FDA Review Confirms Early Protection from Pfizer-BioNTech COVID-19 Vaccine After First Dose

On December 10, the U.S. Food and Drug Administration (FDA) will convene a meeting of the Vaccines and Related Biological Products Advisory Committee (VRBPAC) to review the candidate COVID-19 vaccine BNT162b2, jointly developed by Pfizer and BioNTech. Today, the FDA published on its website the assessment by its internal scientists of the Emergency Use Authorization (EUA) application materials for BNT162b2. This constitutes a comprehensive and in-depth evaluation of the clinical trial data, following Pfizer and BioNTech’s announcement that this mRNA-based candidate COVID-19 vaccine achieved up to 95% efficacy in Phase 3 clinical trials.

FDA scientists stated that BNT162b2 demonstrated favorable protective efficacy and safety. Notably, further analysis of clinical data revealed that although the BNT162b2 vaccination regimen consists of two doses administered 21 days apart, protective efficacy began to emerge approximately 10 days after the first dose. Moreover, its protective efficacy showed high consistency across different age groups, ethnicities, and populations with varying risk factors.

Evaluation of Protective Efficacy

The efficacy of BNT162b2 in preventing symptomatic COVID-19 was 94.6%, with an efficacy of 95.0% among participants aged 16–55 years and 93.8% among those aged >55 years, demonstrating that it provides robust protection in older adults.

Moreover, BNT162b2 demonstrated highly consistent protective efficacy across various other risk subgroups. For instance, its protective efficacy reached 95.5% among participants with obesity (BMI >30), and 95.3% among participants with stable underlying comorbidities (including cancer, cardiovascular disease, chronic pulmonary disease, diabetes, and obesity).

Older adults and individuals with underlying comorbidities are the populations most likely to develop severe COVID-19 following SARS-CoV-2 infection; the performance of BNT162b2 indicates that these high-risk groups can achieve protection comparable to that in other populations.

An examination of the number of symptomatic COVID-19 cases in the vaccine and control groups reveals that although the BNT162b2 regimen consists of two doses administered 21 days apart, the cumulative incidence of COVID-19 began to diverge between the two groups approximately 10 days after the first dose. Exploratory analyses indicated that the efficacy of BNT162b2 was 52.4% during the interval between the first and second doses. However, FDA scientists noted that while these data suggest BNT162b2 provides a certain level of protection after a single dose, they do not demonstrate that a single dose confers long-term protection.

▲ Cumulative rate of symptomatic COVID-19 cases in the vaccine group (blue line) and the control group (red line). A significant difference in the accumulation rate between the two groups emerged approximately 10 days after the first dose (Image source: Reference [1])

In terms of protecting against severe COVID-19, a total of four cases of severe COVID-19 occurred in the vaccine group and the control group combined, seven days after completion of the two-dose vaccination regimen. In the vaccine group, one patient with severe disease had an oxygen saturation level of 93% in ambient air, meeting the predefined criteria for severe disease. However, this patient did not require hospitalization, received no further treatment, and had no risk factors for developing severe illness.

Evaluation of Vaccine Safety

Given that the COVID-19 vaccine will be administered to millions of healthy individuals, its safety and tolerability are also major concerns for scientists. According to FDA reports, the adverse events associated with BNT162b2 were primarily injection-site reactions (occurring in 84.1% of participants), fatigue (62.9%), headache (55.1%), chills (31.9%), arthralgia (23.6%), and fever (14.2%). Systemic adverse events such as fever and fatigue occurred more frequently after the second dose of the vaccine.

The incidence of serious adverse events (SAEs) was 0.6% in the vaccine group and 0.5% in the control group. However, some SAEs were considered by investigators to be unrelated to vaccination; for example, the number of appendicitis cases was higher in the vaccine group (8 cases) than in the control group (4 cases).

The FDA report indicated that adverse events potentially associated with the vaccine included lymphadenopathy, with 64 cases reported in the vaccine group and 6 cases in the control group. Additionally, three cases of Bell’s palsy occurred in the vaccine group, while none were reported in the control group. Bell’s palsy is a facial nerve paralysis causing sudden weakness or paralysis on one side of the face; most patients recover completely within several months, regardless of treatment. FDA reviewers stated that the frequency of Bell’s palsy observed was comparable to that expected in the general population.

The FDA’s review found no evidence that this COVID-19 vaccine causes vaccine-enhanced disease. However, reviewers also noted that vaccine-enhanced disease may occur when immunity wanes, and it therefore continues to warrant evaluation in ongoing clinical trials as well as in post-approval observational studies.

The documents provided by the FDA today will serve as the basis for the advisory committee’s discussion on December 10. Will BNT162b2 gain the advisory committee’s support, marking another step toward obtaining FDA Emergency Use Authorization? Let us wait and see.

References:

[1] Vaccines and Related Biological Products Advisory Committee Meeting, December 10, 2020, FDA Briefing Document, Pfizer-BioNTech COVID-19 Vaccine. Retrieved December 8, 2020, from https://www.fda.gov/media/144245/download

[2] FDA scientists endorse ‘highly effective’ Pfizer/BioNTech Covid-19 vaccine ahead of key panel. Retrieved December 8, 2020, from https://www.statnews.com/2020/12/08/fda-scientists-endorse-highly-effective-pfizer-biontech-covid-19-vaccine-ahead-of-key-panel/

[3] Pfizer’s Vaccine Offers Strong Protection After First Dose. Retrieved December 8, 2020, from https://www.nytimes.com/2020/12/08/health/covid-vaccine-pfizer.html?action=click&module=Spotlight&pgtype=Homepage

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