Pfizer asks for endorsement of 2 doses of vaccine for children under 5

Pfizer and its partner, BioNTech, asked the Food and Drug Administration (FDA) on Tuesday to authorize two doses of its coronavirus vaccine for children under 5, as the companies continue researching whether three doses would be more effective for this age group.

In an extremely rare move, federal regulators pressured companies to submit the application, even though two doses failed to produce the expected immune response among 2- to 4-year-olds in a clinical trial. Only children between 6 months and 2 years of age demonstrated an immune response comparable to that of adolescents and young adults, the criterion for a successful trial.

The emergency authorization request comes at a time when the highly contagious omicron variant has caused a record number of infections. The under-five group includes more than 19 million children, the only Americans not yet eligible for vaccination.

The disappointing results of the trial, announced in December, prompted the companies to test a third low dose of the vaccine in this age group. But rather than waiting until the end of March for the results, federal regulators decided to encourage companies to apply for authorization for a two-dose regimen now, in hopes of getting a head start on the vaccination effort.

In meetings on the strategy, government officials argued that two doses were shown to be safe, even if they did not produce an immune response across this age group, according to several people briefed on the discussions. Children in the study received one-tenth of the dose given to adults.

If the children can get an initial injection this month, some officials reasoned, they will be ready for a third dose when researchers have the results of the three-dose trial, which they hope will be successful. The first two doses would be spaced three weeks apart, followed by a third two months after the second.

Janet Woodcock, the FDA’s interim commissioner, and Peter Marks, a member of the regulatory agency that oversees the vaccine office, said on Tuesday it was important to act quickly given the surge in omicron cases, which has already peaked in many parts of the world. USA, and the likelihood that other variants will emerge.

An emergency meeting of the FDA’s external expert advisory group is scheduled for February 15, at which time the request will be discussed and a recommendation will be made. Paul A. Offit, a member of the group and director of the Vaccine Educational Center at Children’s Hospital of Philadelphia, suggested that regulators may be short-circuiting the normal process without clear justification.

“It makes no sense for us to approve a two-dose vaccine on the assumption that the third dose would compensate for the deficiencies of the two,” he said.

Albert Bourla, president and CEO of Pfizer, said in a statement that “Ultimately, we believe that three doses of the vaccine will be needed for children aged 6 months to 4 years of age to achieve high levels of protection against current and potential future variants.” But he said that if two doses are authorized in the meantime, “parents will have the opportunity to start a series of Covid-19 vaccinations for their children while they await potential authorization for a third dose.”

The Pfizer and BioNTech study of younger children was intended to measure immune responses, not vaccine effectiveness, in preventing infections or severe cases of Covid-19. Because some test children became infected, however, the researchers got indications of the vaccine’s effectiveness in warding off the virus, said two people familiar with the study. A similar fact occurred in the companies’ study of their vaccine in children aged 5 to 11 years, which overlapped with an overwhelming wave of the delta variant.

A person familiar with the data, who spoke on condition of anonymity, said children ages 2 to 4 who received two injections were infected at a 57% lower rate than children in the placebo group. Children aged 6 months to 2 years who received injections were infected at a 50% lower rate than the placebo group. There were fewer than 100 cases of symptomatic infection — a tiny fraction of the total number of participants — and the margins of error were wide, this person said.

The data also suggested that the vaccine protected children better against infection with the delta strain than the micron. Omicron is better than delta at escaping the protection of Pfizer and Moderna vaccines in adults.

The regulators’ strategy appeared to be based in part on the likelihood that Pfizer’s three-dose trial would succeed. Several experts, including Dr. Yvonne Maldonado, a professor of pediatric infectious diseases at Stanford University, said the history of vaccines suggests that a third dose would actually boost the immune response.

“There is almost no conceivable hypothesis that a third dose would be worse,” said Maldonado, one of the principal investigators on Pfizer’s pediatric vaccine trials at Stanford. “At worst, it couldn’t be otherwise. So maybe two shots are the best we’re going to get.”

If the FDA follows through with the authorization, a separate advisory panel from the Centers for Disease Control and Prevention will vote on whether to support the action. Dr. Rochelle Walensky, director of the CDC, will then decide whether the agency should recommend injections as official policy.

Public deliberations by regulatory agency expert committees can influence vaccine acceptance, underscoring the importance of a clear and open discussion of what the data reveals.

If doses are allowed, families can still tread cautiously. Three in 10 parents of children under age 5 now say they intend to have their children vaccinated against the coronavirus as soon as vaccines are available for that age group, according to research published Tuesday by the Kaiser Family Foundation.

Dr. Moira Szilagyi, president of the American Academy of Pediatrics, said in a statement Tuesday that she is excited that “we may be one step closer” to vaccines for younger children.

Last month, “we recorded the highest number of Covid-19 cases among children since the beginning of the pandemic. More than 3.5 million new cases in children were reported in January 2022 alone,” she said. She called for “a transparent, data-driven process” in processing the companies’ request.

The CDC released a survey in late December that showed very few reports of serious problems among children ages 5 to 11 who received Pfizer’s immunizer.

But the pace of vaccination for the 28 million American children in that age group was even slower than public health experts feared. Only about 30% of children in this group received at least one dose, according to CDC data.

A study released by the agency of hundreds of pediatric hospitalizations in six cities last summer found that nearly all of the children who became seriously ill had not been fully vaccinated.

Translated by Luiz Roberto M. Gonçalves.