In a sudden reversal, the Food and Drug Administration on Friday said it would delay review of the Pfizer vaccine for babies and toddlers until at least April, another setback for the only age group that does not have access to a vaccine.
The agency said it needed more time to review data from a third dose of the vaccine that Pfizer began testing in young children after getting mixed results from its trial of the original two-dose regimen.
“The data we saw made us realize we needed to see data from a third dose in order to make a determination,” said Dr. Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, in a media briefing following the announcement.
The development adds to the controversy over the FDA’s decision to review a vaccine with questionable effectiveness. In December, Pfizer reported on results of its trial of the two-dose vaccination, saying it found immune responses met expectations in children 6 to 23 months but not in children ages 2 to 4.
The company then began testing a third shot of the vaccine in both groups, hoping for better results.
But in early February, the FDA surprised doctors and parents by asking Pfizer to submit data from its two-dose regimen before the company had results from the test of the third shot.
The unorthodox decision made doctors wonder if the FDA would authorize the vaccine without solid evidence that it worked.
“That is not the way the system ordinarily runs,” said Dr. H. Cody Meissner, chief of the Division of Pediatric Infectious Disease at Tufts Children’s Hospital. “But people feel that the pandemic is upon us and they want to do as much as they can to get it under control.”
The FDA’s vaccine advisory committee, an independent panel of doctors and scientists on which Meissner serves, was due to convene on Tuesday to discuss the data and vote on whether the FDA should authorize the two-dose regimen for children under 5, with the expectation that a third dose would be needed later.
On Friday, the FDA was expected to publish complete data from Pfizer’s two-dose clinical trial, but did not. Meissner speculates that Pfizer and the FDA delayed the meeting because of reservations among doctors and scientists about the two-dose vaccine.
“It might have been rough sledding at the meeting. I think the company anticipated that,” Meissner said. It was “an appropriate decision” to delay the meeting, he added.
Dr. Kristin Moffitt, a pediatrician at Boston Children’s Hospital who specializes in infectious diseases, had supported vaccinating young children even if the doses weren’t fully protective, since the Pfizer trials identified no safety concerns.
She said on Friday that the delay was “unfortunate” but might reflect fears by FDA officials that their agency could lose credibility if it authorized two shots that ended up not being effective in some young children.
Dr. Paul Offit, a member of the FDA advisory committee and director of the Vaccine Education Center at Children’s Hospital of Philadelphia, was glad the agency canceled next week’s meeting.
“We were being asked to evaluate a three-dose vaccine after having data on only two doses, which would have meant that we would have to assume that the efficacy was better after the third dose, which is not necessarily true but likely,” he said.
“But more importantly, we’d have to assume that the safety profile was the same after the third dose,” he said. “I’m glad we’re going to wait until we have all the data. That’s the most fair thing to do for the parents and these children.”
Pfizer’s vaccine has full FDA approval for ages 16 and up, and is authorized for use in ages 5 through 15. Previous clinical trials found that two shots of the vaccine were more than 90 percent effective in older children and adults. Moderna is still testing its COVID-19 vaccine in young children, and expects to report data on children ages 2 to 5 in March.
Without seeing Pfizer’s data on the two-dose vaccine in young children, scientists could only speculate about why results from the trial were underwhelming.
The discrepancy between the age groups could be due to the particularly low dose, at 3 micrograms, that Pfizer selected for children under 5, only one-10th of the 30-microgram dose that people 16 and older receive. Dr. Stephen Spector, chief of the Division of Pediatric Infectious Diseases at UC San Diego School of Medicine, said the 3-microgram dose may have been sufficient for infants 6 to 23 months, but not enough for children 2 to 4.
Moderna is testing a considerably larger 25-microgram dose in children 2 to 5, which is one-fourth of the 100-microgram dose that adults get.
Researchers also note that the Delta and Omicron variants of the virus — not widely circulating during earlier trials of the vaccine — could be responsible for the lackluster findings. Both viruses, and Omicron in particular, are able to evade some of the antibodies generated by the vaccines.
Others point out that it’s still not known if young children need to generate the same high levels of antibodies as teens and adults to be protected from COVID. Because hospitalizations and deaths are rare in children, Pfizer measured effectiveness in its pediatric clinical trials by comparing antibody levels in younger kids with those of older teenagers and young adults.
“What’s interesting, and unknown, is whether kids need the same level of immunity as generated in adults to be protected from COVID,” says Dr. Clarence Buddy Creech II, director of the Vanderbilt Vaccine Research Program and president of the Pediatric Infectious Diseases Society. ”For those of us who are seeing these kids in the hospital infected with Omicron, and for parents who are hoping for a vaccine soon, I think we’d all gladly accept a vaccine that protects against COVID, whether or not it meets a pre-specified amount of antibodies in the bloodstream.”
At the FDA media briefing, Marks suggested that waiting longer and collecting more data would give the FDA a chance to make its decision based on actual infection rates among vaccinated and unvaccinated children rather than on antibody levels alone.
Not everyone agreed with the FDA’s decision to delay its meeting. Dr. Alpa Patel Shah, a Milwaukee pediatrician who is among roughly 500 doctors who signed a recent letter to acting FDA Commissioner Janet Woodcock urging the agency to authorize two shots for the youngest kids, said she is “disappointed and frustrated about the lack of transparency from the FDA.”
“We were expecting hard data today,” she said. “Instead, we took several steps back and the reason is still unclear. As a consequence, once again, children are being left behind.”
Other doctors note that while Omicron infections remain a major problem, cases are falling rapidly. That may factor into the decision to delay the vaccine for young children, and get a better grasp on just how well the vaccine works.
“It is a tough call, but if we give this a few more weeks or months, we can have a more solid decision,” says Dr. Ofer Levy, director of the Precision Vaccines Program at Boston Children’s Hospital and a professor of pediatrics at Harvard Medical School.
“I don’t envy the FDA decision-makers, they are in a tough spot. They are getting simultaneously criticized for being too fast and too slow.”