In historic vote, mRNA vaccines go 2 and 0 as FDA experts unanimously back Moderna's Covid-19 vaccine
Come Saturday, the US will likely have two Covid-19 vaccines.
The FDA’s advisory committee on vaccines voted unanimously Thursday — with one abstention — to recommend an emergency use authorization for Moderna’s mRNA-based Covid-19 shot, setting the agency up to likely issue the EUA on Friday. The agency does not have to listen to the committee but usually does.
“The evidence that has been studied in great detail on this vaccine highly outweighs any issues that we’ve seen,” Stanford infectious disease pediatrician Hayley Gans said. “And I think really supports us being able, with the pandemic, move forward and finally provide a safe and effective way of getting to herd immunity.”
The unanimous vote contrasted with last week’s advisory hearing on Pfizer-BioNTech’s own mRNA shot, where four committee members voted against the question put to them and one abstained. But the discrepancy may come down to a minor difference between the two applications.
Pfizer asked for an EUA to vaccinate anyone 16 years of age or older, but some members of the committee were concerned that Pfizer did not conduct sufficient testing on 16 and 17 year olds and voted accordingly, even though they supported vaccinating anyone over 18. Moderna only requested an EUA for people 18 and up, assuaging the committee’s concerns.
Nevertheless, some advisory members still sparred with the FDA over the wording of the question put before the committee, fearing that the wording may mislead the public into believing that the vaccine has been fully approved. They offered adding “experimental” or “emergency use authorization” to the question.
“This can be interpreted as recommending full approval,” said NCAT’s Michael Kurilla. “That may… preclude not only adequate evaluation of this vaccine but also future and ongoing Covid vaccines in development.
FDA officials and other members, however, quickly shot down the idea.
“The question is never when do you know everything, it’s when do you know enough,” said Paul Offit, an infectious disease physician at Children’s Hospital of Philadelphia.
Kurilla abstained over the wording, as well as concerns that an expanded access protocol may have been more appropriate than an EUA, allowing trials to continue to collect randomized data.
An EUA for Moderna would roughly double the amount of vaccine immediately available in the U.S., from over 20 million doses to over 40 million doses. The vaccine is also easier to distribute as it can be handled at the same temperature as most approved vaccines — unlike Pfizer’s shot — and the U.S. has exercised options to acquire 200 million doses through June.
While proffering dozens of questions, the committee never expressed serious concerns about the safety or effectiveness of the vaccine. Moderna announced previously that the vaccine was 94.1% effective at preventing symptomatic Covid-19. Although the FDA review revealed that the vaccine appeared less effective in volunteers over 65 — 86.5% protection — company executives noted that the difference was not statistically significant.
Instead, discussion centered on rare potential side effects and Moderna’s plan for what to do with adverse events. The FDA’s review turned up one surprising serious event: Two volunteers who had previously received a dermal filling experienced facial swelling after receiving the vaccine.
The panel asked repeatedly the allergic reactions that have emerged in the two weeks since Pfizer’s vaccine was inoculated. Although Moderna said they did not see any cases of anaphylaxis in their study — outside of one allergic reaction two months out, from someone with a soy allergy — they also noted it as one potential serious event to monitor long term.
Still, Moderna CMO Tal Zaks cautioned that each component of the company’s lipid nanoparticle, which may have triggered the allergic reaction in Pfizer recipients, was different chemically than the Pfizer-BioNTech vaccine.
“While we all might say, oh there’s an LNP here, there’s a lipid and mRNA, therefore they must be all be the same,” he said. “I would not necessarily assume that.”
The only point of continual friction between Moderna and the panel arose around the question of what the company should do with their Phase III trial after an EUA is issued. The group was skeptical last week when Pfizer proposed gradually unblinding participants as they become eligible for vaccine under CDC priority guidelines. Moderna wanted to go further, immediately offering the vaccine to all placebo participants, regardless of whether they would be eligible.
Moderna executives said that they needed to unblind to prevent volunteers from dropping out of the study, and because placebo participants are and would continue to be infected. They said they could vaccinate them with clinical supply of the vaccine that would not draw from their commercial stable.
“Additional severe cases and death are a question more of when than a question of if,” Moderna senior vice president Jacqueline Miller said.
Many advisors rejected the approach, proposing that Moderna either follow Pfizer’s plan or adopt an approach where the trial would stay blinded but participants in the vaccine arm would get placebo and volunteers in the placebo arm would receive vaccine, allowing comparisons on durability and long-term adverse events. A few, however, backed the Moderna approach, saying the blinding proposal and even the Pfizer approach may be infeasible.
The debate got to the point that at least two different advisors proposed the agency allow the panelists to vote on the issue, although they had not originally been asked to do so.
“It seems to me that there’s an assumption that Moderna is going to do what it’s going to do. It doesn’t have to be that way,” Sheldon Taubman, the consumer advocate on the panel, said. “We weren’t asked to vote on it, but we could vote on it.”
Marion Gruber, director of the offices of vaccine research at the FDA, though, neutralized that idea, citing the “complexity of the situation” and the fact that they did not ask the committee to vote on the same issue at the Pfizer trial. The hearing ended without a resolution.
“I think we gave FDA a sense of our with that we could do a crossover blinded design, but the realization that that may be impossible,” committee chair Arnold Monto said. “FDA will be negotiating with Moderna about the way they will address this problem.”
