With Pfizer EUA For 5-11 And Moderna Delay For Adolescents, US FDA Walks Myocarditis Tightrope
Executive Summary
COVID vaccine safety concerns from international analyses will force sponsors and FDA to again confront the challenge of how to make bad news for one shot not turn into bad news for all.
The US Food and Drug Administration offered treats and probably a little bit of a scare to COVID vaccine sponsors on the Friday before Halloween when it gave Pfizer Inc. emergency use authorization for its COVID-19 vaccine in children 5-11 and then apparently told Moderna, Inc. that safety concerns would extend the review of its vaccine for use in 12- to 17-year-olds.
Moderna announced on 31 October that “on Friday evening, the FDA informed Moderna that the agency requires additional time to evaluate recent international analyses of the risk of myocarditis after vaccination” and that the review “may not be completed” before January 2022.
“To date, the observed rate of myocarditis reports in those less than 18 years of age in Moderna’s global safety database does not suggest an increased risk of myocarditis in this population,” the company said. “Moderna is committed to conducting its own careful review of new external analyses as they become available,” though it noted that it does not yet have access to data from some recent international analyses.
“Moderna will delay filing a request for EUA of mRNA-1273 at the 50 µg dose level in the pediatric population (6-11 years of age) while the FDA completes its review of the adolescent EUA request,” the company said.
Coming the same weekend as Pfizer saw its EUA for the 5-11 population cleared by FDA, Moderna’s announcement of the review and filing delays is a reminder that although the firms announced the start of pivotal trials for their vaccines on the same day last year, Pfizer has moved far faster since then. The big pharma got initial authorization first, then an EUA in adolescents, full BLA approval, and now a pediatric EUA, all while Moderna continues to struggle with step two.
That widening gap is undoubtedly due a bit to chance, but is probably mostly a function of the fact that Pfizer is a biopharma behemoth with a sizable vaccine portfolio, while Moderna remains a startup that still technically doesn’t have an approved product yet.
Another factor might be just what could be called dumb luck. The companies settled on different doses for their initial regimens – 100 mcg for Moderna compared to just 30 mcg for Pfizer – and while that didn’t seem to make much of a difference in the initial trials, subsequent studies have suggested that Moderna’s vaccine could offer stronger real-world protection, making the choice to offer bigger doses with a bigger gap between them seem like a good bet.
But fast forward a bit longer and the emergence of the myocarditis side effect now makes those bigger doses in smaller recipients seem potentially more worrisome. And while the vaccines are of course not directly comparable, it’s worth noting that the pediatric formulation that Moderna developed is a higher dose than the adult version of Pfizer’s shot.
None of this means that the Moderna vaccine won’t be authorized in adolescents or that Moderna might have to go back to the dosage drawing board. But it does underscore the pressures the sponsors and FDA are under regarding vaccines, especially ones that will be administered to kids.
Pfizer, Moderna and FDA all want to bring out vaccines that will have a meaningful impact on the pandemic but not endanger the recipients, and unfortunately there’s not something that’s absolutely effective and absolutely risk free.
So FDA hopes that its models showing that vaccinating the pediatric population is worth it even with low incidences of COVID will help convince people to get the shot, while also hoping that putting an application for another vaccine on ice won’t convince them otherwise.
It’s not unlike the balancing act that government officials trials tried when they recommended a pause to administration of the J&J shot earlier this year. The product never really recovered and vaccinations overall declined as well, though some have argued that the pause basically coincided with the predicted crest of demand, so the drop-off in shots wasn’t a function of the safety scare.
A smaller portion of younger kids will get the Pfizer shot than adolescents did, and fewer of them have gotten it than adults. That was true even before the Moderna news and stems from the perception that kids are less at risk of COVID, and that there are no mandates in the younger population.
Those mandates may be coming, though; California has moved to require vaccination for school children once a BLA is approved in their ages. At a 29 October press conference apparently held before the agency communicated with Moderna, FDA acting commissioner Janet Woodcock said she couldn’t comment on when full approvals might be forthcoming.
“There are so many factors that are unknown in this pandemic, including where we have additional variants arise,” Woodcock said. “We will be obviously be monitoring all the effects … so we can’t give specific timeframes for approvals.”
CBER director Peter Mark was slightly more specific when discussing potential authorization for children under five. “We’re probably a few more months off from the younger children. It has to do with when they were enrolled in the trials and the fact that as we get down to younger children, the benefit/risk gets to be even more of a careful consideration because the youngest children are affected the least directly in terms of severe COVID-19.”