An advisory committee has recommended that the US Food and Drug Administration (FDA) give emergency use authorisation (EUA) to both Moderna and Pfizer/BioNTech’s mRNA COVID-19 vaccines for infants, toddlers and pre-school children.
The Vaccines and Related Biological Products Advisory Committee (VRBPAC) last week voted 21-0 in favour of expanded access to each vaccine, in another unanimous decision that the benefits of the vaccines outweigh the risks in these children, reports Medpage Today.
Moderna is seeking authorisation for two 25-mcg doses administered three weeks apart for infants aged six months up to five-year-olds, while Pfizer’s request is for three 3-mcg doses for children aged six months to four-years-old, which would be administered three weeks apart between the first and second shots, and eight weeks later for the third.
Several members of the advisory committee agreed on the importance of giving families the choice to vaccinate their under-fives – a group still waiting for access to the vaccine.
However, the committee was split on the risks from COVID-19 in this age group. While some said many children who become infected get mild illness, others noted the severe outcomes that some youngsters have experienced compared with other disease outbreaks.
Dr Peter Marks, director of the FDA’s Centre for Biologics Evaluation and Research, said there was a “troubling” rate of hospitalisations among children during the Omicron surge, worse than typically seen in a terrible influenza season. As of 28 May, there had been 442 COVID-related deaths in children under four, according to the US Centre for Disease Control (CDC).
“I think we have to be careful that we don’t become numb to the number of paediatric deaths because of the overwhelming number of older deaths here,” Marks said.
Some members voiced concerns about the efficacy of the Pfizer vaccine, specifically after the first two doses. Dr Paul Offit of the Children’s Hospital of Philadelphia said he was surprised that there was “no protection” after the second dose, noting the importance of communicating to families that their child might have to wait a few months before the vaccine was effective.
“I worry that parents aren’t necessarily going to know that after two doses, they may not be protected at all,” he said.
Data on Moderna’s two-dose COVID-19 vaccine, released in FDA briefing documents last week, came from mRNA-1273-P204, an ongoing phase II/III clinical trial that included 4,000 children aged two to five (3,000 of whom received the vaccine and 1,000 who received a placebo), as well as 2,350 children ages six to 23 months (1,761 who received the vaccine and 589 who received a placebo).
The median duration of follow-up was about two months for both age groups.
The Moderna vaccine met immuno-bridging success criteria in both groups. Neutralising antibody geometric mean titers and seroresponse rates were non-inferior to those seen in adults aged 18 to 25.
Preliminary vaccine efficacy was 36.8% (95% CI 12.5-54.0) for those ages two to five, and 50.6% (95% CI 21.4-68.6) for those aged six to 23 months. Efficacy was evaluated during a period when the Omicron variant was predominant.
Adverse events were mild to moderate in severity. Fevers were more common in the vaccine group than the placebo group, and occurred more frequently after the second dose. Rates of fever among the youngest age group were 21-26%, with a high fever (over 104°F) reported in less than 0.4% of children in this cohort.
A separate FDA briefing document included data on the efficacy of Pfizer/BioNTech's three-dose COVID vaccination series among children aged six months to four years. Study C4591007, an ongoing phase II/III trial, included 1,835 vaccine recipients and 915 placebo recipients ages two to four years, and 1,178 vaccine recipients and 598 placebo recipients ages six to 23 months.
The Pfizer vaccine also met immun-obridging success criteria for both age groups. Neutralising antibody geometric mean titers and seroresponse rates were non-inferior to those seen in young adults aged 16 to 25.
Vaccine efficacy among both groups combined was 80.4% (95% CI 14.1-96.7), and was 75.6% (95% CI -369.1 to 99.6) for those ages 6 to 23 months, and 82.4% (95% CI -7.6 to 98.3) for those ages 2 to 4 years.
Overall, three COVID-19 cases were reported in participants who received the vaccine versus seven in the placebo group.
Common adverse reactions among infants and toddlers included irritability, drowsiness, decreased appetite, and tenderness at the injection site. Among two to four-year-olds, common side effects were pain and redness at the injection site and fatigue.
There were no reported cases of myocarditis or pericarditis for either vaccine.
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