FDA: SAID THERE WAS UNMET MEDICAL 'needs' THEIR CASE FOR THE 5 TO 12 PEDIATRIC POPULATION

Do you want to know what their committees discuss and the notes the FDA keeps?

FDA Vaccines and Related Biological Products Advisory Committee October 26, 2021 Meeting Document

Did you want to be in on how the FDA made their decisions about the unmet needs of 5-12 year olds getting the jab? Needs indeed. Need for the bottom line. or need for the protection of the childhood vaccination schedule immunity.

By 2021 was there a kid the MEDIA HADN’T described and dangerous snot factories and the equivalent to sewer rats that hadn’t gotten the vid. Well and is natural immunity any good. Apparently so. it was the basis for antigen based vaccines in the first place. you know.

You know mounting an immune response. and creating antibodies. And that trumped up mortality rate. they say it was one of 10 leading causes of death. was it tenth. what was that overall risk.

‘Among both younger and older children, males have higher death rates than females. In 2021, males ages 1–4 had a death rate of 27.0 per 100,000 compared with 22.9 deaths per 100,000 for females. Among children ages 5–14, males had a death rate of 16.4 deaths per 100,000 compared with 12.2 per 100,000 for females.’

According to chidlstats.gov only between 22-and 27 of 100k children die a year to begin with. If covid represented a whopping 10% that would be 2-3 kids in 100k and those would like have significant co-morbidities. At what point did we curate for died with and died of covid. the manipulation of words and numbers for end results is astounding. . What is the vaccine injury rate.

Here is the table of contents.

TABLE OF CONTENTS

LIST OF TABLES..............................................................................................................4

LIST OF FIGURES ............................................................................................................6

EXECUTIVE SUMMARY .................................................................................................7

1. BACKGROUND INFORMATION...............................................................................12

1.1. Proposed Indication...........................................................................................12

1.2. Product Description...........................................................................................12

1.3. Dosage and Administration................................................................................12

2. UNMET MEDICAL NEED..........................................................................................12

2.1. Unmet Medical Need for Safe and Effective Vaccines in the Pediatric

Population 5 to <12 Years of Age ........................................................................12

2.2. COVID-19 Pediatric Cases Have Recently Surged and Can Cause Severe

Illness, Death, and Long-Term Sequelae ..............................................................13

2.3. Vaccination of Children 5 to <12 Years May Play an Important Role in

Reducing Overall SARS-CoV-2 Transmission .....................................................14

2.4. COVID-19 Vaccination in the 5 to <12 Years Age Group Can Restore a Safe

and Effective Learning Environment....................................................................15

3. OVERVIEW OF CLINICAL STUDIES........................................................................16

3.1. Phase 1/2/3 Registrational Study C4591001.......................................................16

3.2. Phase 1/2/3 Pediatric Study C4591007...............................................................16

3.3. Overview of Methods for Evaluation of Safety, Immunogenicity, and

Efficacy..............................................................................................................17

3.3.1. Study C4591007 – Safety Analyses........................................................17

3.3.2. Study C4591007 – Immunogenicity Analyses........................................18

3.3.3. Study C4591007 – Efficacy Analyses.....................................................19

3.4. Study C4591007 – Phase 1 – Safety Results.......................................................20

3.4.1. Reactogenicity – Phase 1.......................................................................21

3.4.2. Adverse Events – Phase 1......................................................................24

3.4.3. Safety Conclusions – Phase 1.................................................................24

3.5. Study C4591007 – Phase 1 – Immunogenicity Results........................................24

3.5.1. SARS-CoV-2 Neutralizing Titers – Phase 1 ...........................................25

3.5.2. Immunogenicity Conclusions – Phase 1 .................................................25

3.5.3. Dose Selection from Phase 1 Data..........................................................25

3.6. Study C4591007 – Phase 2/3 – Safety Results....................................................25

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3.6.1. Reactogenicity – Phase 2/3 ....................................................................28

3.6.2. Overview of Adverse Events – Phase 2/3 ...............................................33

3.6.2.1. Adverse Events from Dose 1 to 1 Month After Dose 2 –

Phase 2/3......................................................................................33

3.6.2.2. Adverse Events from Dose 1 to Data Cutoff Date – Phase

2/3................................................................................................33

3.6.3. Analysis of Adverse Events – Phase 2/3.................................................34

3.6.3.1. Adverse Events from Dose 1 to 1 Month After Dose 2 –

Phase 2/3......................................................................................35

3.6.3.2. Adverse Events from Dose 1 to Data Cutoff Date – Phase

2/3................................................................................................36

3.6.3.3. Additional Adverse Event Analysis to 08 October 2021

Cutoff Date – Phase 2/3 ................................................................36

3.6.4. Deaths – Phase 2/3 ................................................................................37

3.6.5. Serious Adverse Events – Phase 2/3.......................................................37

3.6.6. Adverse Events Leading to Withdrawal – Phase 2/3 ...............................37

3.6.7. Other Significant Adverse Events – Phase 2/3 ........................................37

3.6.8. Other Safety Assessments – Phase 2/3....................................................40

3.6.8.1. Severe COVID-19 and MIS-C Illness – Phase 2/3..................40

3.6.8.2. Pregnancy – Phase 2/3...........................................................40

3.6.9. Safety Conclusions (Initial Enrollment Group) – Phase 2/3.....................40

3.7. Study C4591007 – Phase 2/3 – Additional Safety Expansion Group Results........42

3.7.1. Overview of Adverse Events – Phase 2/3 – Additional Safety

Expansion Group........................................................................................43

3.7.2. Analysis of Adverse Events – Phase 2/3 – Additional Safety

Expansion Group........................................................................................44

3.7.3. Safety Conclusions – Additional Safety Expansion Group – Phase

2/3.............................................................................................................47

3.8. Study C4591007 – Phase 2/3 – Immunogenicity Results.....................................48

3.8.1. Immunobridging Analysis – Phase 2/3 ...................................................50

3.8.2. SARS-CoV-2 Neutralizing Titers – Phase 2/3.........................................53

3.8.3. Immunogenicity Conclusions – Phase 2/3...............................................57

3.9. Study C4591007 – Phase 2/3 – Delta Variant Neutralization Immunogenicity

Results................................................................................................................57

3.10. Study C4591007 – Phase 2/3 – Efficacy Results...............................................58

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3.10.1. Efficacy Against Confirmed COVID-19 – Phase 2/3.............................60

3.10.2. Dose 1 All-Available Efficacy Population – Phase 2/3..........................61

3.10.3. Signs and Symptoms of COVID-19 – Phase 2/3 ...................................64

3.10.4. Efficacy Against Severe COVID-19 and MIS-C – Phase 2/3.................66

3.10.5. Efficacy Conclusions (Initial Enrollment Group) – Phase 2/3................66

4. SUPPORTIVE REAL WORLD AND POST-AUTHORIZATION DATA FROM

ADOLESCENTS .........................................................................................................67

5. POST-AUTHORIZATION SAFETY UPDATE.............................................................70

5.1. Safety Update from Adolescents 12 to 15 Years of Age......................................70

5.2. Pharmacovigilance............................................................................................70

6. BENEFIT/RISK ASSESSMENT...................................................................................71

7. APPENDIX..................................................................................................................72

8. REFERENCES.............................................................................................................75

LIST OF TABLES

Table 1. Follow-up Time After Dose 2 - Phase 2/3 - 5 to <12 Years of Age -

Safety Population ................................................................................26

Table 2. Disposition of All Randomized Participants – Phase 2/3, 5 to <12

Years..................................................................................................27

Table 3. Number (%) of Participants Reporting at Least 1 Adverse Event

From Dose 1 to 1 Month After Dose 2 – Phase 2/3 – 5 to <12 Years

of Age – Safety Population ..................................................................33

Table 4. Number (%) of Participants Reporting at Least 1 Adverse Event

From Dose 1 Through Cutoff Date (06SEP2021) – Phase 2/3 – 5 to

<12 Years of Age – Safety Population..................................................34

Table 5. Number (%) of Participants Reporting at Least 1 Adverse Event

From Dose 1 Through Cutoff Date (08OCT2021) – Safety

Expansion Group – Phase 2/3 – 5 to <12 Years of Age – Safety

Population...........................................................................................43

Table 6. Disposition of All Randomized Participants Through 1 Month After

Dose 2 – Immunobridging Subset – Phase 2/3 –5 to <12 Years of

Age and Study C4591001 Phase 2/3 – 16 Through 25 Years of Age......48

Table 7. Summary of Geometric Mean Ratios – Participants Without

Evidence of Infection up to 1 Month After Dose 2 –

Immunobridging Subset – Phase 2/3 – 5 to <12 Years of Age and

Study C4591001 Phase 2/3 – 16 Through 25 Years of Age –

Evaluable Immunogenicity Population.................................................51

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Table 8. Difference in Percentages of Participants With Seroresponse –

Participants Without Evidence of Infection up to 1 Month After

Dose 2 – Immunobridging Subset – Phase 2/3 – Comparison of 5 to

<12 Years of Age to Study C4591001 Phase 2/3 – 16 Through 25

Years of Age – Evaluable Immunogenicity Population .........................52

Table 9. Summary of Geometric Mean Titers – NT50 – Participants Without

Evidence of Infection up to 1 Month After Dose 2 –

Immunobridging Subset – Phase 2/3 – 5 to <12 Years of Age and

Study C4591001 Phase 2/3 – 16 Through 25 Years of Age –

Evaluable Immunogenicity Population.................................................54

Table 10. Summary of Geometric Mean Fold Rises From Before Vaccination

to Each Subsequent Time Point – NT50 – Participants Without

Evidence of Infection up to 1 Month After Dose 2 –

Immunobridging Subset – Phase 2/3 – 5 to <12 Years of Age and

Study C4591001 Phase 2/3 – 16 Through 25 Years of Age –

Evaluable Immunogenicity Population.................................................55

Table 11. Number (%) of Participants With Seroresponse – Participants

Without Evidence of Infection up to 1 Month After Dose 2 –

Immunobridging Subset – Phase 2/3 – 5 to <12 Years of Age and

Study C4591001 Phase 2/3 – 16 Through 25 Years of Age –

Evaluable Immunogenicity Population.................................................56

Table 12. Efficacy Populations – Phase 2/3 Initial Enrollment Group – 5 to

<12 Years of Age ................................................................................59

Table 13. Vaccine Efficacy – First COVID-19 Occurrence From 7 Days After

Dose 2 – Participants Without Evidence of Infection Prior to 7 Days

After Dose 2 – Phase 2/3 Initial Enrollment Group – 5 to <12 Years

of Age – Evaluable Efficacy Population...............................................61

Table 14. Vaccine Efficacy – First COVID-19 Occurrence After Dose 1 –

Phase 2/3 Initial Enrollment Group – 5 to <12 Years of Age – Dose

1 All-Available Efficacy Population.....................................................62

Table 15. Summary of Signs and Symptoms for First COVID-19 Occurrence

From 7 Days After Dose 2 – Participants Without Evidence of

Infection Prior to 7 Days After Dose 2 – Phase 2/3 Initial

Enrollment Group – 5 to <12 Years of Age – Evaluable Efficacy

Population...........................................................................................65

Table 16. Ratios Comparing Rates of Myocarditis Diagnosis of Vaccine

Compared with Historical Period and Unvaccinated Individuals............67

Table 17. Myocarditis Rates Per Dose by Sex and Age, Israel Ministry of

Health, Through 25 September 2021....................................................68

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LIST OF FIGURES

Figure 1. Estimated Reported Pediatric COVID-19 Weekly Rates in the US

by Age Group, Weeks Ending 07 March 2020 – 18 September 2021.....13

Figure 2. Participants Reporting Local Reactions, by Maximum Severity,

Within 7 Days After Each Dose – Phase 1 – 5 to <12 Years of Age

– Safety Population..............................................................................22

Figure 3. Participants Reporting Systemic Events, by Maximum Severity,

Within 7 Days After Each Dose – Phase 1 – 5 to <12 Years of Age

– Safety Population..............................................................................23

Figure 4. Participants Reporting Local Reactions, by Maximum Severity,

Within 7 Days After Each Dose – Phase 2/3 – 5 to <12 Years of

Age and `16 to 25 Years of Age – Safety Population.............................30

Figure 5. Participants Reporting Systemic Events, by Maximum Severity,

Within 7 Days After Dose 1 – Phase 2/3 – 5 to <12 Years of Age

and 16 to 25 Years of Age– Safety Population......................................31

Figure 6. Participants Reporting Systemic Events, by Maximum Severity,

Within 7 Days After Dose 2 – Phase 2/3 – 5 to <12 Years of Age

and 16 to 25 Years of Age– Safety Population......................................32

Figure 7. Cumulative Incidence Curves for the First COVID-19 Occurrence

After Dose 1 – Phase 2/3 Initial Enrollment Group – 5 to <12 Years

of Age – Dose 1 All-Available Efficacy Population..............................63

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Below is the EXECUTIVE SUMMARY

“The prophylactic Pfizer-BioNTech COVID-19 Vaccine (BNT162b2) has been available in the US for prevention of Coronavirus Disease 2019 (COVID-19) as a two-dose primary series in individuals ≥16 years of age since December 2020 under an Emergency Use Authorization (EUA 27034; 11 December 2020). An amendment to the EUA was submitted to the FDA on 09 April 2021 and was authorized on 10 May 2021 to support emergency use as a two-dose primary series in individuals ≥12 years of age. Emergency Use Authorization of a single booster dose in at risk individuals 1 ≥18 of age was granted on 22 September 2021.

A Biologics License Application (BLA) was approved on 23 August 2021 in the United States (US) for BNT162b2 30 µg administration as a two-dose primary series to individuals ≥16 years of age. Approximately 1.4 billion doses of BNT162b2 have been distributed globally as of 31 August 2021.

COVID-19 is a serious and potentially fatal or life-threatening infection for children. The pediatric population remains vulnerable to COVID-19, and pediatric cases have increased in the US, especially with widespread dissemination of the highly transmissible B.1.617.2 (Delta) variant. A 419% increase in COVID-19 cases among children <18 years of age was reported in the US in August and September 2021 compared to June and July 2021. Similar increases in pediatric COVID-19 cases have been documented globally. Although the mortality rate for COVID-19 in children is substantially lower than that in adults, COVID-19 was among the top 10 leading causes of death for children 5 to 14 years of age between January and May 2021 in the US.

Based on Centers for Disease Control and Prevention (CDC) data, among children 5 to <12 years of age there have been approximately 1.8 million confirmed and reported COVID-19 cases and 143 COVID-19-related deaths in the US through 14 October 2021. In this same age group, there have been 8622 COVID-19 related hospitalizations through 18 September 2021. This translates to cumulative incidence rates of approximately 6000 and 30 per 100,000 for confirmed COVID-19 cases and COVID-19-related hospitalizations, respectively, among children 5 to <12 years of age. The pediatric burden of COVID-19 likely exceeds that of seasonal influenza. Children can also suffer from post-acute sequelae after COVID-19. Through 04 October 2021, 5217 children in the US were diagnosed with Multisystem Inflammatory Syndrome (MIS-C), half of whom were children 5 to 13 years of age.

Although comorbidities, including asthma, diabetes, and obesity, among others, increase the risk of severe COVID-19 and hospitalization among children, approximately one-third of children who are hospitalized for COVID-19 do not have any underlying comorbidities.

Vaccination strategies in this group of children should not be restricted to those living with underlying comorbidities and should include the entire 5 to <12 years of age population in 1 A single booster dose may be administered IM at least 6 months after completing the primary series in individuals ≥65 years of age or 18 through 64 years of age who have been determined to have high risk of severe COVID-19 and/or serious complications of COVID-19 due to frequent institutional or occupational exposure in order to protect them from the unpredictable symptomatic, severe, or long sequelae of COVID-19 disease.

Children serve as important reservoirs of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and may become a primary driver of the pandemic in the near future, particularly given the recent dramatic increases in COVID-19 cases. Even asymptomatic children have been documented to shed virus for a mean of 2 weeks, leading to substantial risk of viral exposure among contacts. Preventing COVID-19 will provide direct health benefits to children and indirect educational and social development benefits can be anticipated based on alleviating the disruption to in-person education caused by COVID-19 outbreaks in school settings.

(LL because they are going to kill others is the implications)

Pfizer/BioNTech are seeking EUA of a 10-µg dose level of BNT162b2 for use in individuals 5 to <12 years of age as a two-dose primary series given 3 weeks apart. The 10-µg dose level was selected as optimal dose for the 5 to <12 years of age group based on the favorable reactogenicity profile and robust immunogenicity results from Phase 1 dose level finding evaluation (Study C4591007).

This Briefing Document (BD) contains the following supportive evidence to request EUA:

• Safety data from N~2250 participants (1518 vaccine recipients and 750 placebo recipients) 5 to <12 years of age with a follow-up time of at least 2 months after Dose 2

(Section 3.6)

• Supplemental safety data from an expansion group of an additional N~2250 participants 5 to <12 years of age recruited later than the initial enrollment group of N~2250; at the time of the most recent data cutoff date of 08 October 2021, this safety expansion group had a median follow-up time of 2.4 weeks after Dose 2 (Section 3.7).

• Effectiveness of the 10 µg dose in the 5 to <12 years of age group inferred based on the successful immuno bridging analysis, which compared SARS-CoV-2 neutralizing responses in a subset of participants in this age group in Study C4591007 to responses in a group of young adult participants 16 to 25 years of age in the C4591001 efficacy study (the most clinically similar subgroup of the study population in whom vaccine efficacy (VE) had been demonstrated) (Section 3.8.1).

• Supplemental immunogenicity analyses of a subset of participants 5 to <12 years of age in Study C4591007 evaluating serum neutralizing titers against the B.1.617.2 (Delta) variant of SARS-CoV-2 (Section 3.9).

• Descriptive efficacy analysis of children 5 to <12 years of age who were in the initial enrollment group of N~2250 to evaluate confirmed COVID-19 cases accrued up to a data cutoff date of 08 October 2021. This analysis was performed for individuals without prior evidence of SARS-CoV-2 infection up to 7 days after Dose 2 and for individuals with or without prior evidence of SARS-CoV-2 infection (Section 3.10).

Although not part of the BD, the EUA is supported by a comprehensive Chemistry, Manufacturing and Controls (CMC) data package for the 10-µg dose, that describes an improved drug product formulation buffer. The modified formulation improves vaccine stability and simplifies vaccine administration. In accordance with Centre for Biologics and Research (CBER) guidance, the modified formulation has been shown to be analytically comparable to the formulation currently authorized and approved for individuals ≥16 years of age. The exchange is not considered clinically significant.

Dose Selection

In the Phase 1 dose finding portion of the study conducted in 49 participants 5 to <12 years of age, safety and immunogenicity data demonstrated that a two-dose primary series of 10 µg BNT162b2 given 3 weeks apart had an acceptable safety profile and elicited robust immune responses against wild-type (reference strain) SARS-CoV-2, providing a balance of safety and immune responses preferable to those after immunization at the 20 and 30 µg dose levels.

Safety and Tolerability of BNT162b2 10 µg in Children 5 to <12 Years of Age Overall, the safety and tolerability profile of BNT162b2 10 µg, administered as a two-dose primary series given 3 weeks apart to approximately 1500 children 5 to <12 years of age who had at least 2 months of follow-up since their second dose, reflects age-appropriate events that are consistent with a pediatric general population and the known reactogenicity profile of BNT162b2.

The reactogenicity profile in children 5 to <12 years of age was typically mild to moderate, with a majority of events arising within the first 1 to 2 days after dosing and resolving shortly thereafter. The most common local reaction was injection site pain, and the most common systemic reactions included fatigue, headache, muscle pain, and chills.

The adverse event (AE) profile after vaccination in this age group mostly reflects reactogenicity, with low incidences of related or severe events. Few serious AEs (SAEs), none of which were related to vaccine, and no AEs leading to withdrawal were reported.

Review of AEs, SAEs, and AEs of clinical interest suggest no short-term safety concerns after administration of BNT162b2 10 µg. Complete analyses of AEs were conducted up to the EUA cutoff date of 06 September 2021, and additional AE analyses were conducted up to a cutoff date of 08 October 2021, presenting new reported AEs from the time of the EUA cutoff date up to 3 months of follow-up after Dose 2. These additional analyses have revealed no meaningful difference in the vaccine safety profile.

No cases of myocarditis/pericarditis were observed during the vaccination period through approximately 3 months of follow-up post-Dose 2 in the 5 to <12 years of age group in Study C4591007.

Supplemental safety expansion group data were analyzed from approximately 1500 vaccine recipients with a median follow-up time of 2.4 weeks after Dose 2. These supplemental data demonstrate an acceptable safety profile, in alignment with safety data from the initial enrollment group for a total of 3000 vaccinated participants contributing to safety data, with no cases of myocarditis/pericarditis reported to date. Taken together with the initial enrolled group, this supplemental safety expansion group provides safety data for a total of approximately 3000 vaccinated children 5 to <12 years of age demonstrating safety and tolerability of BNT162b2 in this age group.

Vaccine Effectiveness of BNT162b2 10 µg in Children 5 to <12 Years of Age FDA guidance specifies that a clinical study in participants 5 to <12 years of age must be adequately powered to demonstrate that the immune responses elicited in this age group (serum neutralization of SARS-CoV-2, as analyzed with seroresponse rates and geometric mean titers) are statistically non-inferior to those elicited by the vaccine in participants 16 to 25 years of age. The FDA-specified success criteria include demonstration of a noninferiority margin of –10% for seroresponse rates and a 1.5-fold margin for the ratio of geometric mean neutralizing titers.

In the Phase 2/3 portion of the study, immunobridging analyses using a validated SARS-CoV-2 neutralization assay were conducted in a randomly selected subset of participants (322 BNT162b2 and 163 placebo) among the initially enrolled N~2250 study participants. The results demonstrated that the two-dose primary series of BNT162b2 10 µg given to children 5 to <12 years of age elicited SARS-CoV-2 50% neutralizing titers that were non-inferior to the titers elicited by two doses of BNT162b2 30 µg in young adults 16 to 25 years of age in the C4591001 efficacy study (Section 3.8). Given the predominance of B.1.617.2 (Delta) variant, a supplemental analysis was conducted in 38 randomly selected subset of participants 5 to <12 years of age, using a non-validated plaque reduction neutralization assay. This analysis demonstrated that serum neutralizing titers at 1 month after Dose 2 against the B.1.617.2 (Delta) variant were comparable to those against the original SARS-CoV-2 wild-type strain. These results suggest that vaccine effectiveness against the wild-type strain inferred by immunobridging can also be reasonably inferred for effectiveness against the Delta variant.

Additionally, supportive descriptive VE analysis based on confirmed COVID-19 cases among the initially enrolled N~2250 study participants 5 to <12 years of age accrued up to the data cutoff date of 08 October 2021 was conducted. VE against laboratory-confirmed symptomatic COVID-19 occurring at least 7 days after Dose 2 in evaluable participants without evidence of prior SARS-CoV-2 infection was 90.7% (2-sided 95% confidence interval [CI]: 67.7%, 98.3%). There were no cases of severe COVID-19 and no cases of MIS-C reported as of the data cutoff date. It is notable that the earliest reported and confirmed COVID-19 case in this analysis was in July 2021, with most occurring in August and September 2021, therefore all confirmed cases have been reported during a time that the highly transmissible B.1.617.2 (Delta) has been the predominant SARS-CoV-2 strain in circulation in the US and globally. These data show that the two-dose primary series of BNT162b2 10 µg given to children 5 to <12 years of age confers a high degree of protective efficacy against COVID-19 during a period when the Delta variant of concern predominates in the US.”

By October of 2021 the data on death surely was better than their supposed view. And interrupt school. THEY (the pro-vaccine pro-mandate and pro-lockdown establishment is defined as they rather than the FDA in particular) DID THAT. imagine they then cared about school. Imagine they cared about the education system. Imagine instead they used unions to advocate schools weren’t safe unless kids were jabbed. Nice use of unions. Do they even like their members. Because I bet most teachers originally got in the game because they liked kids alot, and well, alive. between frightening parents, and trumping up statistics and using their own cush definition of effective and safe, well. that’s them.

This is an 82 page document the substack population might want to circulate and analyze.

Fda Advisory Committee October 26, 2021

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