As expected, the FDA's Vaccines and Related Biological Products Advisory Committee voted near-unanimously on Dec. 17, with one abstention, that available evidence shows the benefits of Moderna Inc.'s COVID-19 vaccine, mRNA-1273, outweigh its risks for people 18 and older. The vote bolsters the likelihood that the regulator will grant the vaccine an emergency use authorization (EUA), which could come as soon as Friday.
Not the same as an approval, the authorization would allow for the vaccine's use for the prevention of COVID-19 in the U.S. even as further trials and regulatory evaluation remains underway ahead of a company BLA submission. If granted, the EUA would make Moderna's COVID-19 vaccine the second to receive an EUA following the regulator's grant of one to Pfizer Inc. and Biontech SE on Dec. 11.
Shares of Moderna (NASDAQ:MRNA) climbed 5.1% to $144, though pulled back somewhat in after-hours trading.
Despite some short-lived argument over the language of the sole voting question before the committee, its 21 voting participants expressed clarity about the urgency of adding a second vaccine to the U.S.'s emergency arsenal amid the ongoing pandemic, which as of Thursday had killed nearly 310,000 people in the U.S., sickening millions more.
"This is a really opportune time for us to move science forward and I would say that the evidence that has been studied in great detail on this vaccine highly outweighs any of the issues that we've seen," said committee member Haley Gans, a professor of pediatrics at Stanford University Medical Center. "I think it really supports us being able to, with the pandemic in our background, really move forward and finally provide a safe way to get to herd immunity," she said. While acknowledging that there's still a need to get the vaccine to people younger than 18, she said an EUA would still offer a first step.
Paul Offit, a professor of pediatrics at The Children's Hospital of Philadelphia, saw similar obviousness in the question before the committee. Even though he expressed concern about three cases of Bell's palsy seen in the vaccine treatment group vs. one in the placebo group for Moderna's phase III trial – cases for which the FDA said it has "no clear basis upon which to conclude a causal relationship at this time" – he said that any severe safety issues were, for now, "theoretical risks."
"The question is never when do you know everything? It's when do you know enough?" Offit said. With just nine weeks of follow-up data provided to the FDA and the committee as a basis on which to make their decision, he said that "we don't know whether [the vaccine] is going to be effective six months from now or a year from now. But there are systems available to know that. We don't whether or not it's going to have a rare serious side effect. But there are systems in place to know that," he said.
Despite the overwhelming support, there was still one abstention from the vote. That was cast by Michael Kurilla, director of the division of clinical innovation in the NIH's National Center for Advancing Translational Sciences. In explaining his decision, he suggested that the age range included in the voting question was too broad in light of limited vaccine supply available. "I'm not convinced that for all of those age groups the benefits do outweigh the risks and I would prefer to see it more targeted towards people at high risk of serious and life-threatening COVID disease." Furthermore, he said he would have preferred an expanded access path to availability instead of the EUA.
FDA's positive framing
As the day-long meeting kicked off, Doran Fink, deputy director for the agency's division of vaccines and related products, said his team felt "confident that we have enough information to justify issuing an EUA for this vaccine, should everyone agree that the benefits outweigh the risks based on the clinical data."
Following two reports of anaphylaxis and one report of a possible allergic reaction to the first vaccine to receive an EUA, Pfizer and Biontech's BNT-162b2, Fink addressed additional reports that two workers at an Alaska hospital suffered allergic reaction to the vaccine. He said the agency was working with Pfizer to revise labeling for the product, but meanwhile anticipated that there would be more reports of such reactions, underscoring the need to remain vigilant during the early phase of the vaccination campaign.
Keenly aware of the interest in the issue and its import as wider distribution of COVID-19 vaccines get underway, Moderna's team also addressed the issue. During the course of the Cambridge, Mass.-based company's ongoing phase III study of mRNA-1723, its team has "actively scrutinized" its safety data to identify and analyze possible cases of anaphylaxis, said David Martin, the firm's vice president of pharmacovigilance. So far, it has found no cases suggestive of anaphylaxis to the vaccine candidate, though two anaphylactic reactions have been reported to the company as adverse events, Martin said.
One case occurred in the placebo arm of the trial, called Study 301, and the other occurred in the mRNA-1273 arm. The placebo arm event occurred 10 days after the first dose, and was attributed to co-administration of radiocontrast dye, he said. The mRNA-1273 event occurred 63 days after the second dose of the vaccine in a person with a history of asthma and allergy to shellfish.
Public comment during the meeting touched on a range of topics, but gravitated most heavily to issues surrounding vaccine deployment and acceptance in communities of color, where trust in government and pharmaceutical companies has been eroding for decades. Commenters also touched on special concerns around the lack of data generated about vaccine safety and efficacy in pregnant women, incarcerated individuals and the corrections system employees who work with them.
"While it's highly unlikely that we will make our institutions more trustworthy over the course of the next few weeks, as vaccines are rolled out," said Bisola Ojikutu, an assistant professor of medicine, global health and social medicine at Harvard Medical School, "I and others believe that the same amount of effort and funding that was placed into the development of this and other successful vaccine candidates needs to be directed to ensuring uptake and promoting vaccine confidence, specifically within Black, Latinx and indigenous communities that are most affected."
Adcom members also spent a significant portion of time engaged with how Moderna should proceed with the trial in light of a potential EUA issuance for its candidate and growing availability of the Pfizer/Biontech vaccine. Though the conversation was complex and, at times, appeared frustrated by the intrusion of messy realities on the pursuit of strong scientific answers in placebo-controlled trials, some semblance of concordance eventually emerged. It seemed to converge on a grudging support for Moderna's plans to unblind its phase III study participants and offer those who received placebo the vaccines, similar to a plan being pursued by Pfizer and Biontech.
Following the vote, Moderna CEO Stéphane Bancel said that his team has been working with the CDC to prepare for distribution of mRNA-1273 if the FDA chooses to grant the EUA.