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The benefits of Novavax's adjuvanted protein-based COVID-19 vaccine outweigh the risks, the FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) said in a near-unanimous vote on Tuesday.

With 21 members voting yes, and one abstention, VRBPAC recommended Novavax's two-dose vaccine for adults, saying that it met the criteria for FDA emergency use authorization (EUA).

Members felt that despite a lack of vaccine data against Omicron or longer-term data about waning immunity, as well as some evidence of increased risk of vaccine-associated myocarditis, the data showed that the vaccine was safe and effective, similar to the mRNA vaccines first authorized over a year and a half ago.

At the beginning of the day, however, some members questioned why there was a need for a fourth COVID vaccine for adults, given that Pfizer's vaccine (Comirnaty) and Moderna's vaccine (Spikevax) were not only authorized, but now approved for this population.

Peter Marks, MD, PhD, director of FDA's Center for Biologics Evaluation and Research, characterized the need for a non-mRNA vaccine, given recent limitations with Johnson & Johnson's vaccine, as "filling an unmet need."

"Having a protein-based alternative ... may be more comfortable for some in terms of their acceptance of vaccines," he said. "Anything we can do to get people to accept life-saving medical products is something ... we are compelled to do."

While VRBPAC agreed about the unmet need, some members were skeptical that a fourth COVID vaccine would have any population health effect on vaccine hesitancy. Consumer representative Jay Portnoy, MD, of Children's Mercy Hospital in Kansas City, noted that issues among the vaccine hesitant are usually "more ideological than technological."

Members looked at data from Novavax's phase III study, which included 25,657 adults randomized 2:1 to vaccine or saline placebo. Most participants were from the U.S., though 6% were from Mexico. Median age was 47, three-quarters were white, and a little over a third had obesity. About 12% of both vaccine and placebo groups were adults ages 65 and up.

Vaccine efficacy was 90.4% (95% CI 83.8-94.3) among all participants, though it was slightly lower among the nearly 3,000 older adults in the study (78.7%, 95% CI -16.64 to 96.08).

All members agreed that this was compelling, though Bruce Gellin, MD, of the Rockefeller Foundation in Washington, D.C., abstained from the vote, saying he wanted to vote a "conditional yes," but was not given the opportunity to do so.

Gellin reiterated that he was not voting against the vaccine, but his vote was based on the paucity of additional data reviewed by the FDA, not only against Omicron, but in terms of waning efficacy.

His vote reflected "insights into its performance, not just the science that tells us about its promise," he said, adding that "this vaccine has incredible potential and a lot has been learned about it that we didn't hear about."

Safety was also top of mind throughout the discussion, as post-marketing safety data from other countries found a "potential safety signal" for myocarditis and pericarditis, with 29 reports of pericarditis and four reports of myocarditis. There were also six cases of myocarditis or pericarditis in the manufacturer's clinical safety database, including five that occurred fewer than 20 days after vaccination.

Paul Offit, MD, of Children's Hospital of Philadelphia, emphasized the need to pinpoint the mechanism of vaccine-associated myocarditis, given that the data were "similar to mRNA vaccines." He wondered if perhaps this might be a class effect from all types of COVID vaccines.

"It's incumbent upon us to know if this is about the protein itself or the way the protein is being processed," to help make safer vaccines in the future, he said.

But FDA and committee members disagreed about the necessity of a warning for vaccine-associated myocarditis. Doran Fink, MD, PhD, of the FDA, said that regulatory criteria for a warning is "reasonable evidence of a causal relationship," and the evidence for Novavax was not as extensive as that for mRNA vaccines.

However, Archana Chatterjee, MD, of Rosalind Franklin University of Medicine and Science in Chicago, pointed out that myocarditis was not a concern when mRNA vaccines were initially authorized and it only became evident after more extensive use.

"I'm in favor of this language being included, so providers can be aware of the risk," she said.

Another issue raised by Ofer Levy, MD, PhD, of Boston Children's Hospital, was the "pecking order" of COVID vaccines, and where Novavax might fit in. Marks said that CDC's Advisory Committee on Immunization Practices (ACIP) would take up that issue when they met about this vaccine in the coming days.

The FDA does not have to follow the advice of its advisory committees, but it often does.

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