'Science at its hardest': FDA panel recommends incorporating omicron variant into future COVID boosters

Advisers to the FDA have voted to recommend incorporating a component of the omicron variant into future COVID booster shots, as manufacturers including Pfizer and Moderna await a final ruling from the agency before rolling out new formulations.

The 19-2 decision made Tuesday by the Vaccines and Related Biological Products Advisory Committee (VRBPAC) came after hours of presentations from federal and global health officials, as well as three vaccine manufacturers. The committee’s discussion was guided by one overarching question: is now the best time to change the current COVID vaccine composition? 

The answer, naturally, was anything but straightforward. Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research (CBER) said the committee was debating “science at its hardest.” Ultimately, the advisers believed that there was no better time than the present, recommending the update for boosters. 

In parsing through available data, the committee arrived at a number of potential quagmires. The first, and arguably more important, had to do with waning vaccine effectiveness, particularly against the omicron variant, and whether or not incorporating the variant into the vaccine made a difference. Data from the CDC clearly addresses the former: after 150 days, effectiveness of three doses of an mRNA vaccine fell to 19%. 

Three of the manufacturers with recommended vaccines—Moderna, Pfizer and Novavax—then presented available research on their plans to tackle omicron. Assessed as a fourth dose, Moderna’s 50 microgram bivalent jab elicited 75% higher neutralizing antibody titers against the BA.1 omicron variant than the original formulation. Pfizer’s 30 microgram shot increased antibody titers 56% against BA.1 compared to its original shot, the BioNTech-partnered Comirnaty. 

Further complicating the data, however, is the continued spread of additional sublineages of omicron, namely BA.4 and BA.5, which have been found to further impact vaccine efficacy. During the hearing, news broke that the two subvariants made up more than half of new cases in the U.S. Only Pfizer was able to provide head-to-head data, albeit in mice, showing how its bivalent and monovalent vaccine candidates stacked up against BA.4 and BA.5. The data—which came available the morning of the meeting—showed that pseudovirus neutralization titer levels jumped 159% and 87%, respectively, compared to the original vaccine. 

Novavax, which uses a protein-based vaccine platform, surprised the committee with data indicating additional boosters of its original strain mitigated omicron’s ability to evade vaccine immunity. Committee member James Hildreth, Ph.D., M.D, said the company’s data was more compelling than either Pfizer or Moderna. 

“There are tens of millions of people who have not been vaccinated, many of whom would accept a protein vaccine, who would not otherwise accept an mRNA vaccine,” said Hildreth, who is president and CEO of Meharry Medical College. “So to me, I think it’s very compelling that we move forward on the Novavax vaccine for all those reasons.”

Novavax's shot has not yet been cleared for use in the U.S., but has been authorized in the EU. The company said data on an omicron-specific vaccine should read out in September and would be available in the fourth quarter, if the agency requests it. 

After winding through more than an hour of diverse perspectives, the committee coalesced around the benefits of updating the shot outnumbering the risks. Amanda Cohn, chief medical officer for the CDC's National Center for Immunizations and Respiratory Diseases, voted in favor of updating the shots but said the manufacturers needed to continue to compile more data. 

“[M]y belief is that this gets us the right vaccine in preparation for potential need for boosters in the fall,” she said. Cohn suggested that a bivalent vaccine, which would provide protection against two different strains, would be best. 

Pfizer promised to "continue to share our available data to health experts and regulators" so it can bring an omicron-adapted booster to market as soon as possible, according to a statement. 

The FDA will ultimately decide what vaccine will be used for the booster program, which omicron subvariant to include and whether to use any parts of the original vaccine. The agency will also decide how this recommendation impacts the vaccine used for the primary vaccination series.

Marks wouldn’t say when a regulatory decision would come down, citing the Trade Secrets Act, but said the agency would not delay a decision.

Should the FDA request bivalent vaccines that incorporate BA.4 and BA.5, the two mRNA manufacturers said doses could be available in October at the earliest.