The U.S. Food and Drug Administration wants COVID-19 manufacturers to target the latest BA.4/BA.5 coronavirus strain in their boosters for the fall, the agency said Thursday.
The swift decision from the agency, following an advisory panel earlier this week, could give manufacturers a chance to meet the October booster campaign deadline the FDA is targeting. But they will now have to pivot from their focus on the original Omicron (BA.1) strain.
It's why the FDA requested clinical trials begin for the latest strain, but it is unclear if the data will be available to evaluate the booster doses before authorization for use in the fall.
"Vaccine manufacturers have already reported data from clinical trials with modified vaccines containing an Omicron BA.1 component and we have advised them that they should submit these data to the FDA for our evaluation prior to any potential authorization of a modified vaccine containing an omicron BA.4/5 component," the FDA's Dr. Peter Marks said in a statement.
"Manufacturers will also be asked to begin clinical trials with modified vaccines containing an omicron BA.4/5 component, as these data will be of use as the pandemic further evolves," he added.
A panel of outside advisers to the FDA voted overwhelmingly to include Omicron-targeting components in boosters expected for the fall on Tuesday.
The vote, 19 yes and 2 no, did not specify if the boosters should be an Omicron-only vaccine or a bivalent shot — one that includes the original strain of the coronavirus. The vote also did not clarify if the target should be the original Omicron (BA.1) or the new subvariants (BA.4, BA.5) that comprise a majority of cases in the U.S. today.
Kanta Subbarao, chair of the World Health Organization's Technical Advisory Group on COVID-19 Vaccine Composition, told the FDA panel that an Omicron-targeting booster would be necessary, but is not ideal as a primary dose — which makes the original vaccines still relevant for those yet unvaccinated.
The vaccine companies presenting that day had different data and vaccine options, but most relied on lab analyses or were still working on collecting data as of the meeting date. They also did not have head-to-head comparisons of BA.1 to BA.4/BA.5.
This concerned some of the experts, who expressed as much at the meeting Tuesday.
Dr. Paul Offit, a voting member and director of the Vaccine Education Center at the Children's Hospital of Philadelphia (CHOP), told Yahoo Finance his concerns from Tuesday have not been addressed by the FDA announcement Thursday.
He had previously asked Moderna's (MRNA) president Stephen Hoge if the company had yet done a comparison of the BA.4/BA.5 bivalent vaccine candidate against the original coronavirus, known as ancestral, strain.
"We are still collecting that data," Hoge said on Tuesday.
That puts a point on the concern that other experts expressed — that the decision was made prior to having any actual data.
"This is a new product, and I think as a new product it should be handled as a new product...we need a higher standard for protection than what we're being given, I think it's uncomfortably scant," Offit said Tuesday.
In addition, the question of whether or not a booster was needed at all was raised. Dr. Cody Meissner, a voting member and chief of the division of pediatric infectious disease at Tufts Children's Hospital, noted that while Omicron variants are more transmissible than previous strains, they haven't been as deadly — and the vaccines will not protect as well against infection as they did before.
Which begs the question of does targeting BA.4/BA.5 make sense in light of the speed at which variants have emerged in the past two years — and what could be relevant by October.
"The question is will the strain mutate so that it's resistant to the immunity that's generated by the vaccine. It's very hard to tell when that will happen," Meissner said.
He and others also noted that its possible to reach a point when boosting may not be needed at all, and longer-term memory cell protection in our bodies could play a role.
Dr. Céline Gounder, editor-at-large for public health at Kaiser Health News and an infectious disease specialist, told Yahoo Finance that the current analyses and modeling for the subvariants does not provide any real understanding of what type of protection the vaccines offer.
"We need to better model what fold increase is truly significant," she said. "Once you hit four-to-five fold, that's a more significant increase, and may justify an update in the vaccine. But if it's only a two-fold increase, in the antibody levels, that really doesn't justify (boosters)."
Gounder noted that the debate and uncertainty about the strategy was rooted largely in lack of clinical data.
The timeline pressure
Marks, director of the FDA's Center for Biologics Evaluation and Research, said during the panel Tuesday that the manufacturers needed direction as early as possible in order to meet the fall booster timeline.
"For the mRNA vaccines, its probably about a three-month window form when they have some idea of what they are going to manufacture to when they can start to have product. That may not be that they will have the full amount of product for the booster campaign, but they will start to have that product," Marks said.
The companies indicated that they could have more product sooner of the BA.1 vaccine as they have already begun to produce, at-risk. But if they were directed to pivot, it would push out the timeline.
Moderna, for example, would be ready by August for a BA.1 rollout, but would need to push to late October, early November for a BA.4/BA.5 bivalent vaccine. Pfizer (PFE)/BioNTech (BNTX) said it would be ready by early October. Novavax (NVAX) said it would target the fourth quarter, broadly, indicating anywhere between October and December — even as its original vaccine has not yet been authorized for use in adults.
But Moderna's Hoge noted that the timeline was based entirely on manufacturing needs alone — which could be disrupted in light of the clinical trial request.
"Again assuming no clinical data requirements, no data to assess the vaccine at all....and assuming a rapid review cycle," Hoge said of having a significant amount of the new vaccine produced.
Eligibility and funding
Even with the debate over what the right strategy should be, the question of who will be eligible for the additional doses is also still on the table. In part due to a battle for funding from Congress, and in part the debate over the benefit of the vaccines.
To that end, the U.S. government committed to purchasing 105 million additional doses — for all ages, which includes 30 microgram, 10 microgram and 3 microgram doses — for the Fall. The government has an option to purchase up to 195 million more doses. The cost is $3.2 billion. In total, to-date, the government has purchased nearly $15 billion worth of doses from Pfizer/BioNTech — or nearly half of the projected vaccine sales of the company
Meanwhile, the U.S. has set aside $5 billion for boosters, taking away from treatment and protective equipment funding, as a $10 billion funding request to Congress has stalled.
That amount of funding available would dictate who could be covered for boosters in the fall.
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