FDA Advisors Uncertain on EUA Pathway for Younger Kids’ COVID Shots

An FDA vaccine advisory committee was torn on whether emergency use authorization (EUA) was the right step for COVID-19 vaccines in younger children, but there was broad agreement that key safety concerns will have to be worked out on the market.

The Vaccines and Related Biological Products Advisory Committee met Thursday via videoconferencing to discuss, but not vote, on the evidence that would be required for the population ages 6 months to 17 years.

“We’re hearing we need the vaccines soon in children, because we do not know what the virus will be doing in the fall when kids are back in schools and people are indoors,” summarized Marion Gruber, PhD, director of the FDA Office of Vaccines Research and Review, toward the end of the full-day session. “We are in the very difficult position at FDA to really weigh that availability with the desire to do clinical trials in thousands of pediatrics subjects.”

Pfizer already obtained an EUA down to age 12 years for its vaccine, and Moderna filed Thursday for EUA in those ages 12 to 17 as well, citing positive TeenCOVE trial data.

Children 12 and up are much more like their older counterparts in immunogenicity. But the considerations are “more complex” for younger children, noted Doran Fink, MD, PhD, deputy director of the clinical side of the FDA’s Division of Vaccines and Related Products Applications, in presenting to the panel.

He presented a plan to allow manufacturers to continue using so-called immunobridging trials, which just have to prove that the vaccines are at least as good at generating immunity markers as they are in younger adults without formal hypothesis testing of clinical disease prevention.

For licensure, at least 1,000 vaccine recipients in each younger age group (6 months to 1 year, 2 to 5 years, and 6 to 11 years) would need to be studied in a safety database with median 6 month follow-up. For EUA, it would just depend on how the epidemiology curves are looking, potential benefit, and potential risk, said Fink.

“A conclusion of clear and compelling safety and effectiveness to support emergency use authorization and, indeed, the need for emergency use authorization may be less certain for younger pediatric age groups than for adolescents and adults,” he said.

How Much Benefit

Children are susceptible to the SARS-CoV-2 virus and can transmit it, although they less often seek testing or develop severe disease compared with adults, noted Hannah Kirking, MD, an epidemiologist with the FDA’s Respiratory Viruses Branch and a lieutenant commander in the U.S. Public Health Service.

She pointed to new CDC data showing teens’ hospitalization rates spiked early this year, with a peak of 2.1 per 100,000 in youths ages 12 to 17, and that one-third of those hospitalized needed ICU care.

And the multisystem inflammatory syndrome in children (MIS-C) has consistently trailed behind the adult epidemiologic curves, tallying up some 4,000 cases over the last year, she noted.

However, the epidemiologic curve has shifted downward dramatically in the last month or so, argued panelist H. Cody Meissner, MD, director of pediatric infectious diseases at Tufts Medical Center in Boston. “I very strongly believe we need a vaccine for adolescents and children. But I want to be sure that the risk of the vaccine is less than the risk of hospitalization, because four per million certainly does not constitute an emergency.”

He argued for a full biologics license application instead of EUA for children.

What the virus will do in the future, though, “is the million dollar question,” responded Kirking. With more transmissible variants and many children headed back to in-person schooling in the fall, there’s no guarantee that case counts will remain as low as they are now, she cautioned.

The risks to children from COVID-19 are far larger than many of the other viral diseases for which Americans routinely vaccinate children, added panelist Eric Rubin, MD, PhD, of Harvard School of Public Health in Boston and editor-in-chief of the New England Journal of Medicine.

“We still vaccinate children in this country for polio every year, even though we haven’t had a case of polio since the 1970s,” agreed Paul Offit, MD, an infectious diseases specialist at the Children’s Hospital of Philadelphia.

With much of the globe still unvaccinated, “we’re going to have to have a highly vaccinated or highly immune population for years, if not decades,” he said. “It just seems silly to think we don’t have to have children as part of that since they can suffer and be hospitalized and occasionally die from this virus.”

It’s better to have a tool in the arsenal that doesn’t end up being needed than not to have it if it is needed sooner than the licensure process would allow, Rubin argued.

How Much Safety Risk

Myocarditis and pericarditis loomed large for the panel. The CDC warned in early June that it has been getting increasing reports of these events after vaccination with the Pfizer and Moderna mRNA-based vaccines, particularly in young males.

While cardiac MRI is very sensitive and it doesn’t take much of an insult to get a positive scan, Meissner argued, the long-term consequences are unknown. “Will there be scarring? Will there be a predisposition to arrhythmias later on? Will there be an early onset of heart failure? I think it’s unlikely, but we don’t know that. Before we start vaccinating millions of adolescents and children, it is so important to figure out what the consequences are.”

On the other hand, it’s not even clear yet that this is a causal association, Rubin cautioned. Also, “we’re not going in with a blank slate with a new vaccine to kids. We’re going in with a gigantic base of experience now in adults.” While that data has suggested rare side effects, it hasn’t shown worrisome common side effects, he pointed out.

Most panelists argued that longer follow-up wouldn’t really provide better answers on infrequent events, although there were dissenters who thought a minimum of 6 months or 1 year of data would be best to catch longer-term risks and provide more confidence for the public.

Most also agreed that trials with around 1,500 children, perhaps more heavily weighted toward the younger age strata, would be sufficient. Even doubling the number wouldn’t catch rare events. For that, it’s going to be all about post-marketing surveillance and watching what happens in longer follow-up coming in from the trials and real-world use in the older teens and young adults.

“The concerns we’re talking about now manifest in the fairly short-term after vaccination,” noted Fink, pointing out the need to carefully weigh what additional information would be gained against the harms of unnecessarily delaying access. “We have to be realistic.”

There are robust near real-time surveillance systems in place for post-marketing safety evaluation, FDA presenters noted, including the Vaccine Adverse Event Reporting System (VAERS). Active monitoring from the FDA BEST system via claims and electronic health records from major nationwide partners also includes millions of children.

The Advisory Committee on Immunization Practices will meet June 18 to consider updated data on myocarditis and assess vaccine risks and benefits in adolescents and young adults.

Moderna has the KidCOVE trial underway testing its vaccine in children ages 6 months to 11 years. It told CNN that data on those as young as 5 years should be available by September or October. Pfizer’s combination dose-ranging to phase III trial has also dosed its first participants in the 6-month to 11-year age range.






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