Pfizer Vax for Young Kids Passes the Test Among FDA Staff

Pfizer-BioNTech’s COVID-19 vaccine produced an immune response and was safe and effective in young children, but its benefits may be largely dependent on severity of the COVID outbreak, according to FDA briefing documents released late Friday.

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) will meet on Tuesday for the third time this month to discuss COVID-19 vaccines, this time to see if the benefits outweigh the risks among children ages 5-11 years.

A two-dose regimen of 10 μg apiece, administered 21 days apart, met immunobridging success criteria, FDA staff said. The agency analyzed data from topline results released in September that found increases in neutralizing antibody geometric mean titers among children ages 5-11 versus individuals ages 16-25, as well as comparable seroresponse rates among the two groups versus baseline.

Adverse events (AEs) were similar to other populations, with no cases of myocarditis or pericarditis, anaphylaxis or deaths among ages 5-11, and this was after data from an additional 1,590 vaccine recipients and 788 participants from the phase II/III trial (called cohort 2). This was per the agency’s request “to allow for more robust assessment of serious adverse events and other adverse events of interest,” FDA staff said.

The manufacturer even included a descriptive efficacy analysis, which made headlines on Friday morning, that found 90.7% vaccine efficacy (VE; 95% CI 67.4-98.3%), with three COVID cases in the vaccine group and 16 in placebo. None of the cases met the criteria for severe COVID.

Interestingly, FDA staff conducted a benefit/risk assessment using several models of both VE and COVID incidence. They found that while “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,” the strength of benefits were varied.

Data was primarily from phase II/III of the phase I/II/III study C4591007, which had 3,109 participants who received vaccine and 1,528 who received placebo. It was made up of two cohorts: Cohort 1, with 1,444 in the vaccine group and 714 in the placebo group, each with at least 2 months of follow-up safety data, and cohort 2, who had a median of 2.4 weeks of follow-up data at the time of data cutoff on October 8.

FDA staff noted, “data verification is in process, but not yet finished at the time this briefing book was completed.”

The study is ongoing, with 70% of the participants from the U.S. They were a mean age of 8 years, 51-53% were boys, and nearly 80% were white. About 12% had obesity, and 21% had comorbidities putting them at risk of severe COVID-19.

About 20% of participants in the descriptive efficacy analysis who acquired COVID-19 had comorbidities, and most infections occurred during July-August 2021.

Examining reactogenicity, the most common AE was fatigue (39%), followed by headache (28%) and muscle pain (12%). Most systemic AEs were mild or moderate, and resolved 1-2 days after onset, FDA staff noted.

The most common unsolicited AE was lymphadenopathy, reported in 13 vaccine participants and one placebo participant, and more vaccine recipients reported hypersensitivity-related AEs, such as rash and dermatitis.

For the benefit/risk assessment, the FDA conducted a series of models that measured symptomatic COVID-19 cases, hospitalizations, ICU admissions, and death compared to excess myocarditis/pericarditis cases, hospitalizations, ICU admissions, and death.

They found that the benefits were highest among kids ages 5-11 in the scenarios using the Delta-surge peak incidence, high VE, and higher COVID death rate, and lowest in scenarios with the lowest incidence.

In this scenario, “the model predicts more excess hospitalizations due to vaccine-related myocarditis/pericarditis compared to prevented hospitalizations due to COVID-19,” FDA staff wrote. “However, in consideration of the different clinical implications of hospitalization for COVID-19 versus hospitalization for vaccine-associated myocarditis/pericarditis […] the overall benefits of the vaccine may still outweigh the risks under this lowest incidence scenario.”

They also pointed out that they used a “conservative assumption” for myocarditis risk, namely healthcare claims from adolescents ages 12-17, and if the risk is lower among younger children, “the benefit-risk balance would be more favorable.”