Leading Pfizer Scientist on Vaccine for Kids Under 12

John Whyte, MD; William C. Gruber, MD

Disclosures

August 06, 2021

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JOHN WHYTE: The COVID pandemic has resulted in over 35 million Americans becoming infected and over 600,000 people dying. Vaccines, developed in record time, are helping to control the pandemic, and hopefully ending it soon. Yet, millions of Americans are skeptical. They think the vaccine development program was too fast, or the side effects are too serious and it's too risky, or they just don't know who to believe. I sat down with Dr. William Gruber -- he's Pfizer's senior vice president of vaccine clinical research and development -- where he took on these issues, as well as addressed the questions that are most on your mind.

I want to talk about vaccination in kids under 12.

WILLIAM GRUBER: Yeah.

JOHN WHYTE: Where's Pfizer on these trials in kids less than 12? It's been previously announced that you expect to submit data sometime in the fall. Dr. Fauci recently said he doesn't expect any vaccination in kids under 12 till midwinter. I'm not sure what that counts as.

WILLIAM GRUBER: Yeah.

JOHN WHYTE: So talk to us a little bit about the timeline for vaccination in kids, because parents want to know what is the fall going to look like.

WILLIAM GRUBER: Yeah. So we take, obviously, a very deliberate and serious approach, just as we do for any population, particularly in children to assure safety and efficacy, or an immune response that's likely to predict efficacy of the vaccine. So we took a very deliberate approach, recognizing that, for the mRNA vaccines, there was some tendency to have more reactions in terms of local reactions at the site of injection or systemic reactions, such as fever or chills, in younger age groups.

And so we were very deliberate. When we, for instance, began with the 12- to 15-year-olds, we basically started off with a small number of those individuals to assure ourselves that the safety profile at the 30-microgram dose, which we use in older individuals, would be safe and effective. And it was.

And fortunately, we were gratified that not only did we prove that the vaccine had a safety and tolerability profile and an efficacy profile in the end that supported its use, but it gave us then some confidence, OK, we can take this deliberate approach as we move down, with the recognition, though, that as we move in younger age, that maybe we would actually do just as well with a lower dose. And part of that was driven by the fact that, once we had the 12- to 15-year-old data, we actually saw that the antibody responses -- again, this marker that we think helps predict the likelihood that the vaccine is going to be effective -- in the 12- to 15-year-olds was actually higher than what we saw in even 16- to 25-year-olds.

So in that circumstance, it said, OK, well, we can actually potentially further minimize the local and systemic reactions we see with the vaccine by starting at a lower dose. So we began to look first at 3, 10, 30 micrograms in these younger populations -- so populations between 5 and 11, between 2 and 4, almost 5 years of age, and 6 months to 2 years of age -- and very deliberately moved down in age with low doses, and determining what would be the highest dose that would give us the appropriate sort of safety profile and give us the appropriate sort of immune response, and, vice versa, the lowest dose that would basically give us that, and then worked down in age very deliberately.

We did that with small numbers of individuals, came up with an appropriate dose for the youngest individuals, which worked out to be 10 micrograms for the 5- to 11-year-olds and 3 micrograms for 6 months to 4-year-olds, and have now moved to expanded populations to enlarge our ability to examine the safety, as well as the immune response to that vaccine, which, by the way, we're also capturing cases on the chance that we will actually be able to demonstrate efficacy as part of those trials. And we think that body of information will then lend itself to being confident about the safety profile, as well as the ability to provide protection that we would anticipate to file.

And of course, winter comes early in the Northeast, so I'm thinking, you know, we're still, I think, targeting the October time frame. Obviously, there will be deliberation that occurs after that from the FDA, and ultimately from the ACIP to make recommendation, the Advisory Committee on Immunization Practice at the CDC. But I am optimistic that, before the end of this year, we will actually have an emergency use authorization, if all goes well in terms of the safety and immune response.

JOHN WHYTE: Well, the FDA did announce that it would go to an advisory committee, as opposed to the 12 through 17 authorization did not. So we'll have to see. But you expect to file something in October.

WILLIAM GRUBER: Yeah, yeah. That's our current plan.

JOHN WHYTE: Let's talk about the outcomes that are measured that you referenced to, because in the adult population, we did look at cases in terms of symptomatic cases, hospitalizations, and deaths as the primary endpoint for approval. For children under 12, that would be very difficult, would it not? Because cases, although they occur, do not as often.

We're actually conducting the trial at a time where we're actually seeing improvements in vaccination rates. So how do we know for sure that it meets the safety and efficacy standard for children, who many people argue are developing their immune systems? There's some impredictability based on that. How do we feel confident that we know that it's safe and effective for kids under 12?

WILLIAM GRUBER: Yeah, so I think, first of all, I would go to the precedent for other vaccines, where we've developed them often in adults and moved down to children, and shown that the safety profiles and immune response profiles and efficacy profiles in adults and working down to children has reliably predicted the safety profile in young children. And then as I mentioned before, presuming we get emergency use authorization, the story's not over there for us, nor is the work done.

We continue in a post-licensure environment to capture information in that population of children to better document the nature of the full, comprehensive safety profile and the potential for efficacy. You're right in that these small numbers, we may or may not be able to demonstrate efficacy in the course of the current trends. But again, we don't want to hold hostage the potential to really provide an important benefit to children, to allow them to go back to school, to be able to resume normal activities, to allow families to essentially not worry about the potential for spread from that child into the home or that child ending up ill enough to end in the hospital.

So I think it's really that balance. And we've worked very rigorously with the FDA to be able to evaluate the nature of the immune response to be confident that the immune response that we in children, based on we've seen in efficacy in other populations, that that immune response will likely predict the same level of efficacy. And of course, then, the safety profile will speak for itself, in terms of the common reactions, as well as, as the numbers increase, the rare reactions.

JOHN WHYTE: But we know that the incidence in kids less than 12 is on the low side. We do know when they get it, it's less severe. Granted, some children have died in this age group of COVID. There are some people out there saying they shouldn't qualify for emergency use based on the definition of a public health emergency in that age group. What do you say to those persons, who say, Dr. Gruber, we need to wait, and I don't want my kids to be one of the first people to get it? How do you reassure them?

WILLIAM GRUBER: Yeah, well, I think the best example I can give is what we do in the clinical trials, because they're the first people to actually line up. And I will say that, perhaps more so than for most any other pediatric trial I've done, there is pent-up demand, where in fact we have more people volunteering for trials than actually we can accommodate in the trial. Now, why is that? I think it's because of a number of things.

Number one, there is a recognition that, as time goes on, as we have become more and more successful in preventing adult disease, the only individuals we're likely to see are going to be the unvaccinated, which includes children, right? And so they will -- and we already know, I mean, you can hear from ACIP members, you know, when they've talked about the need for a pediatric vaccine. So I think there's pent-up demand to essentially help the child themselves and reduce that risk of hospitalization, but also just the notion of freeing up children so they can go back to school.

There's been a great loss, I think, in the past year. And I think you hear this from pediatricians and individuals involved in education, where many children are now behind because of the virtual sorts of learning environments that they were subject to during the past year. It's important to have children back in school, and one of the best mechanisms to make that possible is to provide protection to them so they cannot either experience the disease themselves or spread it to others.

It's important for children at all ages. If you think about it, it's not just the educational aspects, it's the social aspects. It's the ability to engage -- and I'm thinking particularly of adolescents, in terms of sports activities, drama club, the other sorts of things that enrich children's lives and help them develop. So I would say --

JOHN WHYTE: Were you in drama club?

WILLIAM GRUBER: No, but I was in debate. So I think the notion is that we need to get back and out of our cocoons. It's been liberating for adults to be removed from many of the restrictions that we've all had to endure over the past year. How can it be any more important in adults than it is in children? It's going to be incredibly important to do that for children.

JOHN WHYTE: And finally, what do you say to viewers who say, “Dr. Gruber, what you said is great, but I'm still just not sure”?

WILLIAM GRUBER: I would say get as much information as you can. Talk to individuals that you trust to give you good guidance, whether it's clergymen, your physician, community leaders. And learn the facts and make a decision. And I think, on balance, if you do that, you'll make a decision that the vaccine is right for you.

JOHN WHYTE: That's good advice. Dr. Gruber, thanks for taking the time today.

WILLIAM GRUBER: OK, thank you.

This interview originally appeared on WebMD on August 06, 2021

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