FDA Panel Advises Against Pfizer-BioNTech COVID-19 Booster Dose

Following lengthy testimony, the Vaccines and Related Biological Products Advisory Committee has voted against the recommendations of the Pfizer-BioNTech COVID-19 vaccine booster dose by a count of 16-2.

The committee was asked to make a decision looking at the clinical trial C4591001, which compromised 329 participants, and determining if the safety and effectiveness of the data would support approval.

The booster dose represents a single shot of the 0.3 mL approximately 6 months after the second dose in individuals 16 years and older.

After deciding to vote against recommending the approval of a booster dose for people 16 years and older, the VRBPAC decided to create a new question to vote on an Emergency Use Authorization (EUA) for a booster dose for people 65 years and older and those deemed high risk of COVID-19.

The question posed to the committee was:

Based on the totality of scientific evidence available including the safety and effectiveness data from clinical trial C4591001 do the known and potential benefits outweigh the known and potential risks of a Pfizer-BioNTech COVID-19 Vaccine booster administered at least 6 months after completion of the primary series for use in:

• Individuals 65 years and older, and
• Individuals at high risk of severe COVID-19

Committee members voiced their concerns about the lack of data to feel comfortable with having such a large amount of the American population eligible for the booster dose.

After the second vote, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Research and Evaluation, asked the committee for their opinion on health care workers and the booster dose.

They decided to pose a poll question to the committee about this group. The specific question was: should healthcare workers or others at high risk for occupational exposure be included in this EUA?

The committee voted 18-0 in favor of including healthcare workers.

The earlier meeting mainly centered on the effectiveness of the vaccine after several months and whether or not the booster is necessary to combat the Delta variant.

Sarah Oliver, MD, MSPH, Centers for Disease Control and Prevention Division of Viral Disease, National Center for Immunization and Respiratory Diseases, discussed vaccine rates, hospitalizations, and vaccine effectiveness.

To date, 380 million total vaccine doses administered, and the breakout in terms of the percentage of the population fully vaccinated for ages is the following:

• Ages ≥ 12 is 63.1%
• Ages ≥ 18 is 65.0%
• Ages ≥ 65 is 82.5%

From January-July 2021, COVID-19 hospitalization rates were 23 times higher in the unvaccinated in the 18-49 age group; 22 times higher in the unvaccinated in the 50-64 age group; and 13 times higher in the unvaccinated in those aged 65 years and older.

The vaccines’ effectiveness dropped considerable from the plus 90% range prior to the emergence of the Delta variant to dropping several percentage points after that strain became the predominant variant.

During the meeting, 2 Israeli investigators presented data regarding how that country dealt with an increase of COVID-19 and their booster strategy in order to try to stop it.

Sharon Alroy Preis, MD, MPH, MBA, director of Public Health Services, Ministry of Health, Israel during her presentation said Israel was vaccinated earlier than most other countries and up to 3 months before.

In the summer they saw a 10 fold increase in 1 month.

Their booster data they reported showed the following:

1. 11 fold protection in people aged 50-59
2. 10 fold protection in people aged 50-59
3. 10 fold protection in people aged 40-49

Ron Milo, PhD, Professor, Weizmann Institute, Israel, said there was “significant protection” with booster doses.

He explained that if VE after waning is 50 for infection and increases 10-fold it become 95%. If VE after waning is 80 for infection and increases 10-fold it becomes greater than 97%.

When asked about follow-up booster doses, Preis said it was too early to determine if people will need to be vaccinated every 6 months.

William C. Gruber, MD, senior vice president, Vaccine Clinical Research and Development Pfizer, presented for the company and said that immunity waned 6-8 months after the second dose when Delta variant is the predominant strain. In addition, a retrospective study showed that vaccine effectiveness (VE) decreased primarily due to waning vaccine induced immunity rather than due to Delta escaping vaccine protection.

Joohee Lee, MD, from the FDA, said the breakthrough infections happened more frequently to those who were vaccinated earlier than later. During her presentation Lee noted that immunogenicity data to support the effectiveness of the booster dose against the Delta variant are limited to exploratory analysis in a small number of participants using non-validated assays.

In the afternoon session during the public hearing people making presentations were mostly skeptical against the idea of a booster. More than a few were complaining over the size of the number of participants (329), the very small amount people who were 65 and older (12 participants), and the limitations on the Pfizer and Israel data.

After the public comment, there was a question and answer period and a discussion amongst the committee members. Paul Offit, MD, commented that he might be reluctant to vote yes for everyone 16 years or older, but would be open to voting for those 65 years and older.

As the committee was deliberating over the data and had their questions answered, some members seemed more inclined to want more data and that the current evidence did not confirm the need for a booster dose.

This discussion led to the vote and the aforementioned result.