External advisors to the Food and Drug Administration voted unanimously on Wednesday to recommend that the agency release Moderna’s coronavirus vaccine for very young children, a move likely to pave the way for emergency vaccine approval later this week.
Panelists would vote later Wednesday afternoon on whether or not to recommend approval of Pfizer-BioNTech’s triple injection for children under age 5. Moderna’s dual vaccine is for children 6 months to 5 years old. (Watch the meeting live here.)
The FDA has said the companies’ clinical trial data shows that each vaccine met the criteria for safety and effectiveness in the age group.
More than two years after the pandemic, no vaccine has been approved in the United States for children under the age of 5, an unmet need that has baffled many parents. The FDA and the Centers for Disease Control and Prevention could act by the end of this week.
The panel of advisors voted 21-0 to recommend approval of Moderna’s pediatric vaccine. “I know the death rate from Covid and young children may not be extremely high,” Dr. Jay Portnoy, professor of pediatrics at Children’s Mercy Hospital in Kansas City, Mo. But he said, “It’s absolutely terrifying for parents.”
Regulators and company officials spent much of the day discussing side effects caused by vaccines, the vast majority of which were mild and tolerated in children in clinical trials: irritability and crying, drowsiness, fatigue and loss of appetite. Smaller numbers of trial participants had fevers, most of which did not exceed severe levels.
In younger age groups, fevers can be more debilitating and require more urgent medical attention, a dynamic that puts significant pressure on manufacturers to calibrate dosage correctly. Pfizer chose a dose only one-tenth the adult dose given in three shots; the first two are administered three weeks apart, and the third comes at least eight weeks after the second. Moderna used a quarter of the strength of the adult dose, given in two shots, four weeks apart.
Some difficult questions remain. Perhaps most importantly, neither vaccine has been tested against subvariants circulating in the United States. The clinical trials were largely conducted when the Omicron variant prevailed. Two subvariants, BA.4 and BA.5, could become dominant within a month.
The need to protect these children from Covid is great, Dr. Peter Marks, the FDA’s chief vaccine regulator, said at the meeting. He added that hundreds of children had died from Covid, a percentage he says is “quite related” to pediatric deaths during a major flu wave in 2009 and 2010.
Both vaccines under consideration on Wednesday appear to be significantly less effective against symptomatic infection than the adult vaccines when they were introduced. The FDA attributes that Omicron is much more adept at evading the vaccines’ defenses against infection than the original version of the virus.
Given the declining protection seen in adult recipients and the rapid evolution of the virus, regulators have said that children who were to receive the vaccines from Pfizer and Moderna would most likely need a booster. That would mean that Pfizer’s vaccine, developed with German company BioNTech, could end up as four doses, while Moderna’s could be three.
Both the Pfizer-BioNTech and Moderna vaccines produced levels of neutralizing or virus-blocking antibodies in children similar to those seen in teens and young adults ages 16 to 25. Pfizer’s vaccine has been approved for children ages 5 to 15 since last year, and regulators said it helped prevent hospitalizations and deaths.
After two doses, Pfizer’s vaccine was only 28 percent effective at preventing symptomatic infection in children 6 months through 4 years of age. Pfizer has suggested that the vaccine was 80 percent effective after a third dose, but the finding was based on just 10 cases from a subset of the 1,678 study participants. The study protocol specified that vaccine efficacy assessments should be based on at least twice as many cases; the small number of cases on which the efficacy finding was based was a topic of consternation among committee members and regulators on Wednesday.
dr. Doran Fink, a senior federal vaccine regulator, called Pfizer’s efficacy data tentative. “We consider it inaccurate and potentially unstable,” he said. “Exactly what vaccine efficacy is after dose three needs further data.”
Moderna found that the vaccine was 51 percent effective in preventing symptomatic infection in children 6 months to 2 years old, and 37 percent effective in children 2 through 5. Those results seem consistent with those reported in studies of adults during the Omicron era, the FDA said. Still, immunization continues to provide strong protection against serious illnesses leading to hospitalization and death.
A panelist on Wednesday asked if there was evidence of how children who had recovered from the virus responded to the vaccine — a common question among parents.
A Moderna official said the company’s study showed that young children who received Omicron and were vaccinated had a higher degree of protection, a conclusion supported by external research.
Although Moderna’s efficacy data seemed slightly stronger than Pfizer’s, scientists strongly cautioned against such comparisons.
“These are different populations. The studies were conducted at different times. The results are reported in different ways, with different endpoints,” said Dr. Jesse L. Goodman, a former chief scientist for the FDA. “Scientifically, we don’t have a direct comparison.”
