F.D.A. Panel Weighs Challenges of Revamping Covid Vaccines for Fall

WASHINGTON – Researchers trying to design an updated coronavirus vaccine for use this fall would have to settle on a formula as early as June to meet that deadline, federal officials said Wednesday, even though some clinical trials are just beginning.

The assessment came during a daylong meeting of outside advisers to the Food and Drug Administration, who have come together to strategize about what the nation’s coronavirus vaccine policy should look like going forward. The session underscored how deeply the road ahead is fraught with uncertainties.

Among the most basic questions debated: At what point would officials decide that existing vaccines aren’t working well enough? And if better vaccines are deemed necessary, when might clinical trials provide answers about suitable replacements?

The meeting captured a transition point for the Biden administration as it tries to craft a vaccine strategy for the rest of this year. Some federal health officials are convinced that existing vaccines need to be modified to offer better protection than they do now. They hope to have a revised version by the fall, when they fear the virus could resurface in force.

Doses of the modified vaccine could cost the federal government between $5 billion and $12 billion, a senior federal official said. Congress has moved to split the administration’s new Covid budget request roughly in half, which the official said might not leave enough to cover that cost.

At the same time, vaccine manufacturers and federal researchers are scrambling to figure out what a revised vaccine should look like. A new study from the National Institutes of Health, for example, is looking at how Moderna’s vaccine works if revised to target three different variants, alone or in combination. But it just started recruiting volunteers, and results are expected sometime this summer.

Robert Johnson, director of an infectious disease division within the Department of Health and Human Services, told the panel that even once regulators decide on a reconfigured vaccine, it would take several months for manufacturers to produce doses.

“If you’re not on track for that clinical trial by early May, it’s very difficult to have enough products collectively among manufacturers to meet that demand” by the fall, he said. Dr. Peter Marks, who oversees vaccine regulation at the FDA, also described the time frame as very tight, saying regulators may need to decide on a new vaccine formula by May or June if they want to change existing ones. .

Ongoing trials are too small to provide efficacy data of the kind that led to the licensing of existing vaccines. But they could produce enough data for federal health officials to determine whether a reconfigured vaccine will create a stronger or longer-lasting immune response, a metric used to infer efficacy.

Expert after expert at the meeting described how much guesswork is involved in that effort. No one knows which variant of the virus will dominate in the fall, when federal officials consider a new surge very likely. There is a chance that before that, another variant like Omicron will emerge and redraw the face of the coronavirus in a totally unexpected way. “It’s not likely, but it’s there,” Dr. Marks said of that possibility.

Trevor Bedford, biostatistician at Fred Hutchinson Cancer Research Center, said the coronavirus had been mutating at a rate several times faster than the flu virus, for which vaccines are redesigned annually. While that pace may slow down, the virus’s plasticity indicates that “it is likely to continue to evolve,” he said.

How exactly it will do so is anyone’s guess. “There is no guarantee that every emerging variant is going to be the basis for the next variant,” said Dr. Michael Nelson, an immunologist at the University of Virginia School of Medicine.

Meanwhile, federal officials and their outside advisers continue to grapple with what the threshold is for determining that existing vaccines aren’t working well enough. Dr. Marks said the committee’s consensus seemed to be that Covid vaccines should prevent serious illness, not necessarily infections or mild illness.

The question was especially relevant because last week the FDA authorized a second booster for Americans over 50, along with a few others. But the CDC director strongly recommended those injections only for people over 65, and anyone 50 to 64 with serious underlying health conditions.

Some immunologists and vaccine experts have said the FDA lacked the data needed to authorize a second booster, while other health officials have argued that people should have the option of getting another shot.

Dr. James EK Hildreth, president of Meharry Medical College in Tennessee and a member of the committee, asked Dr. Marks why he did not seek the panel’s advice before deciding whether to authorize a second boost.

Dr. Marks said the FDA did not consider offering a second booster a “major expansion or major change.” Jerry Weir, another senior agency official, said the FDA hoped to ask the advisory panel to review any reconfiguration of existing vaccines before moving forward with emergency authorization.

Sharon Alroy-Preis, director of public health services at Israel’s Health Ministry, told the panel that administering a second booster for people over 60 earlier this year saved lives. The Israeli filing appeared to support the FDA’s decision.

But European Union regulators concluded on Wednesday that it was “too early” to give second booster shots to the general population, but that it was reasonable to offer them to people aged 80 and older.

Dr. Amanda Cohn, a senior CDC official, said data from her agency showed existing vaccines are more than 80 percent effective in preventing hospitalization in Americans without immunodeficiencies, including older people and those with chronic medical conditions. . She suggested that post-infection Covid treatments may be more effective than additional shots of vaccines in protecting Americans against serious illness.

Dr. Christopher Murray, a professor at the University of Washington whose institute has modeled trends in the pandemic, predicted that antiviral treatments like the pills recently developed by Pfizer will lower death rates even if a new variant as infectious as Omicron emerges and as deadly as Delta. .

Dr. John Beigel, director of clinical research at the NIH, described his agency’s research comparing how well Moderna’s existing vaccine works with modified versions targeting known variants, both alone and in combination.

In the first stage, the researchers hope to quickly enroll 600 volunteers who have already been vaccinated and received a booster. Some will be given the existing vaccine. Others will receive experimental vaccines targeting only the Omicron variant, as well as three other variations: Omicron plus the Beta variant, the Delta variant, and the prototype virus that emerged first in the pandemic.

In an interview Tuesday, Dr. Beigel said existing vaccines may still prove to be the best. He said he expected the results of his trial to be ready by mid-summer, although some federal officials hope it will be sooner.

Deciding on the next step, he told the panel, “is going to be a challenge.”

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