Pfizer COVID Vaccine May Be Safe for Limited Approval, FDA Staff Says

Kerry Dooley Young

December 08, 2020

Pfizer's COVID-19 vaccine appears to be adequately safe and effective for a limited approval, according to the findings in a review by federal regulators released Tuesday.

The US Food and Drug Administration (FDA) posted a briefing document ahead of the December 10 Vaccines and Related Biological Products Advisory Committee meeting (VRBPAC).

New York-based Pfizer applied on November 20 for an emergency use authorization (EUA) for its vaccine, developed with BioNTech, as reported by Medscape Medical News. The companies want FDA clearance for use of the vaccine for people ages 16 and older, with a proposed regimen of two doses administered 21 days apart.

In their report, FDA staff said that data from research involving about 38,000 participants "suggest a favorable safety profile, with no specific safety concerns identified that would preclude issuance of an EUA" for Pfizer's vaccine.

The staff did note "a numerical imbalance of four cases of Bell's palsy" among people given the vaccine compared with no cases in the placebo group. The "four cases in the vaccine group do not represent a frequency above that expected in the general population," the FDA staff said.

"Otherwise, there were no notable patterns or numerical imbalances between treatment groups for specific categories of non-serious adverse events (including other neurologic, neuroinflammatory, and thrombotic events) that would suggest a causal relationship to BNT162b2 vaccine," as the Pfizer/BioNTech vaccine is called, the FDA staff wrote.

The FDA will consider the advisory committee's recommendations as it decides whether to approve the Pfizer vaccine, although the agency is not bound by them. The FDA is expected to act quickly on this application.

Threshold for Effectiveness

The data gathered so far on the vaccine also indicates it will meet the FDA's threshold for effectiveness. The efficacy of a two-dose administration of the vaccine has been pegged at 95.0%, with eight COVID-19 cases in the vaccine group and 162 COVID-19 cases in the placebo group. The FDA staff said that the 95% credible interval for the vaccine efficacy was 90.3% to 97.6%.

Earlier press releases from Pfizer had set an expectation that the vaccine would meet the FDA's target of at least 50% effectiveness. The FDA listed this target in a June guidance document, which allowed for a lower bound of the confidence interval at 30%.

Speaking as a guest on December 4 at a meeting of the National Vaccine Advisory Committee, the acting chairman of the FDA's December 10 VRBPAC meeting noted that the data on Pfizer’s vaccine appeared to have significantly surpassed the agency's targets.

"So we can expect that, unless there are surprises, that there will not be an issue in terms of efficacy, said Arnold Monto, MD, acting chairman of VRBPAC and a professor at the University of Michigan School of Public Health in Ann Arbor.

VRBPAC's task in considering the Pfizer vaccine involves balancing the need for rigorous examination given to any FDA application, while also taking into "consideration the issue of the extraordinary need because of the pandemic," Monto said.

As of December 8, more than 1.5 million deaths have been attributed globally to the pandemic, including more than 270,000 in the United States, according to the World Health Organization (WHO).

Protection From Disease?

More than a dozen COVID vaccine products have reached advanced levels of development, including ones developed in Russia and China, according to the WHO

The two leading candidates for the US market are the Pfizer/BioNTech vaccine and a similar vaccine developed by Moderna and the National Institute of Allergy and Infectious Diseases. The FDA's VRBPAC will review an EUA application for the Moderna vaccine on December 17.

Both the Moderna and Pfizer vaccines rely on a new approach, using messenger RNA to carry genetic instructions to try to make human cells produce specific proteins.

The Pfizer vaccine is supplied as a frozen (between -80°C to -60°C [-112°F to -76°F]), multidose (5-dose) vial, the FDA staff said. But Moderna has said its vaccine may remain stable at standard refrigerator temperatures of 2°C to 8°C (36° to 46°F), "the temperature of a standard home or medical refrigerator," for 30 days.

Among the companies with COVID vaccines in advanced testing is also Johnson & Johnson, which has highlighted the possibility of a single-dose regimen for its product.

Fierce competition among drug makers may pay off for patients. Physicians may need next year to spend time weighing the pros and cons of competing vaccines to prevent SARS-CoV-2 infection, a threat identified only in early 2020, Robert H. Hopkins Jr, MD, chairman of the US Department of Health and Human Services' National Vaccine Advisory Committee, told Medscape Medical News in an interview.

"Our challenge may turn out in the next nine months or so to be deciding which one is best for which group," said Hopkins, who is also a professor at the University of Arkansas for Medical Sciences in Little Rock. "And it may not be the same answer for all groups."

The rapid pace of development of COVID vaccines adds new challenges to the FDA's review. In the briefing document, the FDA staff stressed the conditional nature of an EUA approval.

Even with an EUA, a COVID vaccine would still be considered an "unapproved" product until the company that developed it successfully completes the FDA's procedures for a biologics license application (BLA).

To get a BLA, a vaccine developer will need to provide "greater assurance of safety based on larger numbers of vaccine recipients who have been followed for a longer period of time, and additional information about efficacy that addresses, among other questions, the potential for waning of protection over time," the FDA staff said.

The FDA staff also noted that an EUA approval for the Pfizer vaccine would not be "in and of itself, as grounds for immediately stopping blinded follow-up in an ongoing clinical trial or grounds for offering vaccine to all placebo recipients."

"To minimize the risk that use of an unapproved vaccine under EUA will interfere with long-term assessment of safety and efficacy in ongoing trials, it is critical to continue to gather data about the vaccine even after it is made available under EUA," the FDA staff said.

The FDA staff also urged against making assumptions about the potential effectiveness of a one-dose regimen of the Pfizer vaccine based on the available data. There has not yet been the kind of examination of a single-dose regimen to make an adequate comparison to the two-dose regimen, the FDA said.

"The efficacy observed after Dose 1 and before Dose 2, from a post-hoc analysis, cannot support a conclusion on the efficacy of a single dose of the vaccine, because the time of observation is limited by the fact that most of the participants received a second dose after three weeks," the FDA staff wrote.

There may be a hint, though, from the results observed to date that the Pfizer vaccine may help ward off severe cases of COVID-19, the FDA staff allowed. There were 10 study participants that had severe COVID-19 disease after the first dose: one who received the vaccine and nine who received placebo.

"The total number of severe cases is small, which limits the overall conclusions that can be drawn; however, the case split does suggest protection from severe COVID-19 disease," the FDA staff said.

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