51成人动漫

An FDA advisory committee voted unanimously (with one abstention) Thursday to recommend the Moderna COVID-19 vaccine (mRNA-1273) for use in adults.

Based on the totality of scientific evidence available, the FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted 20-0-1 that benefits of the vaccine "outweigh its risks for use in individuals 18 years of age and older," so the vaccine would qualify for FDA emergency use authorization (EUA).

Most of the discussion centered around how the voting question would be interpreted, with some participants concerned that its broad wording would be construed as an "approval."

Michael Kurilla, MD, PhD, of the NIH, abstained, saying he was "very uncomfortable with the language"; he preferred a more targeted recommendation of the vaccine to those at high risk.

A. Oveta Fuller, PhD, of the University of Michigan, voted yes. While she said an EUA was not her preferred pathway, "the train had left the station" and said she supported the authorization.

Acting VRBPAC chair Arnold Monto, MD, also of the University of Michigan, observed that while the vote was "even more overwhelming than last week" for the Pfizer/BioNTech vaccine, it should not be interpreted as one vaccine being better than the other. (That product received four "no" votes, with members explaining they disagreed with the inclusion of people age 16 and 17.)

Potential unblinding and crossover of placebo recipients continued to be a major issue, especially as the Pfizer/BioNTech vaccine is now available under an EUA for healthcare professionals. Indeed, Lindsay Baden, MD, of Brigham and Women's Hospital in Boston, and principal co-investigator on Moderna's , noted vaccine participants are "voting with their feet" and researchers experienced "substantial dropout" in the trial since participants can now potentially receive the product.

Baden discussed an open-label crossover trial design, where placebo recipients could get the vaccine. Moderna has residual vaccine doses that expire shortly and would not be suitable for distribution under the EUA, which could be used for this purpose.

"I don't think it's an issue of a double-blind study or nothing," he said, saying vaccine trials need to "face reality" about the feasibility of continuing double-blind trials during a pandemic.

Members understood the reason for the open-label design, recognizing that converting to a double-blind crossover design, which would require changing the protocol, was not feasible. They wanted to see continued immunologic studies and those addressing asymptomatic infection, regardless of trial design. Researchers also expressed hope the continuing Moderna COVID-19 vaccine trial could offer insights into immune correlates of protection.

Several members asked whether they could vote to recommend how Moderna proceeded with its unblinding, but FDA staff shut down that idea, saying they only wanted discussion and not a vote. Monto clarified that FDA would be "negotiating with Moderna" about how to address this problem.

Reported severe allergic reactions, including anaphylaxis, also weighed heavily on the minds of both FDA and Moderna staff. Doran Fink, MD, PhD, of FDA's Office of Vaccines Research and Review, noted reported by vaccinated U.S. healthcare workers receiving the Pfizer vaccine, including one case of anaphylaxis who required hospitalization.

"We anticipate that there will be additional reports, which we will rapidly investigate" with CDC, he said. He noted FDA is also working with Pfizer to further revise the vaccine's fact sheet with information about severe allergic reaction and would do the same with Moderna's.

In its presentation, Moderna said no cases of anaphylaxis had arisen within 48 hours of dosing, though two showed up later: one in the placebo group 10 days after the first dose, and one in the vaccine group 63 days after the second dose. The company plans an active surveillance program using a database of 45 million adults from a linked healthcare claims data source, to identify expected rates of cases.

This seemed to satisfy the committee. Moderna reported its final efficacy data (the same as presented in briefing documents): 94.1% overall efficacy (95% CI 89.3%-96.8%), with 185 COVID illnesses in the placebo group versus 11 in the vaccine group.

Moreover, the vaccine was 100% effective against severe COVID-19, with 30 cases in the placebo group (nine resulted in hospitalization and one resulted in death) and zero in those vaccinated. Data supporting the EUA application were primarily from study P301 -- dubbed COVE by Moderna -- a phase III, randomized, placebo-controlled trial co-sponsored by the National Institute of Allergy and Infectious Diseases.

Examining safety, nearly all participants experienced injection site pain, with about two-thirds reporting fatigue and headache, and almost 60% reporting muscle pain. Mild to moderate reactogenicity was more common in adults younger than age 65.

Given the lopsided vote, an EUA for the product appears certain. When asked by committee members how to counter the idea that emergency use authorization is not approval, Monto responded, "Whatever we say, the media is going to interpret it in whatever way they want."

The FDA does not have to follow the advice of its advisory committees, but it often does.

Comment