine, meaning it was still too small to properly assess the risk of myocarditis. Participants have only been tracked for about two months post-vaccination, a shorter follow-up period than usual for vaccines. As a result, the company, plans to run five post-authorization studies to evaluate any long-term effects, briefing documents show.
Pfizer didn't report any other serious adverse reactions that investigators judged to be caused by vaccination among kids in the study. Pain, swelling and redness were the most common side effects and mostly mild in nature. Swelling of the lymph nodes was also more frequent in vaccinated participants than placebo recipients.
What does the FDA think of the results?
In briefing documents posted Friday evening, FDA scientists were clearly supportive of Pfizer's data, a contrast to the more muted review agency staff gave the requests Pfizer and others made for booster shot authorizations.
The bulk of the document centered on myocarditis and whether that risk was greater than the benefit of vaccination. FDA used statistical models to compare the predicted number of symptomatic COVID-19 cases, hospitalizations and deaths prevented in a mass vaccination campaign to the number of children who might end up hospitalized due to vaccine-associated myocarditis.
Those models assumed a variety of scenarios, including low and high case rates and different levels of vaccine effectiveness. They also assumed kids might have the same expected rate of myocarditis as 12- to 15-year-olds, even though adolescents receive a higher dose.
FDA reviewers found the magnitude of the benefits of vaccination were "highly dependent" on how widely the virus was spreading, but "clearly outweigh[ed]" the risks of myocarditis in almost every scenario, the document said. Even when case rates are low and the chances of myocarditis-related hospitalization exceed the chances of being hospitalized with COVID-19, the prospect of preventing milder cases that involve serious, long-lasting complications favored vaccination.
The advantage would be more stark if kids between 5 and 11 are indeed less likely to experience heart inflammation, FDA reviewers said, as Pfizer argues.