Pfizer and BioNTech have submitted data supporting the vaccination of children 5 to 12 years of age with Comirnaty (Covid-19 mRNA vaccine) to the European Medicines Agency (EMA) for a variation of the Conditional Marketing Authorization (CMA) in the European Union (EU). According to The New York Times, federal regulators evaluated the safety and efficacy of this vaccine, saying that the benefits of protecting people in that age group from Covid-19 with the Pfizer-BioNTech vaccine generally outweighed the risks of the most worrisome possible side effects.
The variation request includes data from a Phase II/III study, which is enrolling children six months to 12 years of age. The 2,268 participants who were 5 to 12 years of age received a 10-µg dose level in a two-dose regimen administered 21 days apart. In the trial, the SARS-CoV-2–neutralising antibody geometric mean titer (GMT) was 1,197.6 (95% confidence interval [CI, 1106.1, 1296.6]), demonstrating strong immune response in this cohort of children one month after the second dose. The antibody responses were comparable to those recorded in a previous Pfizer-BioNTech study in people 16 to 25 years of age immunised with 30-µg doses. The Covid-19 vaccine was well tolerated in the younger age group. The 10-µg dose was carefully selected as the preferred dose for safety, tolerability and immunogenicity in children 5 to 12 years of age.
The same data have been submitted to the US Food and Drug Administration (FDA) and will be filed with other regulatory authorities. Pfizer and BioNTech plan to submit data from the full Phase III trial for scientific peer-review publication.
A briefing document posted by the FDA read: “FDA conducted a quantitative benefit-risk analysis to evaluate predicted numbers of symptomatic Covid-19 cases, hospitalisations, ICU admissions, and deaths that would be prevented per million fully vaccinated children 5-11 years of age over a 6-month period, as compared with predicted numbers of vaccine-associated excess myocarditis cases, hospitalisations, ICU admissions and deaths per million fully vaccinated children 5-11 years of age. The model conservatively assumed that the risk of myocarditis/pericarditis associated with the 10 µg dose in children 5-11 years of age would the same as the estimated risk associated with the 30 µg dose in adolescents 12-15 years of age from Optum healthcare claims data. While benefits of vaccination were highly dependent on Covid-19 incidence, the overall analysis predicted that the numbers of clinically significant Covid-19-related outcomes prevented would clearly outweigh the numbers of vaccine-associated excess myocarditis cases over a range of assumptions for Covid-19 incidence. At the lowest evaluated Covid-19 incidence (corresponding to the June 2021 nadir), the predicted number of vaccine-associated myocarditis cases was greater than the predicted number of Covid-19 hospitalisations prevented for males and for both sexes combined. However, in consideration of the different clinical implications of hospitalisation for Covid-19 versus hospitalisation for vaccine associated myocarditis, and benefits related to prevention of non-hospitalised cases of Covid with significant morbidity, the overall benefits of the vaccine may still outweigh the risks under this low incidence scenario. If the myocarditis/pericarditis risk in this age group is lower than the conservative assumption used in the model, the benefit-risk balance would be even more favorable.”
Image credit: Kelly Sikkema
