Strike Two: US FDA Vaccine Advisors Again Shoot Down Broad COVID-19 Vaccine Boosting
Executive Summary
Surprising move to have VRBPAC debate offering mRNA boosters to everyone 18 and up, less than one month after the panel shot that down for Pfizer’s vaccine, thus stalling the White House’s plan for a broad booster rollout, was driven internally by the FDA, a senior health official said.
The US Food and Drug Administration’s vaccine advisors continue to be skeptical of universal boosting of all US adults with mRNA COVID-19 vaccines, but Center for Biologics Evaluation and Research Director Peter Marks indicated he may want to move in that direction anyway.
FDA unexpectedly asked the Vaccines and Related Biological Products Advisory Committee to discuss whether available data support the use of a Pfizer Inc./BioNTech SE or Moderna, Inc. booster dose given at least 6 months after completion of the same mRNA COIVD-19 vaccine primary series in the general population of adults less than 65 years of age at the 14 October meeting that was billed as focusing on Moderna’s booster application. (See sidebar.)
Moderna is seeking an emergency use authorization in individuals 65 years of age and older, and individuals 18-64 who are at high risk of severe COVID-19 or whose frequent institutional or occupational exposure to SARS-CoV-2 puts them at high risk of serious complications of COVID-19 including severe COVID-19.
The indication mirrors the one the VRBPAC and then FDA cleared for Pfizer’s booster, following the VRBPAC’s overwhelmingly negative vote on 17 September against boosting all Pfizer vaccine recipients 16 years of age and older. (Also see "US FDA Panel Rejects Pfizer's Broad COVID Booster Plan But Backs Narrower Authorization For Third Vaccine Shot" - Pink Sheet, 17 Sep, 2021.)
That decision was a slight blow to the Biden administration who had been telegraphing that boosters would be widely available starting on 20 September, despite lingering scientific debate about whether an additional shot is needed by most Americans and the resulting impact such boosting would have on the limited global supply of vaccine for the unvaccinated. (Also see "Biden’s Trump Moment? COVID Booster Messaging Complicated After Top FDA Scientists Raise Doubts" - Pink Sheet, 13 Sep, 2021.)
But a senior health official disputed the notion that politics drove FDA to raise the broader indication with its advisors again so quickly after the failed vote, telling the Pink Sheet that the questions and discussion topics for the 14 October meeting were determined solely by FDA.
More Israeli Data Doesn’t Make A Difference
The main difference between the 17 September meeting and the 14 October one was that Israel health officials had more data from its booster campaign, particularly in younger populations.
But many VRBPAC members continued to have questions about the strength of the Israeli observational data, along with its relevance to the US population.
“I don’t necessarily see the need for a sort of let it rip campaign for boosters” said Michael Kurilla, director of the division of clinical innovation at the US National Institutes of Health’s National Center for Advancing Translational Sciences.
“I was not as impressed with the Israeli data as the justification,” he added. “They may be attributing the profile of their wave to the introduction of boosters, but I think if you look at their first and second waves, which was pre vaccines, they qualitatively looked very similar. And in fact, if you look at the Delta wave that went through India, which has less than 20% fully vaccinated people, that was very similar to what we're seeing here.”
Many felt the companies needed to make a stronger case on both safety and efficacy to justify boosting more broadly.
“I am very concerned about the paucity of data on which this decision would be made,” said Archana Chatterjee, Vice President for Medical Affairs at Rosalind Franklin University.
‘We Lack The Risk-Benefit Analysis Needed’
The studies submitted by both Moderna and Pfizer were done in too small populations given the hundreds of millions of people a broader booster recommendation could impact and the population FDA is proposing seems to be well protected, especially from the most severe forms of disease, from the primary vaccination series, she added.
“We lack the risk-benefit analysis needed to justify giving more vaccine to young people who are not otherwise at risk,” said Eric Rubin, editor-in-chief of the New England Journal of Medicine.
That benefit wouldn’t necessarily have to be directly to the vaccinee, he added. It could be on the inhibition of transmission, for example.
“But we don’t have that. We don’t really have a good idea of the benefits of boosters for this group. And there’s a good reason to think that there isn’t much benefit. And we know that there’s some [safety] signal and I’m not sure that you want to just explore it willy nilly by giving it to a lot of people,” Rubin said.
Many felt that boosting young and healthy people would have little impact on the pandemic’s trajectory.
“I'm impressed by the fact that we continue to have excellent protection against moderate to severe disease in this country, through Delta and for all age groups. And I just think that we continue to send wrong messages out there by using terms like breakthrough and by making people feel that they’re not protected unless they’ve gotten a third dose. … The problem in this country is vaccinating the unvaccinated,” said Paul Offit of the Children’s Hospital of Philadelphia.
Offit pushed federal officials to better define the goal of the COVID-19 vaccine campaign, noting expecting the vaccine to prevent asymptomatic or mild symptomatic infections forever is a bar to which no other vaccine is held.
Overall, Offit said universal boosting “is wrong,” but relented he might “feel a little better” allowing people 30 and up to get boosters, because there is less risk of myocarditis from the vaccines as people get older.
A couple of committee members, including the acting chair Arnold Monto of the University of Michigan, suggested it might be worthwhile to break up the population into narrower age ranges as some closer to 65 years of age might warrant a booster.
This could also address health inequities seen during the pandemic.
“Given the incredible impact COVID has had on many older communities of color, it’s especially important that we protect older persons of color who may not actually meet that 65 age cutoff. And so I would like to consider at least moving down to age 50,” said Amanda Cohn, chief medical officer at the Center for Disease Control and Prevention’s National Center for Immunization and Respiratory Diseases.
FDA Worries About Waiting Too Long
Despite VRBPAC’s reservations about universal boosting, FDA leadership expressed openness to moving in that direction sooner rather than later.
“I think we heard pretty loud and clearly that there was not a lot of appetite for moving down the age range very significantly, if at all,” FDA’s Marks said following the discussion.
But he also worried about the consequences of waiting too long to act.
“The problem here is that we don’t know what we don’t know. And making any predictions about what’s going to happen in in the next month is very challenging. There are models that predict that we could potentially have another wave of COVID-19 as people go inside this winter and we have either the current variants or another one come up. So that is part of what is going into our minds here about being prepared. I think we can’t simply look right now at what’s going on with the pandemic curves and just call it a day, we have to be able to think about what might happen,” Marks said.
Marks’ enthusiasm for interventions against COVID even in the absence of definitive findings can also be seen in his support of convalescent plasma treatment last year. (Also see "Email Trove From US FDA Shows Peter Marks As Champion For Plasma Authorization" - Pink Sheet, 7 Oct, 2021.)
One committee member, Hayley Gans, a professor of pediatrics at Stanford University, seemed to share some of Mark’s concern about the uncertain course of the pandemic.
“It’s true that Delta is dropping. But it’s also true that this is a different disease form and we are seeing people hospitalized, who don’t necessarily meet the risk factors that we understood originally. I think it’s very important not to ignore signals early so that we can cause prevention,” said Gans.