FDA Advisors Leave Door Open To Mix and Match COVID-19 Vaccine Boosters
Executive Summary
Discussion also reopened the debate on allowing universal boosting with mRNA vaccines, with advisors giving FDA more leeway to allow some younger Americans to get an additional mRNA shot regardless of their occupation or underlying health conditions.
Some of the US Food and Drug Administration’s vaccine advisors seemed comfortable with permitting the agency to allow heterologous boosting of COVID-19 vaccines at a 15 October meeting, with a few expressing an urgency for the decision to be made, likely giving the agency enough support to move forward with an adjustment to the relevant emergency use authorizations without additional data.
The Vaccines and Related Biological Products Advisory Committee heard a presentation on study results from the National Institutes of Health on 15 October that suggested potential benefits to using a different vaccine for the booster to better increase antibody response, particularly for those who received Johnson & Johnson’s adenovirus COVID-19 vaccine. (Also see "NIH Mix and Match Study Suggests mRNA COVID Vaccines May Offer Stronger Boost Than J&J" - Pink Sheet, 13 Oct, 2021.)
They weren’t asked to formally vote on heterologous boosting as FDA itself hadn’t had time to fully review the data, but instead were asked to weigh in on the data they would want to see to support an emergency use authorization for mixing and matching. This was a revision to the formal discussion question FDA had planned for the topic that would have only had them comment on observations that could be made from the NIH data. (Also see "Mix and Match COVID Boosters: Time Crunch For Data Review May Mean No Advisory Committee Vote" - Pink Sheet, 7 Oct, 2021.)
The nature of the discussion format meant not all 19 committee members weighed in on the topic. Among those who did there was a split between panelists who pushed for more data ahead of FDA clearance of heterologous boosting, and those who were ready to permit it now, with the latter group slightly outnumbering the former.
Many who supported permitting heterologous boosting now made a pragmatic argument for acting imminently.
“I think that that from a public health perspective, there’s a clear need in some situations for individuals to receive a different vaccine,” said Amanda Cohn, chief medical officer at the Center for Disease Control and Prevention’s National Center for Immunization and Respiratory Diseases, noting that some individuals vaccinated with J&J’s vaccine may have difficulty obtaining access to a second shot of the product and that others may want to choose a different vaccine combination due to particular safety preferences.
For example, a younger male may choose to avoid mRNA vaccines due to the risk of myocarditis, while a younger female might be concerned about the risk of thrombosis with thrombocytopenia syndrome with J&J’s vaccine. (Also see "Janssen’s COVID-19 Vaccine Should Continue To Be Available, CDC Panel Concurs" - Pink Sheet, 22 Jul, 2021.)
For facilities like nursing homes, being able to use one vaccine as a booster regardless of the primary series patients received would make administrative much easier, Cohn added.
“I'm sold already. And that's because I agree completely with Dr. Cohn’s comment that we need flexibility and improved access for everybody which, the flexibility of being able to mix and match will allow,” said Mark Sawyer, a pediatric infectious disease specialist at the University of California, San Diego. While he felt it was important to collect additional data, he said “the sooner we let this happen in the most straightforward way, the better off we are.”
Hayley Gans, a professor of pediatrics and infectious diseases at Stanford University Medical Center, also asked FDA to move in “rapid fashion,” on the issue.
Archana Chatterjee, vice president for medical affairs at Rosalind Franklin University, said it is particularly important to allow people who might have had an allergy to one vaccine to get a boost with another. However, she asked for more data on the longevity of the boosted antibody response, along with data on heterologous boosting in children, and more data on mix and matching shots in minorities.
There was a range of requests for additional data that spanned both safety and efficacy concerns.
Eric Rubin, editor in chief of New England Journal of Medicine, said he felt the efficacy data provided by NIH was fairly sufficient, but would want a bit larger safety database, at least equivalent to the databases used for the homologous booster EUAs.
Meanwhile, Michael Kurilla, director of the division of clinical innovation at the National Center for Advancing Translational Sciences at the NIH, worried that there has been too much focus on antibody response and neutralizing titers, and not enough on the role of cellular immunity, given that the vaccines still show protection in the absence of neutralizing titers and there is no correlate of protection for COVID vaccines.
He suggested relying on the NIH study, which focuses on measuring antibody response post boost, might not lead to favoring the best regimens when data on cellular immunity is taken into account. Kurilla, suggested that heterologous boosting could be determined by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices once FDA fully licenses all of the vaccines.
Mixing And Matching Revives Conversation On Universal Boosting
The debate over heterologous boosting on 15 October led to an extension of the committee’s previous day’s discussion on whether all adults in the US should be able to get an mRNA booster shot that corresponds to the mRNA primary series they received. (Also see "Strike Two: US FDA Vaccine Advisors Again Shoot Down Broad COVID-19 Vaccine Boosting" - Pink Sheet, 14 Oct, 2021.)
Acting Committee Chair Arnold Monto of University of Michigan and Jeannette Lee, University of Arkansas for Medical Sciences, worried people would be confused if mixing and matching was allowed but all adults who received J&J vaccines were eligible for boosters and only some adults who received Pfizer Inc. or Moderna, Inc.'s mRNA vaccines were eligible for boosters. (Also see "Moderna's COVID-19 Vaccine Booster US FDA Panel Nod Driven By Pragmatism" - Pink Sheet, 14 Oct, 2021.)
FDA’s Center for Biologics Evaluation and Research Director Peter Marks indicated he felt compelled by the Israeli data on boosting to allow mRNA boosters for people age 40 and up regardless of their occupation or underlying health status and asked the committee members about their comfort level with that recommendation – instead of the 18 and up question they were asked the previous day. A few committee members on 14 October had indicated they might be ok with more permissive boosting in older populations less at risk of myocarditis.
The revival of the topic led some additional committee members to express more willingness to open up the mRNA booster population a bit further than they had been the day before if it was constrained by the higher age bracket.
It will need to be done carefully, though, cautioned, Stanley Perlman, of University of Iowa, as he worried the public gets confused and loses trust in public health authorities when they see the “rules changing all the time.”