Pfizer and FDA pull back from plan to expedite review of Covid-19 vaccine in young children

Plans to attempt to authorize the Pfizer/BioNTech Covid vaccine for children under 5 before full data are available appear to have run aground.

The Food and Drug Administration on Friday canceled a key meeting of its vaccines advisory committee that had been slated for next Tuesday to discuss the submission, saying that the delay “will give the agency time to consider … additional data.”

Both the FDA and the companies suggested the application for authorization won’t proceed until there are data showing how well the vaccine works after a third dose. Those data should be available in early April, the companies said.

“For the next few months, while these additional data are gathered, parents will have to rely on what they have come to do well, which is that they’re using masking procedures and making sure they’re vaccinated and taking those types of precautions with their youngest children,” said Peter Marks, the director of the FDA’s Center for Biologics Evaluation and Review.

The vaccine was originally tested in a two-dose regimen, with each dose containing one-tenth of the amount of vaccine as an adult dose. But Pfizer announced late last year that in a clinical trial of children aged 2 to 4 years old, two doses failed to generate antibody levels on par with those seen in people aged 16 to 25 after two shots. Paradoxically, two doses given to infants aged 6 months to 23 months did appear to generate adequate protection.

The FDA would not specify why it no longer planned to consider authorizing the vaccine for children 6 months to 4 years of age while the clinical trial in that group was still underway. But in a briefing for journalists on the decision, Marks appeared to hint that it was because the data provided by the companies weren’t strong enough to warrant early authorization.

“The data that we saw made us realize that we needed to see data from a third dose in the ongoing trial in order to make a determination that we could proceed with doing an authorization,” he said. “I think parents can feel reassured that we have set a standard by which we feel that if something does not meet that standard, we can’t proceed forward.”

Parents eager to vaccinate their young children seemed to take cold comfort from the fact that they won’t soon be able to start the vaccination process for those children, with a number expressing their displeasure on social media.

“Today’s announcement is a travesty for millions of families and children across the country. mRNA vaccines have been proven to be safe for children, and withholding them during the pandemic is unconscionable,” said Protect Their Future, which describes itself as a grassroots group of physicians, parents, and activists who have been advocating for accelerated access to Covid vaccines for young children.

However, others believe that the FDA made the right decision. A number of experts had earlier questioned the wisdom of moving ahead before the Pfizer/BioNTech trial is complete, suggesting it would undermine confidence among parents who are worried about vaccinating their children with such a new vaccine.

Norman Baylor, who formerly held Marks’ position at the FDA, was one of those who felt it would be ill-advised to start using the vaccine in children under 5 before the trial had concluded.

“I would suspect that whatever data they had that was supposed to overcome the lackluster immune responses in the 2-4 year olds was either deemed to be insufficient (perhaps by the FDA reviewers) or inconclusive,” Baylor, who is now president and CEO of Biologics Consulting, told STAT in an email. “Most of us were saying all along that they should wait until the third-dose data are available and evaluated before making a decision to authorize the vaccine in children below the age of 5. Even Pfizer stated last week that 3 doses would be needed.”

The companies said on Feb. 1 that they were asked by the FDA to submit an application for the use of a two-dose vaccine in children 6 months to 4 years old. Data on a third shot would be submitted to regulators when they became available in the spring. Some outside experts have characterized this strategy as aggressive and unusual, and have worried it could backfire by making some parents less inclined to vaccinate their kids.

But Marks insisted that given the size of the Omicron wave and the impact it was having on young children, that the FDA had a responsibility to act urgently.

“We had days when we were getting above three-quarters of a million cases a day of Omicron, and we started to see a tremendous number of children affected by Omicron,” he said.

The clinical trial measured immunogenicity — if the vaccine triggered similar responses in young children as it does in older teens and young adults. But it is also gathering vaccine efficacy data — comparing rates of infections among the children who’ve been vaccinated to those in the placebo arm of the trial.

The trial is far smaller than those that were conducted in adults; only 2,447 children were enrolled. In some circumstances, that might not be large enough to generate a vaccine efficacy estimate. But it would appear there have been enough infections within the trial that coming up with that answer may be possible. “I think that’s probably a safe assumption,” Marks said of the possibility the trial will generate an efficacy readout.

He said the FDA has been constantly evaluating the data that comes in and adjusting its strategy accordingly. “Once the next tranches of data come in … we’ll be looking at them in an expeditious manner.”

Some sources, who spoke on condition of anonymity, said data from Pfizer to the FDA had come in late, and FDA staffers may have needed more time to vet them. It’s also possible new issues emerged with those data. The FDA normally posts extensive briefing documents prepared by both vaccine manufacturers and by FDA staff two working days before a scheduled meeting, although it does not have to meet this deadline. As of Friday morning, none was published.