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

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.

What Happened, What You Missed: July 5-9

CDC, FDA Counter Pfizer on Need for Booster Shot

On July 8, the Centers for Disease Control and Prevention, and the Food and Drug Administration issued a joint statement saying that vaccinated Americans “do not need a booster shot at this time.”  The agencies also affirmed that currently approved vaccines are still effective against variants such as Delta.  The statement was issued hours after Pfizer announced it will soon seek authorization for a COVID-19 booster to provide added protection against COVID-19 variants.  New research out of Israel suggest Pfizer’s vaccine is less effective against the Delta variant, which is prompting greater interest in booster shots. CDC and FDA have vowed to continue to review new data on vaccine efficacy as it becomes available.

Biden Outlines “Door-to-Door” Vaccination Push

On July 6, President Joe Biden announced a new community-focused effort to get more Americans vaccinated though door-to-door outreach, mobile clinics, and directing  more vaccine doses to workplaces, pharmacies, and doctor’s offices.  The President’s announcement comes as parts of the country with lower vaccination rates have seen an increase in new cases due to the Delta variant.  According to the CDC, the Delta variant comprises 51% of new COVID-19 cases in the US.  Biden also announced a goal to get as many adolescents aged 12 to 18 vaccinated as soon as possible before the school year begins as well as the mobilization of new “COVID-19 Surge Response teams” to aid communities with higher numbers of unvaccinated people. 

New Study: Vaccines Prevented 279K Deaths

According to a study released on July 7 by the Commonwealth Fund, the US vaccination campaign against COVID-19 prevented about 279,000 deaths and 1.25 million hospitalizations between December 12, 2020 and July 1, 2021.  The study also found that vaccines blunted the spread of the Alpha variant in the spring, preventing nearly 4,500 deaths per day.  However, the report warned that the Delta variant will continue to pose a “special threat” to unvaccinated populations in the coming months, requiring renewed commitment to vaccinations.

FDA Limits Use of New Alzheimer’s Drug to Early-Stage Patients

On July 8, Biogen announced that the FDA had updated the labeling for its recently approved Alzheimer’s drug so that it can only be usedfor patients with mild Alzheimer’s disease.  This change in labeling comes after the drug, known as Aduhelm, attracted criticism for being approved for all patients with all stages of Alzheimer’s when its clinical trials only included people in the earliest stages of Alzheimer’s.  The decision to narrow the number of people who can be treated with the drug could address the criticism of Aduhelm’s financial impact, which has a list price of $56,000.

Fencing Around Capitol to Come Down Soon

According to a memo from the House Sergeant at Arms to all members of Congress and staff, the remaining fencing surrounding the US Capitol Building will start being removed as early as July 9.  The black perimeter fencing was initially put up to bolster security at the Capitol in the wake of the January 6 riot.  The memo states that the Architect of the Capitol has the ability to “expeditiously reinstall” the fencing, if it is needed.  An outer perimeter fence that closed off several blocks around the Capitol was already removed in March.  Despite pending removal of the remaining fence, which is expected to take about three days, the Capitol still remains closed to visitors. 

ICYMI: New Book Looks at the Role of Presidents’ Friends

A new book by journalist and former political operative Gary Ginsburg was published on July 6, tells the story of nine friends to  US presidents and the impact of their relationships.  For example, Eddie Johnson, a longtime Jewish friend of President Harry Truman, may have played a pivotal role in lobbying the 33rd president to make the US the first nation to recognize the statehood of Israel.  Other friendships profiled include President Franklin Pierce and Nathaniel Hawthorne, author of The Scarlet Letter, and President Bill Clinton and Vernon Jones, his golfing partner.

Everything You Need to Know about COVID-19 Booster Shots

Every year, you get your flu shot.  Will the same be said for COVID-19 shots?  No one knows for sure, but federal officials and public health experts are weighing in on whether certain people might need COVID-19 booster shots as soon as this fall.  With questions about the longevity of vaccine-induced immunity and the potential for vaccine-eluding variants still unanswered, it certainly does not hurt to prepare.

What Is the Administration Planning?

On May 11, David Kessler, MD, Chief Science Officer of the White House COVID-19 Response Team, told a Senate panel that the Biden Administration is preparing for the possibility of booster shots for people who do not have a robust or long-lasting immunity, or if new variants evade protection from previously-administered vaccines.  Kessler said the booster shots would likely be a third shot of Pfizer or Modern’s mRNA vaccine rather than a new shot tailored to emerging variants.  He also confirmed that the booster shots would be free to Americans and funded by congressional appropriations through the end of Fiscal Year (FY) 2021.  Since Kessler’s testimony, the Administration purchased 200 million additional doses of Moderna’s COVID-19 vaccine in June to vaccinate children or to serve as a booster shot for adults.  Any decision to use booster shots would be up to the Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC).

Kessler’s testimony was not the first time someone raised the possibility that people vaccinated against COVID-19 could need booster shots in the future.  In February, Johnson & Johnson CEO Alex Gorsky said COVID-19 booster shots may be needed annually, like flu shots.  Similarly, Pfizer CEO Albert Bourla said in April that people will likely need a third dose of a COVID-19 vaccine within 12 months of being fully vaccinated. 

How Long Does Immunity from Vaccines Last?

Since the vaccines were just developed in 2020, experts say only time will tell how long protection from the vaccines will last.  Of the few studies conducted so far, research from the New England Journal of Medicine published in April 2021 found Moderna’s COVID-19 vaccine can produce strong antibody protection for at least six months following the second dose.  Pfizer also announced research findings in April confirming its vaccine’s efficacy six months after the second dose.  

However, new research suggests it could be for a year or longer.  A pair of studies published in May 2021 found that the B-cells of people infected with COVID-19 still continued to mature and strengthen one year after infection, suggesting some type of immune response.  More recently, a study published in the journal Nature in June suggested immunity from mRNA vaccines could last for years.

What about the Variants?

However, many of these studies were conducted before the Delta variant became more prevalent.  Public health experts say the Delta variant, which was first discovered in India in October 2020, is 43-90% more transmissible than previous COVID-19 variants, leading some to believe that currently-approved vaccine are less efficacious against the  Delta variant.  A recent study said the Delta variant could become dominant in the US by mid-July.

Fortunately, the vaccines still offer strong protection.  According to a study by Oxford University researchers, two doses of the Pfizer vaccine appears to provide 79% protection against the Delta variant, compared to 92% against the Alpha variant, which is currently the dominant variant in the US, and was first discovered in the United Kingdom in September 2020.  Since the Moderna vaccine uses the same mRNA technology as Pfizer’s, it can be inferred that two Moderna doses offer the same levels of protection as the Pfizer vaccine provides against the Delta variant. 

But what about the Johnson & Johnson vaccine?  Compared to its Moderna and Pfizer counterparts, the single-dose vaccine has been administered far less, meaning public health officials have little data regarding its effectiveness against the Delta variant.  However, experts say a Johnson & Johnson vaccine is better than no vaccine at all, and that one dose is likely effective at protecting a recipient against serious illness or death.  Additionally, former Senior Advisor to the COVID-19 Response Coordinator Andy Slavitt has said that recipients of the Johnson & Johnson could take a single mRNA booster shot now for added protection.

Nonetheless, just because the current vaccines remain effective against the Delta variant does not  mean they are  necessarily guaranteed to be effective against future variants.  As explained by CDC Director Rochelle Walensky on June 22, the Delta variant represents a “set of mutations” of COVID-19, and future mutations could produce a variant that evades protection from vaccines.  However, scientists say it’s unlikely a variant will arise that will make COVID-19 vaccines totally unless.  While vaccines appear to offer diminishing protection from being infected from newer COVID-19 variants, they still appear effective at preventing hospitalization and death.    

The Jury Is Still Out

The point of vaccines is to protect people from serious illness and death, and until fully vaccinated individuals are finding themselves with infections severe enough to require hospitalization, is it difficult to predict when booster shots will be needed and how often.  In an interview on May 21, National Institute of Allergy and Infectious Diseases Director Dr. Anthony Fauci said the need for booster shots is still unclear.  The CDC Advisory Committee on Immunization Practices reached a similar conclusion on June 24, saying there currently is not enough data to determine booster shots are needed, although the panel did not rule out the possibility of requiring booster shots if immunity wanes or new variants render existing vaccines less effective.  Considering this risk, the evolving nature of the virus, and the pain the world has already experienced at the hand of COVID-19, the US government has every reason to prepare for the worst and continue this conversation around COVID-19 booster shots.

Is an Effective Alzheimer’s Treatment Around the Corner?

More than 6.2 million Americans currently have Alzheimer’s disease, a number that is projected to double by 2050.  Despite a growing need to treat Alzheimer’s, some four decades of research have yet to yield any effective therapeutics.  This could change as soon as June 7, 2021, which is the date the Food and Drug Administration (FDA) may decide to approve a new Alzheimer’s treatment from Biogen.  Why has it been so hard to develop an effective Alzheimer’s treatment, and does Biogen’s drug mark a breakthrough?

Failed Research Efforts So Far

Since the National Institute on Aging first began studying ways to treat Alzheimer’s disease in earnest in 1978, progress on effective therapeutics has been extremely limited.  A major reason for the lack of progress is the newness of the field of neurobiology, especially as it applies to Alzheimer’s, dementia, and other complex brain disorders.  Most of the knowledge on the human brain has only been acquired within the last 40 years, while a better understanding of genetic and biologic pathways has only occurred within the last 30 years.  Additionally, brain lesions and biomarkers associated with Alzheimer’s could not be visualized until 2004.  As a result, meaningful research and development of  Alzheimer’s treatments could not accelerate until a quarter-century worth of understanding could be attained.

Since the 1990s, research pertaining to  Alzheimer’s treatments has focused on how the disease develops and progresses.  Alzheimer’s develops when toxic plaques clump together between neurons in the brain, resulting in inflammation and cell death in the brain.  Many potential drug treatments have failed while under development and at a higher rate than other drugs —  99.6% for Alzheimer’s drugs in development have failed, compared to an 80% failure rate for cancer drugs.  Among those failed potential therapies were a a pair of therapeutics from Eli Lilly and Roche, which saw their clinical trials end in February 2020.  Researchers point to the complexity of Alzheimer’s as one of the reasons why so many promising treatments have gone to the wayside.  The last Alzheimer’s therapeutic to receive FDA approval was Forest Labs’ Namenda in 2003, which along with the handful of other Alzheimer’s drugs, only alleviates symptoms temporarily

Enter Stage-Right: Aducanumab

Like other recent drug development programs, Biogen’s aducanumab is an injectable, monoclonal antibody treatment that targets plaque build-ups between neurons.  If approved, aducanumab would be the first disease-modifying drug for Alzheimer’s, meaning it is effective in slowing cognitive decline.  This could open the door to Alzheimer’s becoming a chronic disease that people live with for many years, similar to diabetes and cancer

According to data discussed during an FDA advisory committee meeting in November 2020, aducanumab proved effective in a small phase 2 clinical trial and one of two large phase 3 clinical trials. 

Will FDA Give Aducanumab the Nod?

Mr. Barker, the answer is “not sure.”  While the experimental drug was shown effective in the small phase 2 and large phase 3 trials, a second phase 3 trial failed to yield positive results.  As a result, some members of the panel have expressed a desire to see more data from an additional phase 3 trial, although such an undertaking would require another three to five years of research.  Additionally, there is some concern about the actual benefits of aducanumab, which showed only modest changes on two objective measures used in the clinical trials: the Mini-Mental State Examination and the Alzheimer’s Disease Assessment Scale. 

Also, there are concerns about side effects which may not only impact patients but also  the health care system as a whole.  30% of clinical trial participants who took the drug were found to have a reversible swelling of the brain, while over 10% had small brain bleeds.  These side effects were detected using amyloid positron emission tomography (PET) scans, and given the millions of Alzheimer’s patients, the large number of PET scans necessary to monitor for side effects would test the limits of neurologists, radiologists, and other clinicians.

What’s the Cost?

Aducanumab will be sure to have a high price tag if approved.  One year’s worth of aducanumab treatment could be priced as high as $50,000 per year, and if only a third of the 6 million Americans with Alzheimer’s were to take the drug, sales could reach $36 billion a year.  Since most people with Alzheimer’s begin noticing symptoms in their mid-60s, Medicare is likely to pick up the tab for most aducanumab treatments, not to mention the PET scans and other health care services required to monitor for side effects.

What Could Happen?

FDA is not in an enviable position on aducanumab.  The agency may determine that it cannot sign off on the safety and efficacy of the drug, or at least request more data before making a decision, despite the clear and significant need such a drug for those currently affected by Alzheimer’s and their loved ones.  As such,the projected growth in the number of Alzheimer’s patients and a lack of existing therapeutics mean any decision on June is sure to impact millions of people.