FDA

Is Public Pressure Impacting the FDA’s Vaccine Review Strategy?

by Matt Gontarchick

Parents of young children are frustrated and mad.  While adults have been able to get third and even fourth COVID-19 vaccines doses for some time now, children under six years are still unable to get their shots while the rest of society reverts to a pre-pandemic normal.

Anger among parents hit a boiling point last week when White House Chief Medical Advisor Dr. Anthony Fauci confirmed reports that the Food and Drug Administration (FDA) will not approve vaccines for kids under 6 until it can simultaneously review and approve vaccines from both Pfizer and Moderna.

However, less than a week later, FDA officials seemingly changed course when they announced that they may move forward on reviewing Moderna’s vaccine without waiting for Pfizer’s application – meaning that young children could get vaccinated as soon as June.  What caused the FDA to take an about face on its vaccine review strategy?

At the time of Fauci’s comment on April 21, Moderna was poised to begin applying for an emergency use authorization (EUA) within the next week or two, as initial data showed its vaccine generated strong protection in kids.  News that the FDA could soon begin reviewing Moderna’s EUA application set off a sign of relief among parents, who have had to contend with constant delays in the race to get young kids vaccinated.

However, Pfizer’s vaccine for children under 5 is still undergoing clinical trials for a three-dose regimen after results from a two-dose regimen did not yet provide strong protection against the virus, and it’s not clear when Pfizer will be ready to submit its data.  By waiting to review vaccines from both companies, the timeline for getting shots into kids’ arms faced a decent chance of getting extended once again.

What was the FDA thinking?  According to reports,  FDA officials wanted to review vaccines from Moderna and Pfizer simultaneously because approving both at the same time would be less confusing for parents than approving each at different times.  Additionally, FDA officials were worried about a possible backlash from parents if the agency approved Moderna’s vaccine first and Pfizer’s several week later when Pfizer’s vaccine demonstrated stronger efficacy. 

Despite the FDA’s rationale, reports that federal officials were delaying the review process once again elicited a strong backlash from concerned parents and lawmakers.  In the days following Fauci’s comments, lawmakers wrote to the FDA requesting an explanation as to why vaccines for young children were being delayed again, and parents and pediatricians launched an advocacy campaign to urge the FDA to review each vaccine application “at the earliest opportunity.”

Did Public Pressure Make a Difference?

The FDA finally changed its tune on April 29, when a top official announced the agency will consider vaccine applications as soon as they are ready.  While it is not clear if the FDA shifted its strategy purely in response to political and public pressures, it wouldn’t be first time public pressure might have made a difference. 

In mid-2021, the FDA appeared to be on track to approve the vaccine for children aged 5-11 by early fall, just in time for the start of school.  However, in July, the FDA asked Pfizer and Moderna to expand the size of their clinical trials for children to make sure they could detect potentially rare side effects, namely myocarditis, or heart inflammation – effectively pushing the timeline for vaccine approval out to winter 2021 or early 2022.  This drew sharp criticism from parents and pediatricians, who argued that complications from COVID-19 posed a greater threat to kids than myocarditis.

The strongest sign of pressure on the FDA came in the form of an August 2021 letter from the American Academy of Pediatrics (AAP) that called on agency to stick to its original timeline for collecting data and authorize vaccines for children under 12 as soon as possible.  A month after the pediatricians weighed in, the FDA issued an unprecedented statement saying that it would no longer wait for additional follow-up data from expanded clinical trials to made a decision on an EUA and stick to its original timeline. 

Like many things with the pandemic, nothing is certain as the FDA determines how it will review vaccines for younger children.  Moderna only began to submit data for its EUA on April 28, and the FDA has laid out a tentative schedule that leaves open the possibility that kids under 6 could get their shots sometimes this June.  However, things could still change. An FDA official say the agency could still review EUA applications from Moderna and Pfizer simultaneously if both are filed less than a week apart, and many parents and pediatricians say June is still too long of a wait for young kids to get vaccinated, especially considering that the review process for other age groups took less time. 

However, actions undertaken by the FDA last fall and last week suggest that the agency isn’t immune to public pressure.  This sets up a precedent where advocacy could sway the FDA review process in the future – for better or for worse.

FDA

When Can Kids Under 5 Get Vaccinated?

by Matt Gontarchick

An average 672 children per day last week were admitted to the hospital with COVID-19 last week, the highest number since the COVID-19 public health emergency began.  Surging case numbers are also causing schools to close and temporarily revert to virtual learning.  While children ages 5-17 can be vaccinated for protection against COVID-19, this currently isn’t an option for children under 5 years of age.  Even though pharmaceutical companies have been working on vaccines for younger children, some bumps in the road means the timeline for getting this cohort vaccinated hasn’t exactly been static.

Pfizer’s Swing and a Miss

Pfizer was the first COVID-19 vaccine developer to begin testing vaccine in children under five.  For its late-stage clinical trial, Pfizer administered two 3-microgram doses three weeks apart, which is less than one-third of the dose given to older children. 

Pfizer initially hoped to submit data on the efficacy of its vaccine in children in the first quarter of 2022, but an announcement from the company on December 17, 2021 signaled a delay in the timeline young children can get vaccinated.  According to Pfizer, its 3-microgram dose yielded high level of protection in children ages 6- to 24-months-old but did not generate a sufficient level of protection in children ages 2 to 5. 

Now, Pfizer is amending its clinical trial to add a third 3-microgram dose for children 6 months to 5 years of age.  If the updated trials are successful, Pfizer says it will submit data to the Food and Drug Administration (FDA) in April, which pushes the timeline for young children to get the company’s vaccine back by a few months. 

What about Moderna?

News that Pfizer is extending its trial left parents of younger kids understandably upset.  Fortunately, Pfizer is not the only company developing vaccines for children.  Moderna is currently conducting trials in children ages 6-months to 5-years-old, and the company expects to have results available by the end of January, which means the FDA could provide emergency approval as soon as late February or early March 2022.  Moderna is also testing younger children with a higher-microgram dosage than Pfizer, which presumably increases the likelihood that Moderna’s vaccine will yield an adequate immune response.

Children’s Risk Still Very Low

Even though it will probably be a few more months until younger children can get their shot, parents should feel some assurance that young children’s risk of complications from COVID-19 is extremely low.  The COVID-19 death rate for children ages 0-17 in the US is 0.1%, by far the lowest for any age group (in comparison, the death rate for US adults ages 50-64 is 1.39%). 

While pediatric hospitalizations related to COVID-19 are at a record-high, many of these hospitalizations are incidental, meaning children are being hospitalized with, but not for COVID.  An example of an incidental pediatric hospitalization could be for a child who falls on the playground, is admitted to the hospital for a broken bone, and only tests positive as a part of routine screening.

Additionally, young children who are infected with COVID-19 overwhelmingly exhibit mild symptoms or are asymptomatic, with hospital stays rare.  And while it is possible that young children can become COVID-19 long-haulers, studies are increasingly showing that long-COVID in kids is also rare. 

News of Pfizer’s clinical trial results was certainly disappointing for parents.  But with the possibility of better clinical trial results in the future plus strong data on the low level of risk for young children, parents should have a somewhat optimistic outlook heading into the third year of the pandemic.

FDA

When Are Kids Going to Get Vaccinated?

by Matt Gontarchick

Parents are mad.  While grown-ups have been eligible for COVID-19 vaccines for almost a year, there currently aren’t any options for children under 12.  This is especially concerning for many parents as the kids return to school amid a nationwide surge in cases.

A Different Process

On September 20, Pfizer/BioNTech released data showing its mRNA vaccine is safe and effective in children aged 5-11.  As the Food and Drug Administration (FDA) has fully approved the vaccine for individuals aged 16 and older and Pfizer/BioNTech vaccine is still available to individuals aged 12 to 15 through emergency authorization, why is the approval process taking so long for children?   

  • More data.  Earlier this year, FDA asked Pfizer/BioNTech and the other vaccine developers to provide six months of follow-up data for all clinical trial participants.  In comparison, the approval process for adults only required two months of follow-up data. 
  • More scrutiny.  Unlike the emergency use authorization (EUA) for adults, FDA doesn’t just rely on a company’s summary of the clinical trial data for children’s vaccines.  The agency looks at individual reports from every child, including data on side effects and blood tests. 
  • Biological differences.  Kids aren’t simply smaller adults.  Children have more active immune systems than grown-ups, which means scientists need to ensure they’re providing the right dosage.  Pfizer/BioNTech has specifically been testing children aged 5-11 with a two-dose regimen administered three weeks apart.  Each dose contains 10 micrograms, which is about a third of the dosage used for individuals aged 12 and up.

Pressure Grows for FDA to Speed Up Timeline

Earlier this year, it appeared that FDA would be able to approve vaccines for children aged 5-11 by early fall, just in time for the start of school.  However, signs that the approval timeline would extend first appeared in July when FDA asked Pfizer and Moderna to expand the size of their clinical trials for children to make sure they could detect potentially rare side effects, namely myocarditis, or heart inflammation.  These changes caused many health experts to revise their predictions on a timeline for approval for EUA, with some saying that the FDA would not make a decision until winter 2021 or early 2022.

The prospects of a longer timeline combined with a nationwide surge in cases sparked panic among many parents of younger children.  While COVID-19 poses a low risk for healthy kids, there is a justifiable concern about immunocompromised children as well as the ability for kids to pass the virus onto vulnerable adults.  As a result, some parents are even looking for doctors to skirt the rules and vaccinate their children, while others are signing their kids up for clinical trials, even though it’s unknown whether their child will be receiving the vaccine or a placebo.

Pressure from Pediatricians: The American Academy of Pediatrics (AAP) urged the FDA in an August 5  letter to “continue working aggressively towards authorizing safe and effective COVID-19 vaccines for children under age 12 as soon as possible” due to the threat posed by the Delta variant.  Specifically, AAP indicated that a two-month follow-up period to collect safety data is sufficient, as opposed to the six-month period FDA initially requested.  AAP also noted that reported cases of myocarditis in children who are receive mRNA vaccines like Pfizer/BioNtech’s are “extremely rare.”

The FDA is listening and took the rare step of publicly responding to the concerns around approving a COVID-19 vaccine for children on September 10. .  In addition to vowing to adhere to strict safety standards, FDA stated clinical trials are required to have a “follow-up period for safety data of at least about two months,” indicating a change from the previously requested six-month follow-up period.

The Timeline, Revised

With the FDA apparently open to a shorter follow-up period for safety data, what does the approval timeline look like now?  At the the Morgan Stanley Global Healthcare Conference 2021 on September 14, Pfizer CEO Albert Bourla laid out a new estimated approval timeline for children aged 5-11. 

  • Pfizer to have all safety and immunogenicity date in late September (topline results were released on September 20).
  • Pfizer to file for EUA in early October.
  • FDA to approve EUA within 3-6 weeks, meaning children aged 5-11 could get their shots as soon as late October or early November. 

Bourla also said Pfizer will likely have enough data on how well its vaccine works on children under 5 years of age as early as the end of October, putting that vaccine on the path for EUA by the FDA by the end of the year. 

This is reassuring news for parents of kids aged 5-11, to potentially have a vaccine available by Halloween than, say, early 2022.  But let’s not get our hopes up as COVID-19 has proven itself to be an incredibly unpredictable virus, and changing conditions could cause scientists and regulators to shift their approval considerations once again.

FDA

What’s Taking FDA So Long to Fully Approve Pfizer’s COVID-19 Vaccine?

by Matt Gontarchick

It took the Food and Drug Administration (FDA) just three weeks to issue an emergency use authorization (EUA) for Pfizer’s COVID-19 vaccine in December 2020 when Pfizer submitted the request.  In contrast, it’s been over two months since Pfizer initiated a “rolling submission” of its biologics license application (BLA) for its vaccine on May 7, and FDA has yet to comment on its timeline for approval.  Amid growing calls for FDA to fully approve Pfizer’s vaccine, what’s making the review process take so long?

Why the Push for Full Approval?

Many people believe full approval of Pfizer’s COVID-19 vaccine will help get more shots into arms, which is seen as vital to protecting Americans from the rapidly spreading Delta variant.  According to data from the Centers for Disease Control and Prevention posted on July 6, the Delta variant makes up 51% of new COVID-19 cases in the US.  Additionally, studies show the Delta variant is at least 40% more transmissible than the Alpha variant, which was previously the country’s dominant variant.  The surge in the Delta strain comes as many Americans remain vulnerable to COVID-19, as only 67% of Americans have received at least one COVID-19 shot, and the pace of vaccinations has dropped off considerably in recent weeks. 

Full approval of the COVID-19 vaccine is one way public health experts believe could convince more Americans to roll up their sleeves, which addresses vaccine hesitancy, a sentiment echoed by several major elected officials.   In June, President Joe Biden said going from “temporary approval to full approval” would “increase the number of people” willing to get vaccinated.  Similarly, Arkansas Governor Asa Hutchinson, whose state has some of the nation’s lowest vaccination rates, remarked in June that full approval is needed to combat vaccine hesitancy.  According to a Kaiser Family Foundation poll from May 2021, 32% of unvaccinated adults said full approval of one of the currently authorized vaccines would make them more likely to get vaccinated.

Furthermore, fully approving the vaccine will allow for more businesses and organizations to mandate the COVID-19 vaccine, which could help increase vaccination rates.  While several hospitals and health systems such as Houston Methodist and Trinity Health have mandated the vaccine for their employees, some health systems like Beth Israel Leahy Health in Boston are holding off until a vaccine is fully FDA-approved.  Even though lawsuits against vaccine mandates have so far held up in court, many employers and organizations seem to be holding off on mandating  employees to get the vaccine out of fear of litigation.   Even the US Army has communicated to servicemembers that vaccination won’t be mandated until “full FDA licensure.”

What’s the Hold Up?

The reason for FDA’s longer process for fully-approving Pfizer’s COVID-19 vaccine is due to the fact that the business of issuing a BLA is more intensive than an EUA.   For an EUA to be issued, companies need to provide the FDA data that demonstrates efficacy and safety from a Phase 3 trial with a median follow-up period of at least two months.  In contrast, a BLA requires FDA to look through at least six months of clinical trial data as well as a close examination of the company’s manufacturing process, both of which take additional time.  Dr. Paul Offitt, a member of FDA’s Vaccines and Related Biological Products Advisory Committee,  commented in December 2020 that Merck’s BLA submission for its 70,000-person rotavirus vaccine trial contained enough pages to exceed the height of the Sears Tower, a 1,450-foot skyscraper in Chicago currently known as the Willis Tower.

There are benefits for drug manufacturers in getting their products fully approved.  According to former FDA Commissioner Dr. Robert Califf, a BLA would allow Pfizer to being marketing its vaccine directly to consumers.  Additionally, full approval would open the door to Pfizer increasing the price of its vaccine post-pandemic, potentially generally billions of dollars for the company.

When Will the Vaccine Be Fully Approved?

Unfortunately, FDA has yet to shed any light on its timeline for fully approving the Pfizer vaccine.  In late June, an FDA spokesperson  told The Hill that the agency “cannot comment on individual applications before it.”  More recently, the FDA told Army Times on July 2 that timelines for approval “may vary depending on a number of factors.” 

While fully approving a vaccine normally takes between 8-12 months, there is reason to believe Pfizer will receive a decision from the FDA soon. Former FDA scientist Jesse Goodman said in June that the FDA might not complete its review process for another 3-4 months, meaning a BLA might not come until  September or October.  Notably, Goodman cautions against fully approving the vaccine too quickly, as it could “undermine confidence” in the vaccine. 

Ultimately, FDA is in a tough position.  As a full review of the Pfizer vaccine continues, the agency must strike a balance between ensuring the American people can benefit from a fully approved vaccine in a timely manner without giving off the sense that the BLA was issued too quickly.  Absent any communication from FDA, however, vaccine observers have no choice but to sit and wait.