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In today’s AMA Update, AMA Board Chair Sandra Fryhofer, MD, AMA’s liaison to the Advisory Committee on Immunization Practices (ACIP), and a member of ACIP’s COVID-19 Vaccine Workgroup, recaps the latest news from the U.S. Food and Drug Administration (FDA) Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting. Topics include the vote on “harmonizing” strain composition for both COVID-19 primary vaccines and booster shots, as well as an update about the preliminary stroke risk signal for seniors who received a Pfizer booster. AMA Chief Experience Officer Todd Unger hosts.
- Sandra Fryhofer, MD, chair, AMA Board of Trustees; AMA’s liaison, Advisory Committee on Immunization Practices (ACIP)
Unger: Hello and welcome to the AMA Update video and podcast. Today, we have a slew of COVID updates. Number one, when will we need another COVID booster, highlights from the FDA's Vaccine and Related Biologics Advisory Committee, also known as VRBPAC and an update about the preliminary stroke risk signal for seniors who received a Pfizer booster, and finally, the fall of Evusheld and what it means for immunocompromised patients.
I'm joined today by the AMA Board Chair Dr. Sandra Fryhofer, who's also the AMA's liaison to ACIP, the CDC's Advisory Committee on Immunization Practices, and a member of ACIP's COVID-19 Vaccine Workgroup. I'm Todd Unger, AMA's chief experience officer in Chicago. Dr. Fryhofer, welcome back.
Dr. Fryhofer: Thanks for having me, Todd.
Unger: Let's start first with details about VRBPAC, the meeting that was just held. Who was there and what was on the agenda?
Dr. Fryhofer: Well, VRBPAC is FDA's independent advisory committee, and they met for nine hours on Thursday, January 26. There were presentations by CDC, FDA and by three vaccine manufacturers, Moderna, Pfizer and Novavax were all there. The themes of the day were harmony and simplification for vaccine composition, vaccine dosing schedules and new vaccine development.
COVID infection has now transitioned from pandemic to endemic and FDA is now trying to add structure and organization to a vaccine development and implementation process that's been fast-moving and remarkably successful but somewhat chaotic. Earlier in the week, FDA released a summary briefing and specified topics for vote and also topics for discussion.
Unger: Well, let's talk about that vote. What was it for? And how did it go?
Dr. Fryhofer: The advisory committee voted unanimously in favor of harmonizing vaccine strain composition for all COVID vaccine platforms and for all vaccine doses, including both primary and booster doses. For now, that would mean using the updated bivalent vaccine, which is half original strain and half BA.4/BA.5, for all products and for all doses administered.
Both Pfizer and Moderna already have bivalent vaccines available and authorized in the U.S. Novavax does not. Novavax representatives were there and they did say that the company was prepared to deliver them for the 2023-2024 vaccination season.
Unger: In all of the AMA Updates we've done, I've never heard that term—harmonizing—but I totally understand the impact of harmonizing and simplicity. So let's talk a little bit about how that vaccine composition would be selected. What are the challenges in doing something like that?
Dr. Fryhofer: Well, the SARS-COV-2 virus continues to evolve and spread in a somewhat unpredictable manner. Omicron became dominant in late 2021, but now it has sublineages with various mutations, as well as co-infection recombinations.
The variants which dominate differ across the U.S. and in different parts of the world. So what's circulating here locally is not necessarily what's dominant nationally or internationally. And unlike for flu, there's not a global system in place for monitoring COVID variants.
Now, you may have seen recent news headlines that CDC is actually considering wastewater surveillance at airports to collect more data about emerging variants and also help track new variants entering the U.S. We must continue close surveillance, looking for variants of concern. We also have to monitor vaccine-induced cross-protection.
Unger: Well, when would this kind of vaccine selection process take place? And does it mean that we're going to likely be getting a COVID vaccine each fall, kind of like the flu shot?
Dr. Fryhofer: That's what everybody wants to know. But FDA proposed a system that's very similar to what we do for flu—reviewing data for COVID variants in the spring, announcing any COVID vaccine strain changes in June, with updated vaccines available in the fall.
Now, committee members were quick to remind that COVID is not flu. But FDA's Dr. Peter Marks supported the concept of giving COVID boosters in the fall as a tag-along to the already established seasonal flu vaccine campaigns and as a way to keep hospitals already challenged by flu and RSV from being further overwhelmed by COVID.
We also have to be ready for a worst case scenario if a more pathogenic vaccine escape variant starts circulating, and that would likely trigger an emergency meeting and an ad hoc vaccine strain selection, like what we had to do for flu during the H1N1 pandemic.
The advisory committee was not ready to commit now to a yearly COVID boost as part of a new normal. Only time surveillance and more data will tell. But from the discussion I heard, it does seem pretty likely that a booster will be recommended in the fall of 2023. But after that, who knows? Again, committee members were not ready to commit at this time to yearly COVID vaccinations for the long-term.
Unger: And we'll keep everybody updated on that as things develop. Dr. Fryhofer, one of the, I guess, questions would be, can vaccine makers—those companies—meet the deadlines for something like this within the timeframes? Obviously, you've got to work back from a date like that in the fall, which is strangely not that far away when you think about it.
Dr. Fryhofer: Well, that's a great question. And fortunately, since the vaccine manufacturers were there, they could respond. Pfizer said they could deliver a new vaccine with 100 days notice. Moderna's rep also supported the FDA proposal. Novavax indicated that they would like more of a head start and would prefer a change notification in March rather than June. Again, these are just discussions. Nothing has been set in stone.
Unger: I guess we should not take for granted these modern miracles of vaccine development in terms of those timeframes. But back to the idea of simplicity and trying to harmonize all these different approaches, you mentioned a discussion about standardizing the dosing. So how did that aspect of this go?
Dr. Fryhofer: We're now at a different place. We now have hybrid immunity—immunity from vaccination and immunity from prior infection. And some people have both. According to FDA's review, at least two exposures to the spike protein, through vaccination and/or by infection, provide a degree of protective immunity.
So most people probably only need one vaccine dose to restore protective immunity. However, others may need more. For example, older patients, those with immunocompromising conditions and younger children, especially those not previously immunized, might need two doses or maybe more. The size of the dose would still vary by age group. But standardizing vaccine products in this way would greatly simplify the vaccination schedule.
Committee members pointed out the need for more data and reminded that Pfizer's primary series for the littlest ones, those six months to four-years-old, requires three shots. More data is needed and perhaps we need to right-size those doses as part of that study.
Unger: Well, Dr. Fryhofer, we now have a little bit of time under our belts with the bivalent vaccine. How is that working now against those variants that are circulating out there? And should the vaccine composition change now, and if so, how would we do that?
Dr. Fryhofer: Well, the good news is it seems to be doing pretty well. FDA outlined multiple studies from vaccine manufacturers and from independent researchers indicating better neutralizing antibody response against circulating Omicron variants after a bivalent boost versus a monovalent vaccine dose. FDA review also highlighted observational data that current bivalent boosters provide additional protection against symptomatic infection or emergency department and urgent care visits and hospitalization.
A CDC study published in MMWR and released the day before the meeting shows the bivalent booster does provide additional protection from symptomatic infection with XBB.1.5. In fact, it seems to protect against XBB.1.5 about as well as it does against BA5. But what variant is next?
Most of the focus so far has been on titers of neutralizing antibodies. mRNA vaccine platform is a new vaccine platform. How do these vaccines affect B cells and T cells? What kinds of T cells are produced? Are they CD4 or CD8? Well, several committee members said we shouldn't just be chasing variants.
We need more research as to how these vaccines work. We need more correlates of protection. We need to know more about their impact on long-lasting immunity and this requires more in-depth study. The bottom line, the current bivalent booster is working well against circulating strains. We just need to encourage more people to get it.
Unger: Absolutely. That's good news. And you're absolutely right in terms of having people take advantage of the booster that's out there right now. Should any changes be required, how would they go into effect?
Dr. Fryhofer: Well, as an advisory committee, VRBPAC is just that. It can advise. It can make recommendations. But FDA is the decider. Any change requires FDA action change and authorization or approval. FDA has asked for input from the advisory committee. They got it. Now the ball is in FDA's court.
Unger: Last week, we talked about this issue regarding a signal that came from one of the platforms—the safety platforms—that showed an increased risk of stroke for those that were 65 and older who received a dose of the Pfizer booster. Dr. Fryhofer, can you update everybody on what's transpired since then?
Dr. Fryhofer: Well, CDC said this preliminary signal that was seen only in CDC's vaccine safety datalink seems to have attenuated substantially. The safety concern had not signaled the previous week for the first time. And the signal still has not shown up in any other vaccine safety platform here or in other countries. So that's all good news.
However, a small subanalysis suggests that those who received both the Pfizer booster and a high dose or adjuvanted flu shot at the same time seemed to have a higher risk of stroke. FDA and CDC are looking into this further. They have been very transparent about sharing this information with the public. So more to come on that.
Unger: Thank you so much. And we'll keep everybody updated as we learn more. Let's switch topics slightly to Evusheld and talk about what's happened there. It's been pulled. The FDA has withdrawn its authorization. What's the reasoning behind that move? And how does it affect those with immunocompromised conditions?
Dr. Fryhofer: Well, this is really sad. It's very concerning. Evusheld, as you know, is a combination of two monoclonal antibodies. And it was authorized for COVID pre-exposure prophylaxis for immunocompromised patients back in December of 2021. As of January 20, more than 90% of circulating variants, specifically Omicron's BQ and XSB sublineages are not susceptible to it.
So Evusheld doesn't protect against them. That's why, on January 26, FDA revised its authorization, and, as you said, essentially pulled the plug, because it's no longer effective, at least for now. Now, that could change as the virus changes. So if you have any unexpired Evusheld doses, don't discard them yet. Stay tuned for more updates.
Those who received Evusheld in the past need to know it no longer works. And as I said, this really puts immunocompromised patients in a pickle. On January 27, the CDC published a special information guide in MMWR for patients with immunocompromising conditions and their physicians, urging them to proactively create a COVID-19 action plan.
Physicians and their patients need to know about the therapeutic options, like oral Paxlovid, Remdesivir infusions, and if those aren't available, oral Molnupiravir, and how to get them. Use of convalescent plasma has also been authorized. As you know, there are many drug interactions for Paxlovid. So taking a look at your patient's current medications and figuring out ahead of time any changes that would need to be made if the patient did get COVID could streamline future treatment.
Also, have test kits readily available so your patients can test promptly and you can act fast. In addition to being up to date on vaccines, CDC also recommends additional prevention measures for these immunocompromised patients—patients with immunocompromising conditions—including masking, distancing, improved ventilation, and, of course, washing your hands often.
Unger: Yes, and just like so many things out there, having a plan like that, especially for these high-risk patients, makes so much sense. Dr. Fryhofer, there's been a lot of updates, a lot of activity here. Any final thoughts to wrap this up? ger
Dr. Fryhofer: Well, simplification of the current COVID vaccination process is greatly needed. And discussions at this FDA advisory committee meeting confirmed the importance of getting a dose of the updated Omicron bivalent COVID vaccine. The current bivalent booster is working well against circulating variants. It works well against XBB.1.5. We need to encourage more people to get it.
Unger: Well, that wraps up today's episode. Dr. Fryhofer, thank you for being here today and sharing all of the latest information. We'll be back soon with another AMA Update. Find all our videos and podcasts at ama-assn.org/podcasts. Thanks for joining us. Please take care.
Disclaimer: The viewpoints expressed in this video are those of the participants and/or do not necessarily reflect the views and policies of the AMA.