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E&C Leaders Release FDA User Fee Package

On Wednesday, bipartisan leaders of the House Energy and Commerce Committee released a legislative proposal to reauthorize the Food and Drug Administration’s (FDA) ability to collect fees from drug, biosimilar, and device manufacturers for five years.  Additionally, the bill contains several policy riders that would give the FDA more control over the accelerated approval program, promote diversity in clinical trials, and reinstate a ban on electric shock devices for aggressive behavior, among other items.  The Health Subcommittee is expected to markup the user fee bill next Wednesday, with the goal passing the legislation in Congress by August.

FDA Approves Marketing of New Alzheimer’s Test

The FDA on Wednesday approved the marketing of an in vitro diagnostic test for early detection of amyloid plaques associated with Alzheimer’s disease.  Produced by Fujirebio Diagnostics, the test works by measuring the ratio of certain proteins in the fluid that surrounds the brain.  In a press release, the FDA said the availability of an in vitro diagnostic test could eliminate the needs for PET scans, which are time-consuming and expensive.  In a clinical study, the test detected Alzheimer’s disease in 97% of people who had amyloid plaques present in a PET scan.  The National Institute of Health (NIH) estimates that over six million Americans may have Alzheimer’s disease.

Survey: Most Parents Will Wait to Get Young Kids Vaccinated

18% of parents of children under 5 say they’ll get their kids vaccinated for COVID-19 as soon as a shot is authorized, according to a survey from the Kaiser Family Foundation.  Another 38% say they’ll take a “wait and see” approach before getting their kids vaccinated, while 56% want more information about vaccine safety and efficacy before making a decision.  Delays in FDA authorization of vaccines for young kids also left parents with mix feelings, with 22% saying the delays have made them more confident in the vaccine and 13% sayings the delays have made them less confident.  The survey was conducted in mid-April 2022, right before Moderna filed to authorize its vaccine for kids under 5 with the FDA.

Rent-A-Cops Arrive on Capitol Hill to Provide Security

To help address staffing shortages, the US Capitol Police (USCP) recently started deploying private security guards around the US Capitol Complex.  The private officers will wear grey dress pants and a navy-blue blazer rather than the police uniform and will be unarmed.  According to the USCP, the private officers will be stationed inside secure building like the House and Senate office buildings and will help augment existing patrols.

ICYMI: Jazz in the Garden Returns to National Mall on May 20

In two weeks, Jazz in the Garden will return to the National Gallery of Art Sculpture Garden along the National Mall.  The free concert series is a favorite summer tradition in Washington, DC, and this year’s series is set to features several genres including jazz, Afro-Brazilian, and bluegrass.  The series was closed during summer 2020 and was only open on a limited basis for summer 2021.  Guests will be required to register for the concert in advance.

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.

People will only need annual COVID-19 booster shots after getting their third vaccine dose, according to a top Food and Drug Administration (FDA) official at the 2022 Innovation in Regulatory Science Summit in January 2022.  Since then, however, mounting evidence over waning immunity plus the potential of a new wave of COVID-19 are feeding calls for people to get their fourth vaccine doses sooner rather than later.  Does that mean Americans can expect to get a second booster shot in the coming months?

First, some Americans are already able to get a second booster shot.  According to guidance from the Centers for Disease Control and Prevention (CDC), people ages 12 years and older who are moderately or severely immunocompromised should receive a total of four mRNA vaccine doses.  This includes transplant patients and those undergoing chemotherapy for cancer.

Drug manufacturers are already asking for approval on second boosters for additional populations.  In mid-March, Pfizer and Moderna submitted applications to the FDA for an emergency use authorization (EUA) for a second booster dose of their respective COVID-19 vaccines.  While Pfizer is specifically seeking an EUA for adults over age 65, Moderna is requesting an EUA for anyone over 18 years of age.

The submission of both applications came just days after Pfizer CEO Albert Bourla said a fourth vaccine dose will probably be needed for everyone.

• One reason for this is mounting data that shows protection acquired from a third COVID-19 vaccine dose wanes over time.  According to CDC data, a booster shot’s effectiveness in protecting against hospitalization dropped from 91% to 78% between August 2021 and January 2022 – a timeframe that includes both the Delta and Omicron variants.
• Another reason for a fourth shot is a need to protect Americans ahead of a new wave of COVID-19 cases.  In recent weeks, a new Omicron subvariant known as BA.2 has driven an increase in cases across Europe, which many experts say could foreshadow an increase in cases in the US within the coming weeks.  Although BA.2 is roughly 30% more transmissible than the original Omicron strain, it does not appear to be more severe or lead to more hospitalizations.  While overall COVID-19 case numbers are still trending downward in the US, 10 states have reported an increase in case numbers over the last 14 days.

Due to these concerns over waning immunity and growing case numbers, nearly a dozen countries including Australia, Belgium, Denmark, Israel, Poland, Sweden, and the United Kingdom have already begun offering fourth doses, albeit eligibility is limited to seniors and medically vulnerable people in most cases.  Additionally, reports suggest the FDA could authorize second boosters for all adults over age 50 as soon as March 29.  However, that doesn’t necessarily mean the government will follow suit in recommending a fourth mRNA vaccine dose to every individual age 12 and up who’s already cleared to get a third dose anytime soon, as a couple issues stand in the way.  These include:

• Regulatory approval.  The FDA’s vaccine advisory committee will meet on April 6 to discuss the need for additional COVID-19 booster shots.  However, the advisory panel will NOT be reviewing any EUA applications from Pfizer or Moderna or taking a vote on recommendations – instead, the committee will discuss the timing and populations for additional doses in the coming months.  The April 6 agenda is a sign of the federal government’s cautious approach to boosters, which means it might take some time for federal regulators to sign off on additional doses, especially for the broader population.  In September 2021, for instance, a CDC advisory panel declined to recommend third doses for people who work in “high-risk” settings like health care practitioners and teachers – a decision which was ultimately overruled by CDC Director Rochelle Walensky.
• Data.  Even though a number of countries have already cleared fourth shots for certain populations, the jury’s still out on whether a second booster will make a difference for non-elderly adults who are not considered medically vulnerable.  Preliminary results from a study involving 154 health care workers in Israel found that a fourth mRNA dose is only “partially effective” in protecting against the Omicron variant.  Without any strong evidence of the effectiveness of a fourth shot, US regulators are likely to continue to take a cautious approach on recommending additional boosters for the broader population.
• Funding.  Lawmakers dropped $15 billion in additional COVID-19 funding from the Fiscal Year (FY) 2022 omnibus appropriations bill, and so far, congressional leaders are locked in a stalemate on passing separate legislation on additional COVID-19 support.  Without additional funding, Biden administration officials have warned that they won’t have enough money to purchase a potential fourth vaccine dose for even 70% of all Americans.  And barring additional funding, the federal government will no longer be able to cover the cost of vaccinations for uninsured people starting on April 5, which means uninsured immunocompromised Americans may not be able to afford a booster if they need one.

Ultimately, the trajectory of the COVID-19 pandemic may ultimately inform whether additional boosters are necessary for Americans, and in turn, whether Congress decides to allocate enough money to pay for additional vaccine doses.  While White House Chief Medical Advisor Anthony Fauci has acknowledged that the BA.2 subvariant is likely to cause cases to rise in the US, he doesn’t anticipate new cases will culminate in a major surge that results in high levels of hospitalizations.

Indeed, a good portion of the US population has acquired some degree of immunity through infection, vaccination, or both over the last two years of the pandemic, which could protect Americas from the worst consequences if case numbers continue to rise over the next few weeks.  However, if hospitalizations suddenly spike across multiple populations, it may be too late for the federal government to act swiftly on additional boosters.

The current public health emergency (PHE) is set to expire on April 16.  While the Biden administration is likely to extend the PHE, administration officials have yet to comment on their specific plans.  Uncertainty over the end of the PHE has fueled conversations over what the implications would look like for temporary health care policies that expire once the PHE officially concludes.

Blog posts from the last two weeks have looked at how the end of the PHE would affect Medicare’s temporary telehealth waivers and Medicaid coverage.  This week’s blog post focuses on how ending the PHE would impact the Food and Drug Administration’s (FDA) emergency use authorizations (EUAs).

Background:  An EUA allows the FDA to authorize unapproved medical products or unapproved uses of approved medical products – like vaccines and treatments – to be used to diagnose, treat, or prevent serious or life-threatening diseases in cases where there are no adequate, approved, and available alternatives.  Since the start of the COVID-19 PHE on January 31, 2020, the FDA issued hundreds of EUAs for pharmaceutical and medical devices related to COVID-19.

How? Section 564 of the Federal Food, Drug and Cosmetic (FD&C) Act allows the FDA to issue four different types of EUAs during a PHE for diagnostics, respiratory equipment, medical devices, and drugs/biologics.  However, the FDA still has the authority to issue an EUA outside of a PHE thanks to the Pandemic and All-Hazards Preparedness Reauthorization Act (PAHPRA) of 2013, which grants Department of Health and Human Services flexibility to declare that “circumstances exist” outside of a PHE to allow EUAs to be issued.

What does the end of the PHE mean for the EUAs?  Unlike the other temporary authorities related to telehealth and Medicaid, all EUAs that are issued by the FDA remain in effect until the FDA withdraws the EUA declaration.  For instance, the EUA declarations issued for the Zika and Ebola pandemics were never withdrawn and are currently in effect, even though their respective PHEs have long since expired.

However, one FDA policy, separate from EUAs, will expire at the conclusion of the PHE – enforcement discretion.  This policy allows the FDA to waive enforcement of its usual requirements for pre-market approval to allow drug products to be modified for additional uses without full approval from the agency.  In contrast, drug products approved via an EUA must still meet specific criteria on safety and effectiveness.  Once the PHE ends, the FDA will revert to its regular enforcement policies, and all products where enforcement discretion once applied must then meet all standard FDA legal requirements in order to continue to be sold in the US.

Planning for a Post-EUA Future

Unlike the EUAs for Zika and Ebola treatments, the FDA has communicated that it doesn’t want the COVID-19 EUAs to stick around forever and manufacturers should expect an “eventual resumption of normal operations.”  To this end, the FDA issued two draft guidance documents in late December to help facilitate a return to normal:

• Transition Plan for Medical Devices Issued EUAs During the COVID-19 Public Health Emergency.  This provides a plan for manufacturers of drug products that received an EUA to seek formal market access (including a three-phase transition process with specific timelines for complying with regulations and submitting market application).  It says HHS would issue an advanced notice of termination of the EUA declaration 180 days in advance.
• Transition Plan for Medical Devices that Fall Within Enforcement Policies Issued During the COVID-19 Public Health Emergency.  This would also allow a three-phase transition process for manufacturers to seek formal market access decisions for modified use of their products, or to revert their products back to previous authorizations.

Uncertain Future for Stakeholders

On February 22, the FDA held a webinar for industry stakeholders about its draft guidance documents on its post-pandemic transition plans, and like their counterparts in telehealth and Medicaid, the stakeholders from the pharmaceutical and medical device industries had a lot of questions.

• Of the four EUA declarations, three are specific to devices, and it’s not clear if the agency will withdraw those EUAs all at once or at different times.
• The webinar did not offer stakeholders a clear answer on whether HHS issues the advance notice on withdrawing the EUA declarations first, or FDA will finalize its two guidance documents on its transition plans.   Instead, FDA staff told attendees that whatever happens first depends on the course of the pandemic.  If hospitalizations continue to decline and stay low, HHS may pull the EUA declarations first; otherwise, finalization of the guidance documents could come sooner.
• The FDA says more guidance is on the way, but it’s unknown when it will be released.  According to FDA staff, this would pertain to the types of data FDA will consider when transitioning a drug product from an EUA to formal market access, such as how real-world evidence will be considered.

While pharmaceutical industry stakeholders can feel relieved that EUAs won’t expire with the end of the PHE and that the FDA is making plans for a post-pandemic world, question about what that world will look like simply add to the narrative that the federal government’s take on health care policies once the PHE ends need significant refinement.

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.