麻豆传媒

An FDA advisory panel recommended emergency use authorization (EUA) of a booster dose of Moderna's COVID-19 vaccine for adults ages 65 and older, as well as for younger adults with high-risk medical conditions or at high risk of occupational or institutional exposure.

On Thursday, the FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted 19-0 that the known and potential benefits of a booster dose outweighed the known and potential risks in these populations.

And while VRBPAC did not vote on the issue, they remained against the idea of mRNA vaccine boosters for all adults, given the lack of a benefit-risk assessment, and questioned why everyone ages 18 and up would require a booster when the primary series still generally protects against severe disease.

Most committee members were supportive of the idea of a Moderna booster dose in select populations, though several questioned how thin the sponsor's submission package was.

Moderna presented data from a phase II trial, , where participants were randomized to receive either a two-dose 50 μg series, 100 μg series, or placebo (part A), and then a 50 μg booster dose (part B).

Overall, 149 adults who received the two-dose 100 μg series (the dose authorized under EUA) plus the booster dose were evaluated for immunogenicity.

While "immunobridging analyses against the D614G strain met the pre-specified success criteria for the [geometric mean titers] ratio," FDA staff added that with regard to seroresponse rates after the booster dose, "the pre-specified success criterion was not."

Despite voting yes, Patrick Moore, MD, of the University of Pittsburgh Cancer Institute, called out the poor quality data submitted by the sponsor, saying that it required an explanation from the FDA.

"I've got real issues with this vote ... [it's] more of a gut feeling rather than really truly serious data," he said. "I think it's very important that companies coming to VRBPAC ... really take seriously that we need to see good, solid data, and it needs to be explained well."

Moore added that while the data were not strong, "it is certainly going in a direction that is supportive of this vote."

Indeed, committee members were more impressed with the real-world Israeli data on Pfizer boosters, which found that not only did a booster dose show improved protection against infection in individuals ages 16 and up, and improved protection against severe disease in adults ages 40 and up, it came with minimal adverse events.

"I find the Israeli data compelling," said Mark Sawyer, MD, of the University of California San Diego. "Although the amount of safety data presented by the company was very minimal, I take some reassurance from the 1.5 million citizens who received the vaccine."

The safety population in Moderna's P201 trial was 344 participants, but only 171 received the primary series, which raised some eyebrows among VRBPAC members. However, Israeli data on Pfizer's vaccine found that the risk of myocarditis was no higher following the third dose than the second dose.

And when questioned by committee members about the low sample size for safety, FDA staff confirmed that was adequate for an EUA.

"One would need a significantly larger database by orders of magnitude, and that is for post-authorization to address," said Doran Fink, MD, PhD, of the FDA.

Peter Marks, MD, PhD, director of the FDA's Center for Biologics Evaluation and Research, also noted that the agency will continue to study myocarditis, "looking at our large database" and make sure incidence is not "excessive" once the vaccine is deployed.

Some questions arose about the third population being voted on -- those adults ages 18-64 with high risk of occupational or institutional exposure -- specifically, the idea that they are at increased risk of severe disease is not "evidence-based."

However, James Hildreth, MD, of Meharry Medical College in Nashville, commented that frontline jobs, such as grocery store clerks, are "Black and brown people who are more likely to have underlying conditions to put them at severe risk," he said.

Other committee members agreed that those groups should be included in the vote, and FDA staff urged the committee to be as specific as possible with their recommendations "to allow flexibility in making the vaccine available under EUA to individuals for whom it can provide benefit," Fink said.

The FDA also asked VRBPAC to discuss the need for mRNA boosters for all adults, but committee members noted that most younger adults are well-protected by the current vaccines against severe disease.

"I am not convinced the epidemiology of the pandemic at the moment supports this request," said Archana Chatterjee, MD, PhD, of Rosalind Franklin University in North Chicago. "We are seeing cases go down without booster doses."

She added that if you add the sample sizes of the populations in the Pfizer and Moderna trials to support an EUA for boosters, they don't even reach 500 people, and this decision "could impact tens of millions of people."

Paul Offit, MD, of the Children's Hospital of Philadelphia, also thought it might add to the confusion about the purpose of the vaccine.

"We haven't clearly defined what the goal of this vaccine is" and if it's to stop "erosion of protection against mild and asymptomatic infection ... that is a high bar to which we hold no other vaccine," he said.

Committee members called for a benefit-risk assessment, to see which populations younger than age 65 would benefit from a booster dose. For example, in some communities of color, starting boosters closer to age 50 might make more sense, they added.

Marks said the agency would go back and try to come up with decisions that make the most sense.

"I think we heard loud and clearly that there is not a lot of appetite for moving significantly down the age range, if it all," he said.

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