Pfizer's request to roll out COVID-19 vaccines for Americans cleared a key regulatory hurdle Tuesday, after a panel of the Food and Drug Administration's outside vaccine advisers voted by a majority to back Pfizer's request.
The vote is a crucial step towards vaccinations for younger children, but not the final word. If the FDA decides to formally authorize the vaccine, the Centers for Disease Control and Prevention must also weigh in with its own recommendations before shots can be rolled out.
"I do think we need it as a tool in our armamentarium for high risk children, for equity issues, for parents who really would like to protect their children, and because of the long term, very profound implications of schools being disrupted," Dr. Mark Sawyer, one of the panel's members, said ahead of the vote.
Seventeen members of the committee voted in favor of authorizing the shots, and one abstained.
The decision follows a day-long meeting of the FDA's Vaccines and Related Biological Products Advisory Committee, which has grappled for months with how to balance the benefits of the vaccine for younger children against the potential risks of rare side effects.
Many of the panel's members voiced concern over some unanswered questions over rare side effects from the vaccine, but sided with allowing parents to weigh the benefits and risks for their children.
"We should certainly not underestimate the knowledge and decision-making power of the public," VRBPAC member Dr. Michael Nelson said, calling it "an access and really a personal choice and equity question, and not a mandate for all in this age."
While children are far less likely than adults to get severely ill or die from COVID-19, data presented to the committee on Tuesday suggests that they can be just as likely to catch and spread the disease.
"Far from being spared from this harm of COVID-19, in the 5-to-11-year-old age range there have been over 1.9 million infections, over 8,300 hospitalizations, about a third of which have required intensive care unit stays, and over 2,500 cases of multisystem inflammatory disorder from COVID-19," Dr. Peter Marks, the FDA's top vaccines official, told the panel as it began its meeting.
The FDA's advisers were also presented with figures tallying the growing toll of the disease in younger children, underscoring a public health need to avert more severe cases and other disruptions from.
"There have also been close to 100 [COVID-19] deaths, making it one of the top 10 causes of death in this age range during this time," added Marks.
Data from Pfizer's clinical trials suggest that smaller doses of its vaccine in children were highly effective at triggering antibodies to the virus, and could be more than 90% effective at blocking symptomatic disease.
The company's scientists acknowledged that the trial did not assess whether the pediatric vaccine could block transmission from asymptomatic cases of COVID-19, which have been a major drive of its spread. However, citing data from older age groups and its positive antibody results, Pfizer argued that it was "reasonable to expect that there will be some reduction in transmission."
"Vaccinating children has other large societal benefits: for example, children likely play an important role in transmission and vaccinating children can help reach herd immunity," Dr. William Gruber, Pfizer's senior vice president of vaccine clinical research and development, told the panel.
Weighing the risks and benefits
In weighing the risks of Pfizer's vaccine, much of the panel's discussion focused on concerns over rare cases of heart inflammation known as myocarditis and pericarditis, seen mostly in younger male recipients of the mRNA-based vaccines made by Pfizer and Moderna.
Other side effects and reactions seen from Pfizer's pediatric doses in children 5 to 11 years old were similar and sometimes less common than those recorded in adolescents and young adults, the company said. Rare events like myocarditis or anaphylaxis — severe allergic reactions to the shots that have been seen in a small number of adults — were probably too uncommon to be spotted in the clinical trials.
Though the reported cases of myocarditis and pericarditis after the vaccine in adolescents and adults have often been mild and resolved within a day, most required hospitalization. Early data from ongoing investigations by the CDC suggest that some continue to experience symptoms at least three months after they were first diagnosed.
Out of more than 400 million doses of the COVID-19 vaccines administered in the U.S., CDC officials said earlier this month that they had confirmed 877 reports of myocarditis or pericarditis potentially linked to the shots in Americans younger than 30 years old. After Pfizer's second dose in adolescents, the CDC said reporting rates of myocarditis totaled around 21.5 cases per million doses administered.
of Pfizer's request, the FDA estimated that if COVID-19 cases were to fall to the low levels last seen in June, it could be possible there might be fewer severe COVID-19 cases prevented than myocarditis or pericarditis cases potentially caused by the shots.
"The model results indicate that the benefits of the vaccine are highly dependent on the incidence of COVID-19," the FDA said.
Asked by the committee, Pfizer cited the FDA's own caveats around the limitations of its estimate, and warned it was likely cases may again surge in the coming months.
"Given that the winter season is coming, the Delta virus is still out there, you still have a large number of susceptible children, there's every reason to believe that the rate will not be at the nadir," said Gruber.
Only the FDA's "worst case" scenario estimated that the risk of myocarditis might outweigh its benefits in preventing severe COVID-19 cases. Beyond the shot's other benefits, other scenarios modeled by the FDA — including at current levels of the disease's spread in the U.S. — concluded that the severe COVID-19 cases prevented might "clearly outweigh" the risk of myocarditis.
The benefits estimated by the FDA could be a significant overestimate, officials acknowledged, after the CDC presented data suggesting more than 40% of U.S. children could have some immunity from a prior COVID-19 infection.
The risks could also be an overestimate, health officials cautioned, and amounted to a very "conservative" estimate. Data suggests adolescents could have lower rates of myocarditis after the vaccine than older children. That risk could be further reduced in younger children, given Pfizer's decision to reduce the size of its pediatric dose, the company said.
When could shots be available for kids?
After the FDA's formal authorization, the Biden administration says up to 15 million child-sized doses of Pfizer's vaccine could be shipped out to providers. Administration officials hope first doses could begin as early as the first week of November, pending final sign-off from the FDA and the CDC.
Under federal supply agreements, vaccinators will still need to wait for the CDC to formally recommend use of the shots before they can be put into arms. The CDC's own panel of vaccine advisers are scheduled to meet on November 2 and 3 to debate pediatric vaccinations.
Pfizer's smaller dose for younger children will arrive with packaging to distinguish the new formulation from its full-strength vaccine for adults, the company's executives told the VRBPAC's members. New changes to some of the vaccine's ingredients will also help more than double its shelf life in pharmacy refrigerators, while making it easier for vaccinators to draw up the smaller doses from vials.
The reduced dose could someday be expanded to adolescents as well, the company said. The FDA previously authorized adolescents to receive the full-strength 30 microgram doses of the vaccine given to adults.
"There is the potential, although we don't have the data to show it, for a 10 microgram dose to provide antibody response and we have some possibility of looking at that in the future, but we don't have that data today," said Pfizer's Dr. William Gruber.
Scientists at Pfizer decided to reduce its dose to just 10 micrograms for younger children, over concerns of reactions to the shot seen in the company's early trials.
"We are thinking about that as a potential option, particularly you know, as we move out of the pandemic period. The key goal right now is obviously providing protection with a safe and effective vaccine to get ahead of the pandemic," Gruber said.
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