Pfizer and the FDA announced today that they would postpone their review of vaccines for kids under 5. The statement they gave is linked here. The key parts:
The U.S. Food and Drug Administration has been notified by Pfizer that new data have recently emerged regarding its emergency use authorization request for the use of the Pfizer-BioNTech COVID-19 Vaccine in children 6 months through 4 years of age. As part of its rolling submission, the company recently notified the agency of additional findings from its ongoing clinical trial. Based on the agency’s preliminary assessment, and to allow more time to evaluate additional data, we believe additional information regarding the ongoing evaluation of a third dose should be considered as part of our decision-making for potential authorization.
Therefore, the FDA is postponing the Vaccines and Related Biological Products Advisory Committee meeting originally scheduled for Feb. 15. This will give the agency time to consider the additional data, allowing for a transparent public discussion as part of our usual scientific and regulatory processes for COVID-19 vaccines. We will provide an update on timing for the advisory committee meeting once we receive additional data on a third dose in this age group from the company’s ongoing clinical trial and have an opportunity to complete an updated evaluation.
I had intended to write today about the trial. Now there’s not as much to say, but let me try to explain what we know and maybe try to talk you off the ledge.
December
As a reminder and overview, Pfizer has run its vaccine trials in four tranches. First, the company ran a trial of a 30-microgram vaccine dose in adults. This was successful, and the vaccine for that group was approved in December 2020. Second, it extended that same dose down to children ages 12 to 15.
Third, it tested a dose of 10 micrograms in children 5 to 11. In this group, the target goal was antibody levels — the study was what is called “immune-bridging.” Because serious illness is much less common in this group than in adults, and because the trial was small, the focus was on showing a robust antibody response to the vaccine. The trial found this, and in addition found evidence of a very large (about 90%) reduction in risk of symptomatic illness. I wrote about that. The vaccines for this group of children were approved, and the extensive safety data collected post-approval is very reassuring.
Fourth, Pfizer ran a trial at an even lower dose — 3 micrograms — in children six months to 4 years and 11 months. This was, again, an immune-bridging study. The hope was to have submission to the FDA for approval under an emergency use authorization (EUA) as soon as January. However, in December, the company announced a delay. Although the researchers saw a strong immune response in the age group six months to 24 months, in the children who were 2, 3, and 4 years old, they didn’t see the antibody response that they were targeting.
At the time, Pfizer reported plans to do a third dose — at the same dosing level — in both age groups, with the goal of inducing a greater antibody response. Results and submission based on this data were expected in the spring.
Two Weeks Ago
Then, a couple weeks ago, Pfizer indicated that the FDA had asked the company to submit its documents now and request approval for the two-dose series, with the expectation of a third dose being added later. It was unclear what had happened to prompt this. Rumblings over the following week suggested that the higher case rates during Omicron had allowed the researchers to look directly at illness in children, with possibly promising results.
They planned to evaluate the data February 15th, with an aim of starting doses the week of Feb 21st.
Today
The FDA was supposed to post the “Panel Pack” today. Instead, they posted a statement postponing the meeting. There were “additional findings” as part of the submission and they are waiting for the third dose information until discussing. So, we are back to where we were in December.
WTF is Going on?
I don’t know, and I’m not sure anyone else outside the room really does either. There are really two options. One is that something emerged in the data review that was concerning. I think this is very unlikely, in part because Pfizer expressed confidence in approval after sending in the submission.
Instead, what I think is likely is that — as we knew in December — the two-dose series did not provide a very strong immune response in the 2 to 5 year olds. The rumblings about efficacy against symptomatic illness suggested a 50 to 60% reduction in illness risk, and that this was lower with Omicron than with Delta. This would be a reasonable but not amazing efficacy level.
At the same time, especially with the milder variant and the ebbing of the Omicron wave, the risks to young children are small. Serious illness is rare in this group, even without a vaccine. Given that, there was likely to be concern about issuing an EUA. Effectively, the FDA may have found themselves contemplating approving a vaccine with somewhat limited efficacy against a threat which is limited in this age group.
As they contemplated this, they likely faced significant push back, internally and externally. My best — totally speculative — guess is that they were concerned that the EUA would be rejected by their panel, and this would be embarrassing and damaging. So they pulled the plug.
I cannot emphasize strongly enough what a complete messaging and public relations fiasco this is. Whether it is appropriate to approve the vaccine at this phase or not, I cannot say. What I can say with 100% certainty is that this is about the worst possible way the process could have been run.
What do I do now?
First: timing-wise, Pfizer has said their third dose data will be available in early April. At this point, it’s hard to say what will happen.
Second: please try not to despair.
Third: take a data breath. The risk of COVID to the vast majority of young children is extremely low. It is lower than many other risks — the flu, RSV, driving. The reality is that even with a vaccine, your child is going to get COVID at some point in their lives, if they have not had it already. If your child has already had COVID, they’re as well protected as if they had the vaccine. In most places in the country, Omicron is waning and the next weeks are likely to look better than the last. This lowers the risk even further.
So while I totally get the desire to feel the safety of the vaccine — I really do – the magnitude of the reduction in illness risk is very, very small.
Fourth, and hardest, and not for today perhaps: Think about moving forward without this. Yes, Pfizer might apply in April and this might be approved. But it might not. It may be time — even if you have unvaccinated kids — to consider the next phase of the pandemic. I sense that at least some of you are waiting for the vaccine as an “end”. It may be time to decide you are ready to move forward — baby steps first — even without a shot for now.
For policymakers: a plea. If you are not going to approve vaccines, please fix the quarantine rules for child care to allow test to stay or something else. It is completely unreasonable and out of the question to continue with the current system for months and months more.
Hang in there. I’ll be back on Monday. Hugs.
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