Pfizer Submits COVID-19 Vaccine to FDA for Emergency Authorization

Pfizer will be the first company considered for authorization of a coronavirus 2019 (COVID-19) vaccine.

The global biopharmaceutical company will submit an Emergency Use Authorization (EUA) application to the US Food and Drug Administration (FDA) today for its COVID-19 vaccine candidate BNT162b2.

The submission comes in the days following announcement from Pfizer and partnering company BioNTech that their phase 3 trial assessing the two-dose mRNA vaccine achieved all its primary efficacy endpoints without any serious adverse events thus far observed in the 43,000-plus global participants.

If authorized by the FDA, as anticipated following a public advisory committee meeting in the coming weeks, Pfizer plans to have tens of millions of doses ready for prioritized distribution and administration by the new year—and more than 1 billion doses to follow in 2021.

The Vaccine

BNT162b2 is a nucleoside-modified messenger RNA (mRNA) vaccine which encodes SARS-CoV-2 full-length spike protein glycoprotein. Of the 4 initially assessed COVID-19 vaccines from Pfizer, it was designated for greater assessment in late July, at a two-dose regimen of 30 mcg.

The mRNA platform, which is also used by biotechnology company Moderna’s COVID-19 vaccine candidate mRNA-1273, has been touted by experts including Anthony Fauci, MD, director of the National Institutes for Allergy and Infectious Diseases (NIAID), who told sister publication HCPLive® earlier this year it is responsible for the rapid development and assessment of COVID-19 vaccines these last 10 months.

The FDA granted Fast Track Designation to Pfizer and BioNTech for BNT162b2 in mid-July.

The Trial

Data shared by Pfizer and BioNTech from their four-month, phase 3 global trial showed BNT162b2 was 95% effective in preventing SARS-CoV-2 infection in treated participants regardless of prior infection, in every case measured 7 days following the second dose (P <.0001).

The trial began on July 27, and has thus far enrolled 43,661 participants, of whom 94.7% have received their second dose. Patients were randomized to either BNT162b2 or placebo at baseline.

As of this week, Pfizer reported that 42% of global participants and 30% of US participants have ethnically diverse backgrounds, and that similar rates (41% and 45%, respectively) consist of patients 56-85 years old. Their approximate 150 clinical trial sites enrolled patients from 6 countries: US, Germany, Turkey, South Africa, Brazil and Argentina.

Investigators reported the outcomes based on 170 total confirmed COVID-19 cases in the trial population—162 having been observed among placebo patients, and just 8 among patients to receive BNT162b2.

Among adults over 65 years old—a critically at-risk patient population for COVID-19 severity—the vaccine efficacy was 94%.

Just 1 of 10 observed severe COVID-19 cases in all patients occurred in the vaccinated group. Investigators stated BNT162b2 efficacy was consistent across age, gender, race, and ethnicity demographics.

Two weeks prior, Pfizer submitted data to the independent Data Monitoring Committee for their assessment of serious safety concerns associated with the vaccine. Currently, no such concerns have been reported.

Investigators reviewed unblinded reactogenicity data from the final phase 2/3 analyses for BNT162b2 involving 8000 random participants. Their findings indicated a generally good tolerance of the vaccine, with most reported adverse events resolving shortly after administration. Fatigue (3.8%) and headache (2.0%) were the only severe adverse events to occur in at least 2% of participants after the second dose.

In early October, the FDA released a guidance for COVID-19 vaccine developers, stating phase 3 trial data included in EUA applications should include a median patient follow-up duration of at least 2 months following their final dose, to assure a clear benefit-risk profile.

Distribution

Though the FDA must first clear BNT162b2 for regulation, distribution strategies are underway by Pfizer. It currently projects to produce 50 million vaccine doses globally by the end of this year, then up to 1.3 billion doses by the end of 2021.

They also announced on November 16 the launch of the US COVID-19 Immunization Pilot Program, which will use feedback and observations made from delivery and deployment practices in 4 initial states to adapt greater national vaccine distribution strategies.

The 4 states—Rhode Island, New Mexico, Tennessee, and Texas—provide Pfizer differing population sizes and diversity, as well as varying state immunization structures and disparities in urban-rural makeup.

The pilot program does not indicate these 4 states will receive differential treatment in vaccine distribution, nor earlier providence of vaccines.

Pfizer reached an agreement with the US Department of Health and Human Services (DHHS) to meet the US Operation Warp Speed program goal of 300 million COVID-19 vaccine doses by next year. Through the agreement, the federal government will receive 100 million BNT162b2 doses upon EUA approval, for a cost of $1.95 billion and an option to acquire another 500 million doses.

The unique properties of the mRNA vaccine and the current need for expedited distribution of doses during the greatest outbreak of new US COVID-19 cases yet pose a unique challenge to the company, experts have observed. Pfizer stated they will ship vaccines in temperature-controlled thermal packages that can maintain a temperature of -70 degrees Celsius through dry ice.

As some experts have explained to Contagion, appropriately storing and administering such vaccines could make the difference in their efficacy.

What Comes Next

With the FDA having now been provided phase 3 data and other required materials in the EUA application, they will deliberate on the clinical portfolio, properties, and necessity of BNT162b2 before granting authorization.

Pfizer anticipates a public Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting to discuss the vaccine’s data will be scheduled for December. The committee members will vote to either support FDA authorization or not—an outcome very historically tied to final FDA decisions.

Pfizer also anticipates its EUA will be specific to US populations at higher COVID-19 risk, as defined by the US Centers for Disease Control and Prevention (CDC), and supported by the promising phase 3 outcomes observed in such populations.

“We believe the priority will be front line health care workers, essential workers, immunocompromised individuals, nursing homes, and public safety officials, but ultimately it is the governments that will make this determination,” Pfizer wrote in a statement.

In a recent episode of the Vaccine Race podcast, William Schaffner, MD, professor of Preventive Medicine and Medicine at the Vanderbilt University Medical Center, explained a number of particularities surrounding BNT162b2 storage, distribution, and administration.

Namely, he depicted a scenario of state-organized, temperature-controlled tractor trailer convoys delivering first and second doses of the vaccine in successive waves to facilities including hospitals and nursing home facilities throughout the US.

“We’re going to have to do this in stages,” Schaffner said. “Logistically, this is going to be very challenging.”

On the front of strategic prioritization—toward a goal of achieved herd immunity through appropriate vaccination—Schaffner discussed how recent models suggest there is a slight advantage in reduced overall mortalities immunizing the highest-risk patient populations first.

But he maintained the priority would begin with healthcare workers, who would then help to vaccinate the general population.

“I think either essential workers or people at highest risk will be second in line,” Schaffner said. “The (CDC Advisory Committee on Immunization Practices) hasn’t quite decided which is which. Most other external groups have put an emphasis on vaccinating those at greatest risk next.”