By IDSE News Staff
The FDA expanded the emergency use authorization (EUA) of the Moderna COVID-19 and Pfizer-BioNTech COVID-19 vaccines for the prevention of COVID-19 to include use in children down to 6 months of age.
For the Moderna COVID-19 vaccine, the FDA amended the EUA to include use of the vaccine in children 6 months through 17 years of age.
For the Pfizer-BioNTech COVID-19 vaccine, the FDA amended the EUA to include use of the vaccine in individuals 6 months through 4 years of age. The vaccine had been authorized for use in individuals 5 years of age and older.
The FDA’s evaluation and analysis of the safety, effectiveness and manufacturing data of these vaccines were rigorous and comprehensive, supporting the EUAs, the agency said.
The FDA considered the effectiveness and safety data about the Moderna COVID-19 vaccine were generated in two ongoing, randomized, blinded, placebo-controlled clinical trials in the United States and Canada, which enrolled infants, children and adolescents.
The immune responses of a subset of 230 children 6 months through 23 months and a subset of 260 children 2 through 5 years of age who received a two-dose primary series of the Moderna COVID-19 vaccine at 25 mcg of messenger RNA (mRNA) per dose were compared with the immune responses of 290 adults 18 through 25 years who received two higher doses of the vaccine in a previous study, which determined the vaccine to be effective in preventing COVID-19. In these FDA analyses, the immune responses to the vaccine, of both age groups of children, were comparable to the immune responses of the adults.
An analysis of cases of COVID-19 occurring at least 14 days after the second dose among approximately 5,400 children in this age group without evidence of prior infection with SARS-CoV-2 was conducted when the omicron variant was the predominant circulating strain. In this analysis, among participants 6 months through 23 months of age, 64% of whom had blinded follow-up for more than two months after the second dose, the vaccine was 50.6% effective in preventing COVID-19. Among participants 2 through 5 years of age, 72% of whom had blinded follow-up for more than two months after the second dose, the vaccine was 36.8% effective in preventing COVID-19.
The immune responses of a subset of 320 children 6 years through 11 years who received a two-dose primary series of the Moderna COVID-19 vaccine at 50 mcg of mRNA per dose were compared with the immune responses of 295 adults 18 through 25 years who received two higher doses of the vaccine in a previous study, which determined the vaccine to be effective in preventing COVID-19. In the FDA analysis, the immune responses of the children to the vaccine were comparable to the immune responses of the adults. An additional analysis pertaining to the occurrence of COVID-19 cases was determined not to be reliable due to the low number of COVID-19 cases that occurred in study participants.
The immune responses of a subset of 340 adolescents 12 through 17 years of age who received a two-dose primary series of the Moderna COVID-19 vaccine at 100 mcg of mRNA per dose were compared with the immune responses of 296 adults 18 through 25 years who received two equivalent doses of the vaccine in a previous study, which determined the vaccine to be effective in preventing COVID-19. In this analysis, the immune responses of the adolescents were comparable to the immune responses of the older participants.
An analysis also was conducted of COVID-19 cases occurring at least 14 days after the second dose among approximately 3,000 adolescents in this age group without evidence of prior infection with SARS-CoV-2, in which approximately 42% of participants had two or more months of blinded follow-up after the second dose. In this analysis, among participants 12 through 17 years of age, the vaccine was 93.3% effective in preventing COVID-19. The data for this analysis were obtained before the omicron variant became the predominant circulating strain.
The safety data to support the Moderna COVID-19 vaccine EUA in individuals 6 months through 17 years of age are as follows:
- Children 6 months through 5 years of age: Safety was evaluated in approximately 1,700 children 6 through 23 months of age who received the vaccine and 600 who received placebo. Of these, approximately 1,100 vaccine recipients were followed for safety for at least two months after the second dose. For participants 2 through 5 years of age, approximately 3,000 received the vaccine and approximately 1,000 received placebo; approximately 2,200 vaccine recipients were followed for safety for at least two months after the second dose. In clinical trial participants 6 months through 5 years of age, the most commonly reported side effects across all age subgroups included pain, redness and swelling at the injection site, fever, and underarm (or groin) swelling/tenderness of the lymph nodes in the same arm (or thigh) as the injection. In clinical trial participants 6 through 36 months of age, the most commonly reported side effects also included irritability/crying, sleepiness and loss of appetite. In clinical trial participants 37 months through 5 years of age, the most commonly reported side effects also included fatigue, headache, muscle ache, chills, nausea/vomiting and joint stiffness.
- Children 6 through 11 years of age: Safety was evaluated in approximately 3,000 children who received the vaccine and approximately 1,000 children who received placebo. The majority of vaccine recipients (98.7%) had at least two months of safety follow-up after their second dose.
- Adolescents 12 through 17 years of age: Safety was evaluated in approximately 2,500 participants who received the vaccine and 1,200 who received placebo. The majority of vaccine recipients (95.6%) had at least six months of follow-up after the second dose.
The most commonly reported side effects in the clinical trial participants for both the 6 through 11 age group and the 12 through 17 age group who received the vaccine included pain, redness and swelling at the injection site, tiredness, headache, muscle pain, chills, joint pain, underarm swelling of the lymph nodes in the same arm as the injection, nausea and vomiting, and fever.
The Pfizer-BioNTech Data
The effectiveness and safety data evaluated and analyzed by the FDA for the Pfizer-BioNTech COVID-19 vaccine were generated in an ongoing, randomized, blinded, placebo-controlled clinical trial in the United States and internationally, which enrolled infants and children.
The effectiveness data to support the EUA in children 6 months through 4 years of age are based on a comparison of immune responses following three doses of the Pfizer-BioNTech COVID-19 vaccine in a subset of children in this age group to the immune responses among adults 16 through 25 years of age who received two higher doses of the Pfizer-BioNTech COVID-19 vaccine in a previous study, which determined the vaccine to be effective in preventing COVID-19. The study was conducted in two age subgroups. The immune responses to the vaccine of approximately 80 children, 6 through 23 months of age, and approximately 140 children, 2 through 4 years of age, were compared with the immune responses of approximately 170 of the older participants. In these FDA analyses, the immune responses to the vaccine for both age groups of children were comparable to the immune responses of the older participants. An additional analysis pertaining to the occurrence of COVID-19 cases was determined not to be reliable due to the low number of COVID-19 cases that occurred in the study participants.
The available safety data to support the EUA in children 6 through 23 months of age include approximately 1,170 who received the vaccine and approximately 600 who received placebo; approximately 400 vaccine recipients were followed for safety for at least two months after the third dose. For the participants 2 through 4 years of age, approximately 1,800 received the vaccine and approximately 900 received placebo; approximately 600 vaccine recipients were followed for safety for at least two months after the third dose. The most commonly reported side effects in the clinical trial participants 6 through 23 months of age who received the vaccine were irritability; decreased appetite; fever; and pain, tenderness, redness and swelling at the injection site. These side effects were also reported for the vaccine recipients 2 through 4 years age, in addition to fever, headache and chills.
Risk for Myocarditis and Pericarditis
The FDA and CDC safety surveillance systems have identified an increased risk for myocarditis and pericarditis following vaccination with the Moderna COVID-19 and Pfizer-BioNTech COVID-19 vaccines, particularly after the second dose. The observed risk is highest in males 18 through 24 years of age for the Moderna COVID-19 vaccine and in males 12 through 17 years of age for the Pfizer-BioNTech COVID-19 vaccine.
The FDA and CDC analyses of available safety surveillance data from the United States and other countries on myocarditis outcomes continue to strengthen the evidence that most cases of myocarditis associated with the Moderna and Pfizer-BioNTech COVID-19 vaccines are characterized by rapid resolution of symptoms following conservative management, with no impact on quality of life reported by most patients who were contacted for follow-up at 90 days or more after reporting myocarditis. The risk for myocarditis and pericarditis is described in the fact sheets for each of these vaccines.
The FDA determined that the known and potential benefits of the two vaccines outweighed the known and potential risks in the pediatric populations authorized for use for each vaccine.
Prior to making the decision to authorize these vaccines for the respective pediatric populations, the FDA’s independent Vaccines and Related Biological Products Advisory Committee voted in support of the authorizations.
“Many parents, caregivers and clinicians have been waiting for a vaccine for younger children, and this action will help protect those down to 6 months of age. As we have seen with older age groups, we expect that the vaccines for younger children will provide protection from the most severe outcomes of COVID-19, such as hospitalization and death,” said FDA Commissioner Robert M. Califf, MD. “Those trusted with the care of children can have confidence in the safety and effectiveness of these COVID-19 vaccines and can be assured that the agency was thorough in its evaluation of the data.”
The Moderna COVID-19 vaccine will be administered as a primary series of two doses, one month apart, to children 6 months through 17 years of age. The vaccine is also authorized to provide a third primary series dose at least one month after the second dose for individuals in this age group who have been determined to be immunocompromised.
The Pfizer-BioNTech COVID-19 vaccine will be administered as a primary series of three doses in which the initial two doses are administered three weeks apart followed by a third dose administered at least eight weeks after the second dose in individuals 6 months through 4 years of age.
The CDC's Advisory Committee on Immunization Practices will review the recommendation and decide whether these recommendations should be added to the vaccine schedule. They are meeting June 17-18.
