FDA Panel Backs Plan to Only Use Omicron-Containing COVID Vaccines

The FDA's vaccine advisors unanimously backed the agency's proposal to harmonize COVID-19 primary and booster vaccines to contain a single bivalent composition with components targeting BA.4/5 and the original SARS-CoV-2 strain.

With a 21-0 vote on Thursday, members of the Vaccines and Related Biological Products Advisory Committee (VRBPAC) supported FDA's plan, which aims to offer better protection to the currently circulating variants and to reduce administration confusion.

In practice, eliminating the monovalent vaccine for primary series vaccinations may have a minimal impact. According to CDC's vaccine tracker, 81% of the U.S. population has received at least one dose and 69% have completed their primary series, and these numbers generally haven't moved much over the past year. (Monovalent vaccines had already lost authorization as boosters following the bivalent vaccine rollout last year.)

Advisors also weighed in on the agency's plan for annual COVID boosters similar to the flu shot, with strain selection in May or June of each year to meet a September rollout, and streamlined dosing recommendations, though no votes were tied to these discussions.

While presenters from Moderna and Pfizer said this timing would be feasible, given the quicker turnaround with the mRNA platform, a representative from Novavax said it could take 6 months to manufacture their vaccine from scratch.

Committee members questioned if future vaccines might include multiple COVID-19 strains.

"Do we need to continue to have ancestral strain in the vaccines?" asked Paul Offit, MD, of the Children's Hospital of Philadelphia.

On dosing, FDA is proposing to offer a single updated booster for most of the general population and two doses for young children who have not yet been vaccinated, older individuals, and for individuals with immunocompromising conditions.

Peter Marks, MD, PhD, the agency's top vaccine official, explained during the meeting that dosing for the immunocompromised in particular warrants further study.

"The modest immunocompromise of a diabetic compared to the tremendous immunocompromise of someone who has received CD20-depleting therapies is a real spectrum here that we're dealing with," said Marks.

Committee members did not oppose the plan, but overwhelmingly expressed the need for more data for the coming formulation decisions. Several committee members asked the FDA for more precise endpoints, whether they should be aiming for lower infection, hospitalization, or deaths?

"This virus is going to be with us for years, if not decades," Offit said during a roundup discussion.

"The CDC needs to tell us exactly who it is getting hospitalized and dying from this virus," he said, including information on age, comorbidities, type of immunocompromising condition, vaccination status, and whether they received antivirals.

"That has to be provided in concert with immunological data, presumably from academic immunologists, as to what exactly were the immunological predictors -- not just antibodies, but also cellular immunity," said Offit. "Only then can we best make the decision about who gets vaccinated, and with what and when."

Panelists also heard findings that recently triggered a safety review on Pfizer's bivalent vaccine. As was previously reported, subsequent reviews of multiple other databases turned up no similar link with Pfizer's or Moderna's bivalent vaccines, but the CDC said it would continue to review the data.

The signal came from CDC's Vaccine Safety Datalink, which detected a higher risk of ischemic stroke in the first 21 days following receipt of Pfizer's bivalent booster when combined with high-dose or adjuvanted flu vaccine compared with the 22-42 following vaccination (40 vs 20 cases; RR 2.00, 95% CI 1.18-3.48).

But Nicola Klein, MD, PhD, of Kaiser Permanente in Oakland, California, who presented the findings, noted that 34.5 cases would have been expected during a 3-week interval.

"Is this a higher rate within the risk interval or is it an unexpected lower rate within the comparison interval? I think it's a bit of both," said Klein.

Harmonizing the Vaccine Strain

Presentations from the FDA, CDC, Moderna, Pfizer, and Novavax, along with data from independent researchers backed the move, with study after study supporting effectiveness of the bivalent shots, whether it be better neutralizing antibody activity, reduced symptomatic infection, or reductions in hospitalizations in older adults.

"I am totally convinced that the bivalent is beneficial as a primary series and as boosters. Furthermore, the updated vaccine safety data are really encouraging so far," said David Kim, MD, MS, MHA, of the Department of Health and Human Services, following the vote.

He added that if clinicians and pharmacists have been needing diagrams and posters just to sort out who needs which vaccine and when, then that's another reason for a simpler formulation. "I enthusiastically support this recommendation," he said.

Hayley Gans, MD, of Stanford University Medical Center in California, added that she wholeheartedly agrees this could help increase vaccine uptake. However, she said, "this isn't only a convenience thing to increase the number of people who are vaccinated ... the science also supports this move."

But while the bivalent vaccines' effectiveness was not disputed, there was little data presented on using the bivalent as a primary series, though early trials in toddlers presented by Moderna suggested better immunogenicity with the bivalent shot.

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