VRBPAC recommends Pfizer, Moderna COVID vaccines for youngest children

Regulatory NewsRegulatory News | 15 June 2022 |  By 

On Wednesday, the US Food and Drug Administration’s (FDA) Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted in favor of amending FDA’s emergency use authorization (EUA) for Moderna’s two-dose vaccine to include children 6 months through 5 years of age. The committee voted separately in favor of recommending to amend Pfizer’s EUA for its vaccine and authorize use of a three-dose vaccine for children 6 months through 4 years of age.
In a 21-0 vote, VRBPAC members unanimously recommended that FDA authorize an EUA extension to Moderna’s vaccine, and voted unanimously to recommend FDA authorize an extension to Pfizer’s vaccine EUA. The official EUA extension by FDA is expected within the coming days. While FDA isn’t required to follow the recommendations of its advisory committees, it usually does.
The positive vote followed a VRBPAC meeting on Tuesday where the committee unanimously voted 22-0 to recommend Moderna’s COVID-19 vaccine as a two-dose series for EUA in children 6 years and older. (RELATED: VRBPAC unanimously backs Moderna vaccine for children 6 and up, Regulatory Focus 14 June 2022)
On the second day of the 2-day VRBPAC meeting, the questions under consideration by the committee were whether the benefits outweighed the risks to extend EUAs to the youngest age groups evaluated in Moderna and Pfizer’s clinical trials of their COVID-19 vaccines. Moderna sought an EUA for a two-dose vaccine at a dose level of 25 μg—a quarter of the 100 μg dose approved for use in adults—for children 6 months to under 6 years old, which will be taken 1 month apart.
Pfizer went a slightly different route than it has with other age groups, asking that the committee vote in favor to recommend authorization of a three-dose primary series vaccine at a dose level of 3 μg—a tenth of the 30 μg offered for adults—in children 6 months to under 5 years old. The first two doses are to be taken 3 weeks apart, with the third dose taken 8 weeks after the second.
An advisory committee meeting was originally scheduled for February 2022, where Pfizer would have discussed amending its EUA for a two-dose vaccine in children 6 months through 4 years old. However, that same month, the meeting requested was postponed to give Pfizer more time to analyze information about how adding a third dose to the two-dose series impacted patients in the clinical trial.
At the top of the meeting, Peter Marks, director of Center for Biologics Evaluation and Research (CBER), let the committee members know what was at stake with the vote, noting the high rate of hospitalizations in children during the omicron variant surge in the United States this past winter. “Just to remind people why we’re here, it’s because even though we have a very high seroprevalence rate of SARS-CoV-2 in the pediatric population, there still was during the omicron wave a relatively high rate of hospitalization during this period,” he said. “That rate of hospitalization is actually quite troubling, and if we compare this to what we see in a terrible influenza season, it is worse.”
The number of pediatric deaths up to late May 2022 is also much higher than what is normally seen with other diseases in children, Marks explained. He highlighted a statistic from the Centers for Disease Control and Prevention’s (CDC) presentation from the previous day, which showed 442 children under 4 years old had died from COVID-19 as of 28 May. “That also compares quite terrible to what we’ve seen in influenza in the past,” he said. During the H1N1 influenza pandemic in 2009-10, for example, there were 78 deaths in children under 4.
“I think we have to be careful that we don’t become numb to the number of pediatric deaths because of the overwhelming number of older deaths here,” Marks said. “Every life is important, and vaccine-preventable deaths are ones that we would like to do something about.”
Moderna’s two-dose vaccine
Study 204, Moderna’s trial for young children, evaluated infants and toddlers 6-23 months old and children 2-5 years old, and the company compared the results to young adults who received a full-strength dose of the vaccine. The results of the study showed comparable neutralizing antibody geometric mean titers in children 6 months to under 6 years old compared with adolescents and adults. Moderna also estimated efficacy against symptomatic COVID-19 as a secondary objective and reported the vaccine efficacy against the omicron variant was 50.6% for children 23 months and younger and 36.8% for children 2 years to under 6 years old compared with a placebo group based on the Centers for Disease Control (CDC) case definition of COVID-19.
In a discussion session surrounding the Moderna vaccine’s vote, some committee members expressed concern about whether the vaccine was necessary for all children given a low rate of COVID-19 related hospitalization relative to other age groups, while other members disagreed with that characterization of hospitalizations in young children.
Cody Meissner, MD, director of pediatric infectious diseases at Tufts University School of Medicine in Boston, said he was in favor of the vote, but noted the messaging around the vaccine for children in this age group should include “the relative risk and relative benefit.”
Jay Portnoy, MD, professor of pediatrics at Children’s Mercy Hospital in Kansas City, MO, said he was moved by the public comment portion of the meeting where parents shared their experiences of trying to keep their children safe from COVID-19. He recalled what it was like this past winter seeing a full emergency room at his pediatric hospital.
“I know that the death rate from COVID in young children may not be extremely high, but it’s absolutely terrifying to parents to have their child be sick, have to go to the hospital, or even go to the emergency room or their primary care doctor because they’re sick and having trouble breathing,” Portnoy said. “It’s not just doubts. We have to understand how distressing this is for parents whose children are affected by this disease.”
Arthur Reingold, MD, professor of epidemiology division head in the Epidemiology School of Public Health at the University of California, Berkeley, noted that it’s reasonable to make the vaccine available because the benefits outweigh the risks.
“I would point out that we as a country continue to give a large number of vaccines to children where the risk of the child dying or being hospitalized of those diseases is pretty close to zero,” he said. “I do think we do need to focus on the serious outcomes, even if they’re relatively infrequent, and even if a vaccine is less than 100% effective.”
Pfizer’s three-dose vaccine
Pfizer presented their results for their 3-dose, 3 μg vaccine for children 6 months to less than 2 years, and for children 2 years of age to less than 5 years old. The company spent the beginning part of their presentation outlining their rationale for using a 3 μg dose vaccine for this age group, arguing that parents would be more likely to adopt an effective pediatric vaccine that resulted in fewer side effects like fevers.
One major point of discussion was the efficacy of Pfizer’s vaccine after two of the three doses had been administered in the series. Following FDA’s presentation of Pfizer’s data, committee member Paul Offit, MD, professor of pediatrics at The Children’s Hospital of Philadelphia, posed a question to FDA about why the data showed Moderna’s vaccine was more protective at two doses for participants under 5 years old compared with Pfizer’s vaccine. In other age groups up until this point, the efficacy was similar between the two mRNA vaccines, he pointed out.
“This is the first time you’re really seeing a difference in the less than 5-year-olds, where the two dose of Moderna offered some protection, whereas that wasn’t true at all with Pfizer vaccine,” Offit said in an FDA question-and-answer session.
“It does worry me, actually, that there was no protection after dose 2. That was surprising. I think it was probably surprising to the company, and I fear that they may have underdosed,” Offit said later prior to the vote. However, he noted that he supported amending Pfizer’s EUA to include the vaccine.
In closing the meeting out, Marks took a moment to recognize the authorization of COVID-19 vaccines for young children is “a bit of a milestone,” and said the FDA would continue to monitor the vaccines as they are deployed.


© 2023 Regulatory Affairs Professionals Society.

Discover more of what matters to you