Moderna to ask FDA to authorize Covid-19 vaccine in children 6 months to 6 years

Moderna announced Wednesday that it will ask the Food and Drug Administration to authorize its Covid-19 vaccine for emergency use in children aged 6 months to 6 years, a group for which there are currently no authorized Covid vaccines.

The company’s announcement came as it released interim data from two clinical trials of its vaccine in children under 6 years of age. Moderna said the studies — in children aged 6 months to 23 months and 2 years to 6 years — showed the vaccine generated similar immune responses as those seen in adults aged 18 to 25 who received two doses of Moderna’s adult Covid vaccine.

“Given the need for a vaccine against COVID-19 in infants and young children we are working with the U.S. FDA and regulators globally to submit these data as soon as possible,” Moderna CEO Stéphane Bancel said in a statement.

However, the two-dose vaccine was less effective at preventing symptomatic infection — meaning that subjects had symptoms and then a positive Covid test — than vaccines have been in previous trials for older age groups. In children 6 months to 23 months, cases of Covid were decreased 43.7%; they were decreased by 37.5% in the 2 years to under 6 years age group. Moderna said that the efficacy was on par with what would be expected of a two-dose vaccine in adults against the Omicron variant, which predominated during the trial. The Omicron variant contains mutations that allow it to evade immunity built up by both vaccination and prior infection.

There were no severe cases, hospitalizations, or deaths in the studies, so the company could not estimate how protective the vaccine was in young children against those outcomes.

“A [vaccine efficacy] of 40% with adequate safety data could be very meaningful, especially to higher risk individuals,” said Luciana Borio, a former FDA acting chief scientist who is now a partner at Arch Venture Partners. One possibility, she said, would be to authorize the vaccine and recommend it for children with underlying medical conditions. But, she said, the FDA should hold an advisory committee to review the data first.

The FDA’s guidance to vaccine manufacturers at the beginning of the quest for Covid vaccines called for vaccines to cut the risk of infection by at least 50%. But all the currently available vaccines were approved or authorized before the emergence of variants like Omicron. Most probably would not have passed muster had Omicron emerged while their initial clinical trials were underway.

“If we were to re-run clinical trials for older age groups in the age of Omicron I feel like we would get similar results, and that has to shape our discussions a little bit,” said Natalie Dean, an assistant professor of biostatistics at the Emory Rollins School of Public Health. “I think about what frame of reference the FDA and other regulators are going to have about what the level of efficacy needs to be.”

Dean suggested it may turn out that a third dose is needed in children. Moderna said it will study booster shots in children under age 6, as it is doing in older children.

Phil Krause, a former deputy director of the FDA’s office of vaccines, saw some ambiguity in the results. The trials showed that the vaccine induced in young children immune responses similar to those seen in older teens and young adults. But there is reason to question whether that is predictive of protection, Krause said.

A recent study from New York State showed that the Pfizer vaccine’s protection in children aged 5 to 11 waned markedly quicker than would have been expected — even though use of the vaccine in that age group was authorized based on a study showing it generated similar levels of antibodies as seen in older teens and young adults who had been vaccinated.

That raises questions about how well what is seen in adults vaccinated with adult-sized doses can predict protection in children vaccinated with lower doses, he suggested.

“It may be that it’s impossible to get these vaccines to work as well in children as they do in adults,” said Krause, who is now a consultant. (He does not consult on Covid vaccines with pharmaceutical companies.) “There may still be some benefit in using these vaccines, but it will then be tricky and important to make sure that people understand the limitations of what can be said about the vaccines and the limitations in what to expect the vaccines to do.”

Bancel also said that after consulting with the FDA, Moderna has initiated an application for authorization of the vaccine for children aged 6 to 11, and is updating its submission for children 12 to 17 years old, which has been pending since last year. A number of other countries, including Canada, have authorized Moderna’s vaccine for teens and children as young as 6.

In the United States, however, Moderna has trailed its major competitor, Pfizer and its partner BioNTech, into the market for teens and children. While the Pfizer vaccine is authorized for use in children aged 5 and older, the use of the Moderna vaccine is still limited to adults aged 18 and older. Both vaccines use messenger RNA to coax the immune system to generate protection against SARS-CoV-2, the virus that causes Covid.

But Pfizer hit a snag in the clinical trials testing its vaccine in children under the age of 5, when two doses of the vaccine — given at one-tenth of the amount used in adults — did not generate immune responses similar to those seen in older teens and young adults. The company announced in December that it was going to test a third dose in children under 5. That work is still underway.

In children under the age of 6, Moderna tested two doses of 25 micrograms apiece, given 28 days apart. Adults receive four times that much vaccine in two doses given over the same time frame. In the trials, in which some children were randomized to receive a placebo and others the vaccine, there were 2,500 children aged 6 months to 23 months and 4,200 children aged 2 to 6 years.

Moderna said the side-effect profile was favorable, with the rate of fevers over 100.4 Fahrenheit occurring at a rate consistent with what is seen with other pediatric vaccines. Fevers of this magnitude were seen in 17% of babies under 2 years and 14.6% of children aged 2 to 6; by contrast, nearly 24% of children aged 6 to 12 recorded fevers over 100.4 Fahrenheit, though the older children received doses that were twice as large as those given to the younger kids. A small number of children — 0.2% in each age group — experienced fevers over 104 Fahrenheit after vaccination.

The company said there were no deaths and no cases of myocarditis or pericarditis — conditions involving inflammation of the heart or the tissue around the heart that have been seen both after vaccination with an mRNA vaccine and after Covid infection. There were also no reported cases of multisystem inflammatory syndrome, or MIS-C.