FDA VRBPAC Votes Against Recommending Approval of Booster Dose of Pfizer-BioNTech COVID-19 Vaccine

After a day of presenting booster dose data, feedback and deliberating on the efficacy of the Pfizer-BioNTech COVID-19 vaccine, the Vaccines and Related Biologic Products Advisory Committee (VRBPAC) voted 16-2 to not recommend a booster dose of the vaccine for the general population.

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.

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

During the meeting, they discussed the data related to the booster doses, breakthrough infections, and safety.

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 have been 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 to July of this year, 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.

Later two 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 said in her presentation that the country was vaccinated earlier than most others. In the summer, they saw a 10-fold increase in COVID-19 cases in 1 month.

Ron Milo, Ph.D., Professor, Weizmann Institute, Israel also presented.

Their booster data they reported showed the following:

1. 11 fold protection in people aged 18-49
2. 10 fold protection in people aged 50-59
3. 10 fold protection in people aged 65 and older

Milo 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% effective. 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 the Delta variant became the predominant strain. In addition, a retrospective study showed that vaccine effectiveness (VE) decreased primarily due to waning vaccine induced immunity rather than the 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 against the idea of a booster. More than a few were complaining over the number of participants (329), the very small amount of 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.