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BNT162b2
2.5 Clinical Overview
CONFIDENTIAL
Page 12.5 CLINICAL OVERVIE W
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Page 2TABLE OF CONTENTS
LIST OF IN -TEXT TABL ES................................ ................................ ................................ ....5
LIST OF IN -TEXT FIGU RES................................ ................................ ................................ ...9
ABBREVIAT IONS ................................ ................................ ................................ ................. 10
2.5. CLINI CAL OVERVI EW................................ ................................ ................................ ..12
2.5.1. Product Development Rationale ................................ ................................ ........... 14
2.5.1.1. Therapeutic Context ................................ ................................ ................. 14
2.5.1.1.1. Disease or Condition ................................ .............................. 14
2.5.1.1.2. Clinical Features and Epidemiology of COVID -19............... 14
2.5.1.2. Vaccine Clinical Development Program ................................ ................. 15
2.5.1.2.1. Rationale for Development ................................ .................... 15
2.5.1.2.2. Vaccine Product I nformation ................................ ................. 15
2.5.1.2.3. Vaccine Development Program ................................ .............. 15
2.5.1.2.4. Proposed Indication ................................ ................................ 17
2.5.1.2.5. Rationale for Candidate and Dose Selection .......................... 17
2.5.1.3. Regulatory Status ................................ ................................ ..................... 18
2.5.1.4. Ethical Considerations ................................ ................................ ............. 20
2.5.2. Overview of Biopharmaceutics ................................ ................................ ............ 20
2.5.2.1. Formulation Development ................................ ................................ .......20
2.5.2.2. Biopharmaceutical Studies ................................ ................................ ......20
2.5.2.3. Bioanal ytical and Analy tical Methods Used in Human Studies .............. 20
2.5.3. Overview of Clinical Pharmacology ................................ ................................ ....21
2.5.4. Overview of Efficacy (Including Immunogenicity )................................ ............. 21
2.5.4.1. Efficacy Endpoints and Anal ysis Methods ................................ .............. 21
2.5.4.1.1. Efficacy Endpoints ................................ ................................ .21
2.5.4.1.2. Efficacy Anal ysis Methods ................................ .................... 23
2.5.4.2. I mmunogenicit y Endpoints and Analy sis Methods ................................ .23
2.5.4.2.1. I mmunogenicity Endpoints ................................ .................... 23
2.5.4.2.2. I mmunogenicity Analy sis Methods ................................ .......23
2.5.4.3. Efficacy Results ................................ ................................ ....................... 24
2.5.4.3.1. Updated Anal ysis of Efficacy –Adolescents 12 -15
Years of Age ................................ ................................ ...................... 24
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Page 32.5.4.4. I mmunogenicit y Results ................................ ................................ .......... 36
2.5.4.4.1. I mmunogenicity Populations ................................ .................. 36
2.5.4.4.2. Noninferiorit y Between 12- 15 Years of Age and 16 -25
Years of Age Groups ................................ ................................ ......... 37
2.5.4.4.3. I mmunogenicity Conclusions ................................ ................. 37
2.5.5. Overview of Safety................................ ................................ ............................... 38
2.5.5.1. Safet y Endpoints and Anal ysis Methods ................................ ................. 38
2.5.5.1.1. Safet y Endpoints ................................ ................................ ....38
2.5.5.1.2. Safet y Anal ysis Methods ................................ ........................ 39
2.5.5.2. Safet y Results ................................ ................................ .......................... 40
2.5.5.2.1. Safet y Populations ................................ ................................ ..40
2.5.5.2.2. Reactogenicit y................................ ................................ ........ 47
2.5.5.2. 3. Adverse Events ................................ ................................ .......47
2.5.5.2.4. Deaths ................................ ................................ ..................... 98
2.5.5.2.5. Serious Adverse Events ................................ .......................... 98
2.5.5.2.6. Adverse Events L eading to Withdrawal ............................... 111
2.5.5.2.7. Other Significant Adverse Events –Phase 3 ........................ 112
2.5.5.3. Other Safet y Assessments ................................ ................................ ......119
2.5.5.3.1. Severe COVID -19 Illness ................................ ..................... 119
2.5.5.3.2. Pregnancies ................................ ................................ ........... 120
2.5.5.3.3. Adverse Drug Reactions................................ ....................... 120
2.5.5.4. Safet y in Special Groups and Situations ................................ ................ 120
2.5.5.4.1. Geriatric Use ................................ ................................ ........ 120
2.5.5.4.2. Pediatric Use ................................ ................................ ........ 120
2.5.5.4.3. Use During Pregnancy and Lactation................................ ...120
2.5.5.4.4. Use in Immunocompromised Individuals ............................ 121
2.5.5.4.5. Other Safet y Considerations ................................ ................. 121
2.5.5.5. Post -Auth orization Safety Summary ................................ ..................... 121
2.5.5.6. Safet y Conclusions ................................ ................................ ................ 122
2.5.6. Benefits and Risks Conclusions ................................ ................................ ......... 122
2.5.6.1. Benefits ................................ ................................ ................................ ..123
2.5.6.2. Risks ................................ ................................ ................................ ......123
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Page 42.5.6.3. Supportive Real World and Post -Authorization Data Following
Use of BNT162b2 in Children 12 -15 Years of Age ................................ ......125
2.5.6.4. Benefit -Risk Conclusions ................................ ................................ ......126
2.5.7. References ................................ ................................ ................................ .......... 128
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Page 5LIST OF IN -TEXT TABL ES
Table 1. Efficacy Populations –Subjects 12 Through 15 Years of Age –
Blinded Placebo -Controlled Follow- up Period ................................ ........ 26
Table 2. Vaccine Efficac y –First COVID -19 Occurrence From 7 Day s After
Dose 2 –Blinded Placebo-Controlled Follow- up Period –Subjects
12 Through 15 Years of Age and Without Evidence of Infection
Prior to 7 Day s After Dose 2 – Evaluable Efficacy (7 Day s)
Population ................................ ................................ ................................ .28
Table 3. Vaccine Efficacy –First COVID -19 Occurrence From 7 Day s After
Dose 2 –Blinded Placebo-Controlled Follow- up Period –Subjects
12 Through 15 Years of Age and With or Without Evidence of
Infection Prior to 7 Day s After Dose 2 –Evaluable Efficacy (7
Days) Population ................................ ................................ ...................... 29
Table 4. Vaccine Efficacy –First COVID -19 Occurrence After Dose 1 –
Blinded Placebo -Controlled Follow- up Period – Subjects 12
Through 15 Years of Age –Dose 1 All -Available Efficacy
Population ................................ ................................ ................................ .31
Table 5. Summary of SARS -CoV -2 Variants for the First COVID -19
Occurrence From 7 Day s After Dose 2 –Blinded Placebo -
Controlled Follow- up Period –Subjects 12 Through 15 Years of
Age and With or Without Evidence of Infection Prior to 7 Day s
After Dose 2 – Evaluable Efficacy (7 Day s) Population .......................... 34
Table 6. Summary of SARS -CoV -2 Variants of Concern or Variants of
Interest for the First COVID -19 Occurrence From 7 Day s After
Dose 2 –Blinded Placebo-Controlled Follow- up Period –Subjects
12 Through 15 Years of Age and With or Without Evidence of
Infection Prior to 7 Day s After Dose 2 – Evaluable Efficacy (7
Days) Population ................................ ................................ ...................... 35
Table 7. Safety Population – Phase 2/3 Subjects 12 Through 15 Years of
Age................................ ................................ ................................ ............ 40
Table 8. Follow -up Time After Dose 2 – Phase 2/3 Subjects 12 Through 15
Years of Age –Safet y Population ................................ ............................ 41
Table 9. Follow -up Time After Dose 1 of BNT162b2 – Phase 2/3 Subjects
12 Through 15 Years of Age (Subjects Who Originally Received
Placebo) – Safety Popul ation ................................ ................................ ....42
Table 10. Disposition of All Randomized Subjects – Phase 2/3 Subjects 12
Through 15 Years of Age ................................ ................................ ......... 43
Table 11. Demographic Characteristics –Phase 2/3 Subjects 12 Through 15
Years of Age –Safet y Population ................................ ............................ 46
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Page 6Table 12. Incidence Rates of at Least 1 Adverse Event From Dose 1 to
Unblinding Date –Blinded Placebo -Controlled Follow -up Period –
Phase 2/3 Subjects 12 Throu gh 15 Years of Age – Safety
Population ................................ ................................ ................................ .50
Table 13. Incidence Rates of at Least 1 Adverse Event From Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term –
Blinded Placebo -Controlled Follow- up Period – Phase 2/3 Subjects
12 Through 15 Years of Age –Safet y Population ................................ ....53
Table 14. Number (%) of Subjects Reporting at Least 1 New Adverse Event
After the EUA Snapshot, From Dose 1 to Unblinding Date –
Blinded Placebo -Controlled Follow- up Period – Phase 2/3 Subjects
12 Through 15 Years of Age –Safet y Popu lation ................................ ....61
Table 15. Number (%) of Subjects Reporting at Least 1 New Adverse Event
After the EUA Snapshot, From Dose 1 to Unblinding Date, by
System Organ Class and Preferred Term –Blinded Placebo -
Controlled Follow- up Period –Phase 2/3 Subjects 12 Through 15
Years of Age –Safet y Population ................................ ............................ 62
Table 16. Number (%) of Subjects Reporting at Least 1 New Severe Adverse
Event After the EUA Snapshot, From Dose 1 to Unblinding Date,
by System Organ Class and Preferred Term –Blinded Placebo -
Controlled Follow- up Period –Phase 2/3 Subjects 12 Through 15
Years of Age –Safet y Population ................................ ............................ 66
Table 17. Incidence Rates of at Least 1 Adverse Event From Unbli nding Date
to Data Cutoff Date (02SEP2021) –Open -Label Follow -up Period
–Subjects Who Originally Received BNT162b2 –Phase 2/3
Subjects 12 Through 15 Years of Age –Safet y Population ..................... 68
Table 18. Number (%) of Subjects Reporting at Least 1 Adverse Event From
Dose 1 to 6 Months After Dose 2 –Subjects With at Least 6
Months of Follow- up Time After Dose 2 – Phase 2/3 Subjects 12
Throug h 15 Years of Age (Subjects Who Originally Received
BNT162b2) –Safet y Population ................................ .............................. 71
Table 19. Number (%) of Subjects Reporting at Least 1 Adverse Event From
Dose 1 to 6 Months After Dose 2, b y Time Period – Subjects With
at Least 6 Months of Follow- up Time After Dose 2 – Phase 2/3
Subjects 12 Through 15 Years of Age (Subjects Who Originally
Received BNT162b2) –Safety Population ................................ ............... 72
Table 20. Number (%) of Subjects Reporting at Least 1 Adverse Event From
Dose 1 to 6 Months After Dose 2, b y System Organ Class and
Preferred Term – Subjects With at Least 6 Months of Follow -up
Time After Dose 2 – Phase 2/3 Subjects 12 Through 15 Years of
Age (Subjects Who Originally Received BNT162b2) –Safet y
Population ................................ ................................ ................................ .74
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Page 7Table 21. Number (%) of Subjects Reporting at Least 1 Adverse Event From
Dose 1 to 6 Months After Dose 2, b y System Organ Class and
Preferred Term and Time Period – Subjects With at L east 6 Months
of Follow -up Time After Dose 2 – Phase 2/3 Subjects 12 Through
15 Years of Age (Subjects Who Originally Received BNT162b2) –
Safety Population ................................ ................................ ...................... 78
Table 22. Number (%) of Subjects Reporting at Least 1 New Adverse Event
After the EUA Snapshot, From Dose 1 to 6 Months After Dose 2 –
Subjects With at Least 6 Months of Follow -up Time After Dose 2 –
Phase 2/3 Subjects 12 Through 15 Years of Age (Subjects Who
Originall y Received BNT162b2) – Safet y Population ............................. 82
Table 23. Number (%) of Subjects Reporting at Least 1 New Adverse Event
After the EUA Snapshot, From Dose 1 to 6 Months After Dose 2,
by Time Period – Subjects With at Least 6 Months of Follow -up
Time After Dose 2 – Phase 2/3 Subjects 12 Through 15 Years of
Age (Subjects Who Originally Received BNT162b2) –Safet y
Population ................................ ................................ ................................ .84
Table 24. Number (%) of Subjects Reporting at Least 1 New Adverse Event
After the EUA Snapshot, From Dose 1 to 6 Month s After Dose 2,
by System Organ Class and Preferred Term –Subjects With at
Least 6 Months of Follow -up Time After Dose 2 –Phase 2/3
Subjects 12 Through 15 Years of Age (Subjects Who Originally
Received BNT162b2) –Safety Population ................................ ............... 85
Table 25. Number (%) of Subjects Reporting at Least 1 New Adverse Event
After the EUA Snapshot, From Dose 1 to 6 Months After Dose 2,
by System Organ Cl ass and Preferred Term and Time Period –
Subjects With at Least 6 Months of Follow -up Time After Dose 2 –
Phase 2/3 Subjects 12 Through 15 Years of Age (Subjects Who
Originall y Received BNT162b2) – Safet y Population ............................. 88
Table 26. Incidence Rates of at Least 1 Adverse Event From Dose 3 to Data
Cutoff Date (02SEP2021) – Open -Label Follow -up Period –
Subjects Who Originally Received Placebo and Then Received
BNT162b2 After Unblinding –Phase 2/3 Subjects 12 Through 15
Years of Age –Safet y Population ................................ ............................ 92
Table 27. Incidence Rates of at Least 1 Adverse Event From Dose 3 to Data
Cutoff Date (02SEP2021), by System Organ Class and Preferred
Term –Open -Label Follow -up Period – Subjects Who Originally
Received Placebo and Then Received BNT162b2 After Unblinding
–Phase 2/3 Subjects 12 Through 15 Years of Age – Safet y
Population ................................ ................................ ................................ .93
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Page 8Table 28. Incidence Rates of at Least 1 Serious Adverse Event From Dos e 1
to Unblinding Date, b y System Organ Class and Preferred Term –
Blinded Placebo -Controlled Follow- up Period – Phase 2/3 Subjects
12 Through 15 Years of Age –Safet y Population ................................ ..101
Table 29. Number (%) of Subjects Reporting at Least 1 New Serious Adverse
Event After the EUA Snapshot, From Dose 1 to Unblinding Date,
by System Organ Class and Preferred Term –Blinded Placebo -
Controlled Follow -up Period –Phase 2/3 Subjects 12 Through 15
Years of Age –Safet y Population ................................ .......................... 103
Table 30. Number (%) of Subjects Reporting at Least 1 Serious Adverse
Event From Dose 1 to 6 Months After Dose 2, b y System Organ
Class and Preferred Term –Subjects With at L east 6 Months of
Follow -up Time After Dose 2 – Phase 2/3 Subjects 12 Through 15
Years of Age (Subjects Who Originally Receiv ed BNT162b2) –
Safety Population ................................ ................................ .................... 105
Table 31. Number (%) of Subjects Reporting at Least 1 Serious Adverse
Event From Dose 1 to 6 Months After Dose 2, b y System Organ
Class and Preferred Term and Time Period – Subjects With at L east
6 Months of Follow- up Time After Dose 2 – Phase 2/3 Subjects 12
Through 15 Years of Age (Subjects Who Originally Received
BNT162b2) –Safet y Population ................................ ............................ 106
Table 32. Number (%) of Subjects Reporting at Least 1 New Serious Adverse
Event After the EUA Snapshot, From Dose 1 to 6 Months Af ter
Dose 2, b y System Organ Class and Preferred Term –Subjects
With at Least 6 Months of Follow -up Time After Dose 2 – Phase
2/3 Subjects 12 Through 15 Years of Age (Subjects Who Originally
Received BNT162b2) –Safety Population ................................ ............. 108
Table 33. Number (%) of Subjects Reporting at Least 1 New Serious Adverse
Event After the EUA Snapshot, From Dose 1 to 6 Months After
Dose 2, b y System Or gan Class and Preferred Term and Time
Period – Subjects With at Least 6 Months of Follow -up Time After
Dose 2 –Phase 2/3 Subjects 12 Through 15 Years of Age (Subjects
Who Originally Received BNT162b2) –Safet y Population .................. 109
Table 34. Incidence Rates of at Least 1 Serious Adverse Event From Dose 3
to Data Cutoff Date (02SEP2021), by System Organ Class and
Preferred Term –Open -Label F ollow -up Period –Subjects Who
Originall y Received Placebo and Then Received BNT162b2 After
Unblinding –Phase 2/3 Subjects 12 Through 15 Years of Age –
Safety Population ................................ ................................ .................... 111
Table 35. Subjects Reporting an Adverse Event of Lymphadenopath y –
Blinded Placebo -Controlled Follow- up Period – Phase 2/3 Subjects
12 Through 15 Years of Age –Safet y Population ................................ ..114
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Page 9Table 36. Incidence Rates of at Least 1 Adverse Event of Special Interest
From Dose 1 to Unblinding Date, b y System Organ Class and
Preferred Term –Blinded Pla cebo -Controlled Follow -up Period –
Phase 2/3 Subjects 12 Through 15 Years of Age –Safety
Population ................................ ................................ ............................... 116
Table 37. Subjects Reporting an Adverse Event of Arthralgia – Blinded
Placebo- Controlled Follow -up Period – Phase 2/3 Subjects 12
Through 15 Years of Age –Safet y Population ................................ .......118
Table 38. Number (%) of Subjects Reporting at Least 1 New Adverse Event
of Special Interest After the EUA Snapshot, From Dose 1 to
Unblinding Date, b y System Organ Class and Preferred Term –
Blinded Placebo -Controlled Follow- up Period – P hase 2/3 Subjects
12 Through 15 Years of Age –Safet y Population ................................ ..119
LIST OF IN -TEXT FIGU RES
Figure 1. Cumulative I ncidence Curves for the First COVID- 19 Occurrence
After Dose 1 – Subjects 12 Through 15 Years of Age –Blinded
Placebo- Controlled Follow -up Period – Dose 1 All -Available
Efficacy Population ................................ ................................ .................. 32
Figure 2. Phase 2/3 Safet y Anal yses of Adolescent Participants: Time Periods
and Anal ysis Groups ................................ ................................ ................. 49
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Page 10ABBREVIATIONS
Abbreviation Definition
ACIP Advisory Committee on Immunization Practices
ADR adverse reaction
AE adverse event
AESI adverse event of special interest
BLA (US FDA) Biologics License Application
BMI body mass index
CBER (US FDA) Center for Biologics Evaluation and Research
CDC (US) Centers for Disease Control and Prevention
CFR case fatality rate
CI confidence interval
CO Clinical Overview
COVID -19 Coronavirus Disease 2019
CSR Clinical Study Report
DART developmental and reproductive toxicity
ECMO extracorporeal membrane oxygenation
EKG electrocardiogram
EMA European Medicines Agency
ER emergency room
EU European Union
EUA Emergency Use Application
FDA (US) Food and Drug Administration
FIH first-in-human
GCP Good Clinical Practice
GLP Good Laboratory Practice
GMFR geometric mean -fold rise
GMR geometric mean ratio
GMT/GMC geometric mean titer/concentration
HIV human immunodeficiency virus
ICH International Council on Harmonisation
ICU intensive care unit
IM intramuscular(ly)
IND Investigational New Drug application
iPSP initial Pediatric Study Plan
IQR interquartile range
IR incidence rate
LNP lipid nanoparticle
MAA Marketing Authorisation Application
MedDRA Medical Dictionary for Regulatory Activities
modRNA nucleoside- modified messenger RNA
mRNA messenger RNA
NAAT nucleic acid amplification testing
NHP non-human primate
NI noninferiority
PDCO Paediatric Committee
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Page 11Abbreviation Definition
PCR polymerase chain reaction
PIP Paediatric Investigational Plan
PSP Pediatric Study Plan
PT Preferred Term
PY person -years
RNA ribonucleic acid
RNA -LNP RNA lipid nanoparticle
RT-PCR reverse transcription –polymerase chain reaction
SAE serious adverse event
SAP statistical analysis plan
SARS severe acute respiratory syndrome
SARS -CoV-2 SARS Coronavirus -2; virus causing the disease COVID -19
SMQ Standard ized MedDRA query
SOC System Organ Class
TME targeted medical event
US United States
VAERS Vaccine Adverse Event Reporting System
VE vaccine efficacy
VOC Variant of Concern
VOI Variant of Interest
WHO World Health Organization
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Page 122.5. CLINICAL OVERVIEW
This Clinical Overview (CO) describes the clinical data for a prophy lactic, RNA -based
SARS -CoV -2 vaccine developed b y BioNTech and Pfizer. Evidence is summarized in this CO
for the updated efficacy and safet y and tolerability of the vaccine administered to health y
adolescent participants 12 -15 years of age .Additional safet y and efficacy details are presented in
Module 5.3.5.1 C4591001 Adolescent 6- Month Update Interim CSR .
The pivotal data are derived from a single registration alstudy , Phase 1/2/3 Study C4591001,
conducted under a United States (US) Investigational New Drug ( IND) Applica tion. The
clinical experience reflected in this CO represents 2260study participants 12-15 years of age .
The proposed indication and dosing administration for BNT162 b2(30 µg) are:
Proposed i ndication : Active immunization to prevent COVI D-19 disease caused by
SARS -CoV -2 virus ,in individuals ≥12yearsof age
Dosing administration :single 0.3 mL intramuscular (IM) dose followed by a second 0.3mL
dose 3 weeks later
Study C4591001, an ongoing Phase 1/2/3 study ,is the registrational and pivotal study of the
prophy lactic BNT162b2 vaccine candidate against COVID -19 in healthy individuals
≥12years of age that was initiated in April 2020.
This ongoing study has demonstrated the safet y, tolerability , immunogenicity , and efficacy of
BNT162b2 when administered as 2 doses of 30 µg given approximately 21 day s apart, which
was the basis of the current authorizations and approvals. Study C4591001 data supporting
authorization or licensure for the 2 -dose series in particip ants ≥12 y ears of age are
summarized below:
Phase 1 evaluated safet y and immunogenicit y results in healthy adult participants
across dose levels of 2 vaccine candidates, BNT162b1 and BNT162b2. The Phase 1
reactogenicity and immunogenicity profiles, combine d with available nonclinical
animal study data, led to the selection of BNT162b2 at the 30 -µg dose level to
advance to Phase 2/3 evaluation.
Phase 2/3 evaluated efficacy of BNT162b2 30 µg, and provided additional safet y,
efficacy , and immunogenicity data i n a larger population. Prespecified efficacy (event
driven) in participants ≥12 y ears of age and ongoing safet y data in participants
≥16years of age with a median of at least 2 months of follow -up after Dose 2 and up
to a data cutoff date of 14 November 2 020 were previously reported in the C4591001
Final Anal ysis Interim Clinical Study Report ( CSR) , dated 03 December 2020
(Module 5.3.5.1 C4591001 Final Anal ysis Interim CSR ). On 11 December 2020, the
US FDA issued an EUA for use of BNT162b2 at 30 µg in indi viduals ≥16 y ears of
age.
For adolescents (12 through 15 years of age), immunobridging and safet y (median
≥2months follow -up) were compared with young adults 16 through 25 years of age
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Page 13were reported in the adolescent interim CSR, dated 14 April 2021 (Module 5.3.5.1
C4591001 Adolescent Interim CSR ). Immunogenicity data from adolescent (and
young adult) participants showed robust neutralizing GMTs after vaccination with 2
doses of BNT162b2 at 30 µg. In addition, descriptive efficacy analy ses during
blinded p lacebo -controlled follow -up period conducted on all confirmed COVID-19
cases accrued up to the data cutoff date of 13 March 2021 for adolescents (12 through
15 years of age) showed estimated vaccine efficacy (VE)was 100.0% for cases
reported from at least 7days after Dose 2 in individuals without and with or without
evidence of prior SARS -CoV -2 infection before and during vaccination regimen. On
10May 2021, the US FDA issued an EUA for use in individuals 12 to 15 y ears of
age. At present, there are curre ntly no licensed vaccines in the US to immunize
against COVID -19 for individuals 12 to 15 y ears of age.
Follow -up to 6 months after Dose 2 was provided in the C4591001 6 -Month Update
Interim CSR, dated 29 April 2021 ( Module 5.3.5.1 C4591001 6- Month Update
Interim CSR ), and provided up to 6 months of additional safet y, efficacy, and
immunogenicit y follow- up data. The report included anal ysis of safet y during the
blinded and post -unblinding (open -label) periods through 6 months post -Dose 2 for
participants ≥16years of age, and updated efficacy anal ysis based on all confirmed
COVID -19 cases in participants ≥12 years of age that accrued in blinded follow -up to
a data cutoff date of 13 March 2021. On 23 August 2021, the US FDA granted
licensure of COMIRNATY (BNT 162b2) for individuals ≥16 y ears of age.
Based on a data cutoff date of 02 September 2021, this CO for adolescent participants 12
--15 years of age summarizes updated descriptive efficacy anal yses from 7 days after Dose 2
during blinded placebo -controlled follow -up (Section 2.5.4.3.1 ) and the following safet y
data, as ordered:
Blinded placebo -controlled follow -up period from Dose 1 to the date of unblinding
for BNT162b2 and placebo participants, including new AEs that were reported after
the EUA snapshot date (based on events on or after the data cutoff date of
13March 2021) ( Section 2.5.5.2.3.1 )
Open -label observational follow -up period of original BNT162b2 recipients from the
date of unblinding to the data cutoff date ( Section 2.5.5.2.3.2 )
Cumulative safety from Dose 1 to at least 6 months after Dose 2, inclusive of blinded
data and open label -data for original BNT162b2 recipients, including new AEs that
were reported after the EUA snapshot date ( Section 2.5.5.2.3.3 )
Open -label observational follow -up period for original placebo recipients who then
received BNT162b2 from the first dose of BNT162b2 to the data cutoff date
(Section 2.5.5.2.3.4 )
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Page 142.5.1. Product Development Rationale
2.5.1.1. Therapeutic Context
2.5.1.1.1. Disease or Condition
COVID -19 is caused by SARS -CoV -2, a zoonotic virus that first emerged as a human
pathogen in China and has rapidly spread around the world by human- to-human
transmission.
At the time of this submission, the ongoing pandemic remains a significant challenge to
public health and economic stability worldwide, for which for a licensed prophy lactic
vaccine is a necessary and critical mitigation across all age groups.
2.5.1.1.2. Clinical Features and Epidemiology of COVID-19
COVID -19 presentation is generall y with cough and fever, with chest ra diography showing
ground -glass opacities or patch y shadowing.1However, man y patients present without fever
or radiographic changes, and infections may be asy mptomatic which isrelevant to controlling
transmission. For sy mptomatic patients, disease progression may lead to acute respiratory
distress sy ndrome requiring ventilation , subsequent multi -organ failure , and death .1
Common sy mptoms in hospitalized pat ients (in order of highest to lowest frequency ) include
fever , dry cough, shortness of brea th,fatigue, myalgias, nausea/vomiting or diarrhea,
headache, weakness, and rhinorrhea .1Anosmia (loss of smell) or ageusia (loss of taste) may
be the sole presenting s ymptom in approximately 3%of individuals who have COVID -19.1
The US Centers for Disease Control and Prevention (CDC) defined COVID -19 sy mptoms as
including 1or more of the following :2fever , new or increased cough, new or increased
shortness of breath ,chills, new or increased muscle pain , new loss of taste or smell, sore
throat , diarrhea , vomiting , fatigue , headache , nasal congestion or runn y nose , or nausea .
All ages may present with the disease, with case fatality rates (CFR) elevated in persons
>60years of age.3Comorbidities are associated with increased CFR, including
cardiovascular disease, diabetes, hypertension, and chronic respiratory disease.4Healthcare
workers are over -represented among COVID -19 patients due to occupational exposure to
infected patients.4
With the widespread availability of COVID -19 vaccines in the United States, the disease
burden has shifted to increasingl y impact younger age gr oups, particularl y pediatric and
adolescent populations who remain largely unvaccinated.5As of the week ending October 16,
2021, the age groups 5 -11, 12 -15, and 16- 17 years had among the highest weekl y case rates
per 100,000 population (164.1, 154.0, and 163.8 per 100,000, respectivel y).6Although the
hospitalization rate among those 12 -17 years of age is low relative to other age groups
(1.6/100,000 or lower since October 2021)7, among those who are hospitalized, the risk of
progression to severe disease (requiring ICU admission, invasive mechanical ventilation, or
in-hospital death) in this age group is approximately 30-34%.8,9,10
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Page 152.5.1.2. Vaccine Clinical Development Program
2.5.1.2.1. Rationale for Development
2.5.1.2.1.1. Current Therapies
Currently available therapies have different benefit- risk considerations depending on the
stage of illness and disease manifestations.1,11Monoclonal antibody therapies help prevent
hospitalizat ionandreduce viral load and severe s ymptoms.12While care for individuals who
have COVID -19 has improved with clinical experience, vaccination is the most effective
medical countermeasure to decrease risk and mitigate spread of the SARS -CoV -2 virus
during the ongoing pandemic .
2.5.1.2.1.2. BNT162b2 Development
Pfizer and BioNTech develop ed an investigational vaccine that targets SARS -CoV -2,
intended toprevent COVID -19, for which BioNTech initiate da first-in-human (FIH)study in
April 2020 in German y (BNT162- 01) andPfizer initiate da Phase 1/2/3 study (C4591001)
shortly afterwards in the US which expanded to include global sites upon initiation of the
Phase 2/3 part of the study . Additional information on Study C4591001 is provided in
Section 2.5.1.2.3.2.1 .
The vaccine is based on SARS -CoV -2 spike gl ycoprotein (S)antigens encoded in RNA
formulated in lipid nanoparticles (LNPs) and is referred to as BNT162b2 (BioNTech code
number BNT162, Pfizer code number PF -07302048) .The structural elements of the vector
backbones of BNT162 vaccines are optimized for prolonged and strong translation of the
antigen -encoding RNA. The potency of RNA vaccines is further optimized by encapsula tion
of the RNA into LNPs, which protect the RNA from degradation b y RNAses and enable
transfection of host cells after IM delivery .
2.5.1.2.2. Vaccine Product Information
BioNTech has developed multiple RNA lipid nanoparticle (RNA -LNP )platforms, including
nucleoside -modified RNA (modRNA) which has blunted innate immune sensor activating
capacity and thus augmented antigen expression. The current vaccine formulation is
described in Section 2.5.2.1 .
2.5.1.2.3. Vaccine Development Program
2.5.1.2.3.1. Nonclinical Stud ies
Key nonclinical evaluation sof BNT162b2 included pharmacology (mouse immunogenicit y
studies, non-human primate [ NHP ]immunogenicity and challenge studies) and toxicity
(two Good Laboratory Practice [ GLP] rat repeat- dose toxicity studies )invitro and in vivo.
Adevelopmental and reproductive toxicity (DART )study was completed in rats.
These data supported the clinical development of BN T162b2 and were previously submitted.
Additional details of nonclinical studies were provided in Module 2.4 Nonclinical Overview .
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Page 162.5.1.2.3.2. Clinical Stud ies
2.5.1.2.3.2.1. Phase 1/2/3 Study C4591001
Study C4591001 is the ongoing, randomized, placebo -controlled, Pha se 1/2/3 registration
study . The stud y design, eligibility criteria, endpoints and anal ysis methods are detailed in
the C45910 01 Protocol and Statistical Analy sis Plan and have been described in prior
submissions.
Data from C4591001 participants in all pha ses and all age groups have been previously
submitted. All ongoing C4591001 p articipants remain in study follow -upfor up to
approximately 2 years after Dose 2 of randomized study intervention, except for those who
enrolled into Study C4591031 for a booste r evaluation.
Study Eligibility Criteria
In Phase 2/3, participants were enrolled with stratification of younger adults (18 to 55 years
of age) and older adults (>55 years of age) to achieve approximately 40% enrollment in the
older adult group. Additional adolescents were added later b y a protocol amendment: older
adolescents 16 to 17 years of age are included in the y ounger adult stratum (ie, 16 to 55 y ears
of age) , and y ounger adolescents 12 to15years of age were analyzedas a separate age
stratum. Eli gibility in Phase 2/3 included higher risk for acquiring COVID-19 in the
investigator’s judgment, due to medical conditions or exposure, such as:
Chronic condition (eg, hy pertension; diabetes; asthma; pulmonary , liver, or kidney
disease)
Autoimmune disease requiring therapeutic intervention (or history of)
Chronic HIV, HCV, or HBV infection that is stable and controlled
Vaping or smoking (or history of smoking within the prior y ear)
Resident in a long- term facility
Occupation with high risk of SARS -CoV -2 exposure (eg, healthcare, emergency
response)
Phase 3 (which is ongoing) included planned interim analy ses of the first primary efficacy
endpoint, ongoing efficacy and safet y evaluations including reactogenicity assessment in a
subset of participants, and exploratory vaccine immunogenicit y evaluation in a subset of
participants. Phase 3 is being conducted at sites in the US, Brazil, Argentina, Turkey , South
Africa, and German y. Participants were stratified by age group as previously described. The
final eff icacy anal ysis was conducted when at least the prespecified total number of
164efficacy events accrued. Safet y and long -term persistence of efficacy follow -up will
continue for at least 2 y ears and/or end of study . Safety and efficacy anal yses included the
360participants who were anal yzed for Phase 2.
Unblinding Considerations
Unblinding to randomized treatment assignment has completed for participants 12-15years
of age in the stud y, with respect to the participants, Sponsor, andsite personnel . This i s
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Page 17subsequent to authorizations/approvals granted in the US and other regions in this age group
starting in May 2021(refer to Section 2.5.1.3 ).
Individual s 12-15years of age or older have been unblinded at such time that they become
locally eligible and wish to know their treatment assignment to confirm prior vaccination
with BNT162b2 (if randomized to this group), or to receive BNT162b2 (if randomized to
placebo) . Unblinded recipients originall y randomized to BNT162b2 continue to be followed
in an open -label (ie, observational ) manner. Unblinded recipients originall y randomized to
placebo areoffered BNT162b2 vaccination and thereafter followed in an open -label manne r.
Participants randomized to placebo who became eligible for vaccination with BNT162b2
(oranother COVID -19 vaccine) had the opportunity to receive BNT162b2 in a phased
manner as part of the study (no later than at the approximate time participants in Ph ase 2/3
reach Visit 4). The investigator ensured the participant met at least one of the
recommendation criteria. Any participant who originall y received placebo and subsequentl y
received BNT162b2 was moved to a new visit schedule to receive both doses of BNT162b2
at each of two additional vaccination visit s (Visits 101 and 102).
Sponsor and site personnel who are responsible for the ongoing conduct of the study remain
blinded to the data from participants whose treatment assignment hasnot been disclosed in
the ongoing study (ie, not unblinded) , with regard to individual participants’ randomization.
Safety evaluation for these participants by the study team remains blinded until a decision is
made to unblind the entire study . Aseparate (from study conduct) unblinded submissions
team is responsible for regulatory submissions.
All p articipants continue to be expected toremain in study follow -upfor a maximum of
approximately 2 years after Dose 2 of randomized study intervention .
2.5.1.2.3.2.2. Planned Studies
Further studies (or additional groups/anal yses from ongoing studies) are planned or ongoing,
including pediatric populations, maternal immunization, concomitant use with adult
pneumococcal and influenza vaccines, and obtaining blood samples for potential evaluatio n
for subclinical m yocarditis.
2.5.1.2.4. Proposed Indication
The proposed indication for BNT162b2 (30 µg) is:
Active immunization to prevent COVID -19 disease caused b y SARS -CoV -2 virus ,in
individuals ≥12 years of age .
2.5.1.2.5. Rationale for Candidate and Dose Selection
The final candidate and dose level (BNT162b2 at 30 µ g) was selected following review of
immunogenicit y and safety data from the dose -finding Phase 1 portion of Study C4591001
and review of nonclinical data. BNT162b2 at 30 µg proceeded into the Phase 2/3 portio n of
Study C4591001 because this dose and construct provided the optimum combination of a
favorable reactogenicit y profile and a robust immune response to afford protection against
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Page 18COVID -19in younger and older age groups (see Section 2.5.1.3 for a s ummary of regulatory
submissions, authorizations, and approvals) .
2.5.1.3. Regulatory Status
As of December 2021, BNT162b2 30- µg has received temporary authorization for
emergency use, conditional marketing authorization approval, or full approval in
>90countries globall y.Thename of the product supplied under emergency/temporary use
authorization for all applicable regions is Pfizer -BioNTech COVID-19 Vaccine. The
tradename of the product for all applicable regions is COMI RNATY .
United States
In the US, the vaccine is in clinical development under an IND application, BB-IND 19 ,736.
Fast Track Designation was granted on 07 July 2020 for individuals ≥18 years of age. The
initial Pediatric Study Plan (iPSP) was submitted to the FDA on 17 September 2020 and
FDA agreed with the final agreed PSP on 23 April 2021.
A summary regarding emergency use authorization status is provided below.
An EUA application was filed to the FDA on 20 November 2020 and the product was
authorized for emergency use in the US on 11 December 2020 as a primary series of
BNT162b2 30 µg for individuals ≥16 y ears of age (EUA 27034).
Authorization was granted on 10 May 2021 to expand use to individuals ≥12 y ears of
age.
Authorization was granted on 13 August 2021 for a third dose to be administered
≥28days following the second dose in individuals ≥12 y ears of age who have undergone
solid organ transplantation, or who are diagnosed with conditions that are considered to
have an equivalent level of immunocompromise.
A single booster dose was authorized on 22 September 2021 to be administered
≥6months after completing the primary serie sinindividuals ≥65years of age or 18 to
64years of age at high risk of severe COVID -19 or with frequent institutional or
occupational exposure to SARS -CoV -2.On20 October 2021 authorization was granted
for the use of a single booster dose as a heterologous booster dose following completion
of primary vaccination with another authorized COVID- 19 vaccine ( based on booster
eligibility criteria associated with the primary series vaccine received ).
Authorization was granted on 29 October 2021 to expand use to individuals 5 through
11years of age and for a manufacturing change to include an additional formulation of
the vaccine that uses Tris buffer instead of PBS.
On 19 November 2021, the eligible population for the homologous and heterologous
booster doses was expanded to individuals 18 y ears of age and older .
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Page 19On 9 December 2021, the eligible population for the homologous and heterologous
booster doses was expanded to individuals 16 y ears of age and older.
A summary regarding licensure status in the US is provided below.
The initial BLA for the 30 -µg formulation was submitted to US FDA on 18 May 2021 and
approved on 23 A ugust 2021 for individuals ≥16 years of age.
European Union
Arolling review for a Marketing Authorisation Application ( MAA) was initiated on
05 October 2020 with nonclinical data followed by Module 3 documents submitted on
05November 2020 and completed with submission of clinical modules on 07 December
2020 . A Paediatric Investigational Plan (PIP) was submitted to the Paediatric Committee
(PDCO) on 21 September 2020 and a decision on the agreement of the PIP was received 27
November 2020.
A summary regarding conditional approval status in the EU is provided b elow.
Conditional marketing approval was granted b y the European Medicines Agency (EMA)
on 21 December 2020 for administration of the primary series of BNT162b2 30 µg to
individuals ≥16years of age and was later expanded to include use in individuals
≥12years of age on 28 May 2021.
A booster dose (third dose) of BNT162b2 30 µg administered at least 6 months after the
second dose to individuals ≥18years of age was approved in the EU on 05October 2021;
on the same day , athird dose was approved in the EU to be administered at least 28 day s
after the second dose toindividuals who are severely immunocompromised .
An extension was approved on 26 November 2021 for administration of a primary series
of BNT162b2 10 µg to individuals 5 to 11 years of age, includ ing a third dose in severel y
immunocompromised individuals 5 y ears and older.
Rest of World
Marketing Authorization Applications were initiated beginning in October 2020 and
Conditional Marketing Authorizations have been granted in man y countries globall y
including Switzerland, Japan, Australia, New Zealand, and Brazil. Requests for
temporary authorization for emergency suppl y have also been filed and approved in man y
countries globally under emergency or temporary use authorization procedures or special
import procedures beginning in November 2020. The World Health Organization (WHO)
issued a positive opinion on the Emergency Use Listing of COMIRNATY on
31 December 2020. In addition to the approval of the US BLA on 23 August 2021, other
countries are also b eginning to grant full approval for COMIRNATY, including Canada
on 16 September 2021 and I srael on 19 September 2021.
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Page 202.5.1.4. Ethical Considerations
All studies in the clinical development program were conducted in compliance with the
ethical principles originating in or derived from the Declaration of Helsinki and in
compliance with all International Council on Harm onisation (I CH) Good Clinical Practice
(GCP) Guidelines. They were designed, performed, and anal yzed in accordance with all
applicable regulations, laws, and guidelines in effect at the time they were conducted from
the US FDA , EUDirective 2001/20/EC ,and local regulatory agencies in countries where the
study was conducted. T he study design reflect srecommendations from local review
boards/committees , andother local regulatory authorities.
The pivotal Phase 1/2/3 Study C4591001 was conducted at sites in the US, Brazil, Argentina,
Turkey , Sou th Africa, and German y; the majorit y of participants were enrolled at sites in the
US. The supporting Phase 1/2 Study BNT162 -01 was conducted at sites in German y.
Pediatric Study C4591007 was conducted at sites in the US, Finland, Poland, and Spain.
2.5.2. Overvi ew of Biopharmaceutics
2.5.2.1. Formulation Development
Two vaccine formulations are currentl y authorized.
PBS/Sucrose vaccine product : supplied as a preservative -free, sterile dispersion of LNPs in
aqueous cry oprotectant buffer formulated at 0.5 mg/mL in phosphate -buffered saline and
300mM sucrose at pH 7.4 to be diluted for IM administration. The presentation is diluted
with sterile 0.9% sodium chloride solution prior to use and delivers a 30 µg RNA dose for
individuals ≥12 y ears of age.
Tris/Sucrose vaccine prod uct: supplied as a preservative -free, sterile dispersion of LNPs in
aqueous cry oprotectant buffer for IM administration formulated at 0.1 mg/mL
RNA in10mM Tris buffer, 300 mM sucrose, pH 7.4.The presentation of the vaccine is:
30 µg RNA dose for individ uals ≥12 y ears of age, not for dilution
(0.3mLadministration)
10 µg RNA dose for individuals 5 through 11 years of age, requires dilution
(0.2mLadministration).
Details of formulation development and storage conditions are provided in Module 3.
2.5.2.2. Biopharmaceutical Studies
Not applicable.
2.5.2.3. Bioanalytical and Analytical Methods Used in Human Studies
Information on assay sused toassess SARS -CoV -2infection is in Module 2.7.1 Summary of
Biopharmaceutic Studies and Associated Anal ytical Methods .
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Page 212.5.3. Overvie w of Clinical Pharmacology
Not applicable.
2.5.4. Overview of Efficacy (Including Immunogenicity)
The methods and statistical anal yses for efficacy evaluation are summarized in
Section 2.5.4.1.1 and Section 2.5.4.1.2 , respectively, and results are in Section 2.5.4.3 .
Details of efficacy anal ysis methods in Study C4591001 are provided in the Module 5.3.5.1
C4591001 Protocol and statistical analysis plan (SAP).
2.5.4.1. Efficacy Endpoints and Analysis Methods
2.5.4.1.1. Efficacy Endpoints
Study C4591001 is the pivotal efficacy study for BNT162b2. Efficacy was assessed based on
confirmed cases of COVID -19 in the efficacy populations. Results from the protocol
specified interim analy sis conducted on an accrued 94 cases (data cutoff date:
04November 2020) and the final anal ysis conducted on an accrued 170 cases (data cutoff
date: 14 November 2020) were previousl y submitted. These anal yses included data from all
participants in Phase 3 age groups (12 -15, 16- 55, and >55 y ears of age) at the time of the
analyses. Prespecified primary and secondary efficacy endpoint analy ses were completed per
protocol as of 14 November 2020. At the time of the final anal ysis, there were relativel y few
participants 12 -15 years of age enrolled in the study and no COVID -19 cases in this age
group accrued at that time (14November 2020). Updated efficacy analy ses were presented
for adolescent participants 12- 15 years of age in the adolescent interim CSR dated
14April 2021 (through data cutoff date of 13 March 2021), and for participants ≥12 years of
age in the 6- month update interim CSR dated 29 April 2021 (through data cutoff date of
13March 2021) . Further u pdated efficacy anal yses in this COinclude cases in the
12-15years of age group accrued in blinded follow -up to a data cutoff date of
02September 2021 (see Section 2.5.4.1.2 ).
2.5.4.1.1.1. Efficacy Endpoints
The updated efficacy described and reported for adolescents 12 -15 years of age in this CO
include the following endpoint :
COVID -19 incidence per 1000 person- years of blinded follow -up based on central
laboratory or locally confirmed NAAT .
2.5.4.1.1.2. COVID -19 Case Determination
COVID -19 case determination methodology has not changed since the initial report of
vaccine efficacy for BNT162b2. Briefly , participants who developed an y potential
COVID -19 s ymptoms listed in the protocol were to contact the site immediately and if
confirmed to participate in an in -person or telehealth visit as soon as possible (optimally
within 3 day s of s ymptom onset, and at the latest 4 day s after s ymptom resolution). At the
visit (or prior to the visit, if a participant utilized a self- swab as permitted per protocol),
investigators were to collect clinical information and results from local standard-of- care tests
sufficient to confirm a COVID -19 diagnosis.
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Page 22Investigators were to obtain a nasal swab (mid-turbinate) for testing at a central laboratory
using a validated reverse transcription– polymerase chain reaction (RT -PCR) test (Cepheid;
EUA200047/A001) to detect SARS -CoV -2. If the evaluation was conducted by telehealth,
the pa rticipant was to self -collect a nasal swab and ship for assessment at the central
laboratory . Alocal NAAT result was only acceptable if it met protocol -specified criteria and
if a central laboratory result was not available. P articipants with andwithout evidence of
prior infection were determined by virological testing via NAAT on mid- turbinate swab and
serological testing for SARS- CoV -2 N-binding antibodies.
COVID -19 cases (defined per FDA guidance)13were based on SARS -CoV -2 positive test
result per central laboratory or local testing facility (using an acceptable test per protocol and
if no central laboratory result was available) and p resence of atleast 1 of the following :
Fever
New or increased cough
New or increased shortness of breath
Chills
New or increased muscle pain
New loss of taste or smell
Sore throat
Diarrhea
Vomiting.
Severe COVID -19cases (defined per FDA guidance)13included presence of at least 1 of the
following :
Clinical signs at rest indicative of severe s ystemic illness:
orespiratory rate ≥30 breaths per minute
oheart rate ≥125 beats per minute
oSpO 2≤93% on room air at sea level or PaO 2/FiO 2 <300 mm Hg
Respiratory failure:
oneeding high -flow oxygen
ononinvasive ventilation
omechanical ventilation
oextracorporeal membrane ox ygenation (ECMO )
Evidence of shock:
osystolic blood pressure <90 mm Hg
odiastolic blood pressure <60 mm Hg
orequiring vasopressors
Significant acute renal, hepatic, or neurologic dysfunction
Admission to an intensive care unit
Death.
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Page 23In addition to the above specified definition of severe COVID- 19, an efficacy anal ysis for
severe COVID -19 cases was conducted using the CDC definition of severe COVID- 19
(hospitalization, admission to the I CU, intubation or mechanical ventilation, or death ).14
2.5.4.1.2. Efficacy Analysis Methods
The statistical anal yses of efficacy data presented in this CO are from Study C4591001 and
were based on the evaluable efficacy and all-available population s.
Updated efficacy analy ses were conducted for efficacy endpoints using statistical methods
described in the stud y statistical analysis plan (Module 5.3.5.1 C4591001 SAP ). The point
estimate of V Eand associated 2 -sided 95% CI derived using the Clopper- Pearson method
adjusted for surveillance time were provided as a descriptive summary . Updated anal yses in
this COinclude COVI D-19 cases accrued inblinded follow -upin adolescents 12 -15 years of
age to the data cutoff date ( 02September 2021).
2.5.4.2. Immunogenicity Endp oints and Analysis Methods
Assay methods and qualification/validation reports for immunoassay s are provided in
Module 2.7.1 Summary of Biopharmaceutic Studies and Associated Anal ytical Methods .
Details of immunogenicity anal yses are summarized below. Stati stical analy sis methods are
provided in Section 2.5.4.2.2 .
2.5.4.2.1. Immunogenicity Endpoints
In Phase 3, an immunogenicity objective was to demonstrate noninferiorit y (NI)of the
immune response to prophy lactic BNT162b2 in participants 12 -15years of age compared to
participants 16 -25years of age who had no serological or virological evidence of past
SARS -CoV -2 infection. This NI anal ysis of neutralizing titers was performed to provide
immunobridging between these y ounger adolescents and young adults 16 -25 years of age.
Only a validated SARS -CoV -2 neutralization assay was used.
Immunogenicit y endp oints were anal yzed for SARS -CoV -2 serum neutralizing titers including:
geometric mean titers (GMT) in each age group and GMR of 12 -15years group to
16-25years group at 1 month after Dose 2
geometric mean -fold rise (GMFR) from before vaccination to 1 mon th after Dose 2 in
each age group
percentage of participants with a ≥4-fold rise in neutralizing titers (seroresponse)
from before vaccination to 1 month after Dose 2 in each age group.
2.5.4.2.2. Immunogenicity Analysis Methods
The statistical anal yses of immunogen icity data from Study C4591001 were based on the
evaluable immunogenicity populations and all -available immunogenicit y populations.
Immunogenicit y anal yses of neutralizing titers were conducted with the statistical methods
described in the stud y SAP (Modul e 5.3.5.1 C4591001 SAP ).
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Page 24NI was assessed based on the geometric mean ratio (GMR )of SARS -CoV -2 neutralizing titers
at 1 month after Dose 2 using a 1.5 -fold margin. The GMR and its 2 -sided 95% CI were
derived b y calculating differences in means and CIs on t he natural log scale of titers based on
Student’s t -distribution, then exponentiating the results. The difference in means on the natural
log scale was calculated as: (12 -15years of age) – (16-25 years of age). NI was declared if the
lower bound of the 2 -sided 95% CI for the GMR was >0.67.
2.5.4.3. Efficacy Results
2.5.4.3.1. Updated Analysis of Efficacy – Adolescents 12-15 Years of Age
Updated ef ficacy data for the Phase 3 portion of Study C4591001 were analy zed for all
participants 12-15 years of age who met the protocol -specified criteria for efficacy evaluation.
Data are summarized for the efficacy populations.
COVID -19 case evaluation for primary and secondary efficacy endpoints is discussed in
Section 2.5.4.1 . Efficacy endpoints evaluated confirmed COVID -19 cases in participants
either without or with or without evidence of prior SARS -CoV -2 infection before and during
vaccination regime n.
Efficacy population characteristics in the updated analysis are presented in Section 2.5.4. 3.1.1 ,
and results of the updated analysis are presented in Section 2.5.4.3.1.2 (VE against
COVID -19), and S ection 2.5.4.3.1.3 (VE against severe disease ).
2.5.4.3.1.1. Efficacy Populations –Updated Analysis
In the efficacy anal yses, adolescents in the efficacy populations included:
Evaluable efficacy population without evidence of SARS -CoV -2 infection prior to 7 days
after Dose 2: N=1057 in the BNT162b2 group and N= 1030 in the placebo group.
Evaluable efficacy population with or without evidence of SARS -CoV -2 infection prior to
7days after Dose 2: N=1119 in the BNT162b2 group an d N=11 09in the placebo group.
Dose 1 all -available efficacy population: N=1131 in the BNT162b2 group and N=1129 in
the placebo group.
The proportions of participants included in the updated efficacy populations were similar in
the BNT162b2 and placebo gro ups ( Table 1). There were 36 partic ipants ( 15 [1.3%] in the
BNT162b2 group and 21 [1.9%] in the placebo group )were excluded from the evaluable
efficacy (7days) population mostly because they did not receive all vaccinations as
randomized or did not receive Dose 2 within the predefined window (19 -42 day s after
Dose 1).
Demographics of participants (including sex, race, ethnicity , country , comorbidities, obesity
status, and age at vaccination) in the evaluable efficacy (7 day s) population for adolescent
participants without evidence of infection prior to 7 day s after Dose 2 were similar in the
BNT162b2 and placebo groups. Note that all adolescent participants 12 -15 years of age were
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Page 25from the US. This anal ysis population had generally similar demographics compared to the
safet y population (Section 2.5.5.2.1 ).
Demographic characteristics for the Dose 1 all -available efficacy population and for
participants with or without evidence of infection prior to 7 day s after Dose 2 (evaluable
efficacy [7 day s] population) were similar to those in the evaluable efficacy (7 day s)
population.
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Page 26Table 1.Efficacy Populations – Subjects 12 Through 15 Years of Age –Blinded
Placebo- Controll ed Follow -up Period
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
na(%)Placebo
na(%)Total
na(%)
Randomizedb1134 (100.0) 1130 (100.0) 2264 (100.0)
Dose 1 all -available efficacy population 1131 (99.7) 1129 (99.9) 2260 (99.8)
Subjects without evidence of infection before Dose 1 1083 (95.5) 1078 (95.4) 2161 (95.5)
Subjects excluded from Dose 1 all -available efficacy population 3 (0.3) 1 (0.1) 4 (0.2)
Reason for exclusionc
Did not receive at least 1 vaccination 3(0.3) 1 (0.1) 4 (0.2)
Dose 2 all -available efficacy population 1123 (99.0) 1117 (98.8) 2240 (98.9)
Subjects without evidence of infection prior to 7 days after Dose 2 1061 (93.6) 1037 (91.8) 2098 (92.7)
Subjects excluded from Dose 2 all -available efficacy population 11 (1.0) 13 (1.2) 24 (1.1)
Reason for exclusionc
Did not receive 2 vaccinations 10 (0.9) 13 (1.2) 23 (1.0)
Unblinded prior to 7 days after Dose 2 1 (0.1) 0 1 (0.0)
Evaluable efficacy (7 days) population 1119 (98.7) 1109 (98.1) 2228 (98.4)
Subjects without evidence of infection prior to 7 days after Dose 2 1057 (93.2) 1030 (91.2) 2087 (92.2)
Subjects excluded from evaluable efficacy (7 days) population 15 (1.3) 21 (1.9) 36 (1.6)
Reason for exclusionc
Randomized but did not meet all eligibility criteria 1 (0.1) 1 (0.1) 2 (0.1)
Did not receive all vaccinations as randomized or did not receive
Dose 2
within the predefined window (19 -42 days after Dose 1)14 (1.2) 19 (1.7) 33 (1.5)
Unblinded prior to 7 days after Dose 2 1 (0.1) 0 1 (0.0)
Had other important protocol deviations on or prior to 7 days after
Dose 20 3 (0.3) 3 (0.1)
a. n = Number of subjects with the specified characteristic.
b. These values are the denominators for the percentage calculations.
c. Subjects may have been excluded for more than 1 reason.
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Page 272.5.4.3.1.2. Vaccine Efficacy Against COVID -19 –Updated Analysis
2.5.4.3.1.2.1. Vaccine Efficacy From 7 Days After Dose 2 –Blinded Placebo- Controlled
Follow -Up Period
2.5.4.3.1.2.1.1. Participants Without Evidence of Infection Before and During
Vaccination Regimen
Among adolescent participants without evidence of SARS -CoV -2 infection before and
during the vaccination regimen, the estimated VE against confirmed COVID -19occurring at
least 7 days after Dose 2 was 100.0% (2 -sided 95% CI : 86.8%, 100.0%) , with 0 and 28 cases
in the BNT162b2 and placebo group s, respectivel y(Table 2).
The VE of BNT 162b2 for the same efficacy endpoint based on the Dose 2 all available
efficacy population was 100.0% (2-sided 95% CI: 87.2%, 100.0%), with 0 and 29 cases in
the BNT162b2 and placebo group, respectively .
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Page 28Table 2.Vaccine Efficacy – First COVID -19 Occurrence From 7 Days After Dose 2
–Blinded Placebo -Controlled Follow -up Period – Subjects 12 Through 15
Years of Age and Without Evidence of Infection Prior to 7 Days After Dose
2 –Evaluable Efficacy (7 Days) Population
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=1057)Placebo
(Na=1030)
Efficacy Endpoint
Subgroupn1bSurveillance
Timec(n2d)n1bSurveillance
Timec(n2d)VE (%) (95% CIe)
First COVID -19 occurrence from 7
days after Dose 20 0.343 (1043) 28 0.322 (1019) 100.0 (86.8, 100.0)
≥7 days after Dose 2 to <2 Months
after Dose 20 0.138 (1043) 15 0.133 (1019) 100.0 (73.2, 100.0)
≥2 Months after Dose 2 to <4 Months
after Dose 20 0.148 (1008) 10 0.139 (957) 100.0 (58.0, 100.0)
≥4 Months after Dose 2 0 0.057 (723) 3 0.050 (682) 100.0 (-112.1, 100.0)
Abbreviations: N -binding = SARS -CoV -2 nucleoprotein– binding; NAAT = nucleic acid amplification test;
SARS -CoV -2 = severe acute respiratory syndrome coronavirus 2; VE = vaccine efficacy.
Note: Subjects who had no serological or virological evidence (prior to 7 days after receipt of the last dose) of past SARS -
CoV -2 infection (ie, N -binding antibody [serum] negative at Visit 1 and SARS-CoV -2 not detected by NAAT [nasal swab]
at Visits 1 and 2, an d had negative NAAT (nasal swab) at any unscheduled visit prior to 7 days after Dose 2) were
included in the analysis.
a. N = number of subjects in the specified group.
b. n1 = Number of subjects meeting the endpoint definition.
c. Total surve illance time in 1000 person-years for the given endpoint across all subjects within each group at risk for
the endpoint. Time period for COVID -19 case accrual is from 7 days after Dose 2 to the end of the surveillance period for
the overall row and from start to the end of the range stated for each time interval.
d. n2 = Number of subjects at risk for the endpoint.
e. Confidence interval (CI) for VE is derived based on the Clopper and Pearson method adjusted for surveillance time.
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2.5.4.3.1.2.1.2. Participants With or Without Evidence of Infection Before and During
Vaccination Regimen
Among participants with or without evidence of SARS -CoV -2 infection before and during
the vaccination regimen, estimated VE against confirmed COVID -19 occurring at le ast
7days after Dose 2 was 100.0% (2 -sided 95% CI: 87.5%, 100.0%), with 0 and 30 cases in
the BNT162b2 and placebo groups, respectively (Table 3).For the 2 additional cases in
adolescent participants with evidence of SARS -CoV -2 infection (as compared with those
without evidence of infection from Table 2), both participants were SARS- CoV -2 negative at
baseline.
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Page 29Table 3.Vaccine Efficacy – First COVID -19 Occurrence From 7 Days After Dose 2
–Blinded Placebo -Controlled Follow -up Period – Subjec ts 12 Through 15
Years of Age and With or Without Evidence of Infection Prior to 7 Days
After Dose 2 –Evaluable Efficacy (7 Days) Population
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=1119)Placebo
(Na=1109)
Efficacy Endpoint
Subgroupn1bSurveillance
Timec(n2d)n1bSurveillance
Timec(n2d)VE (%) (95% CIe)
First COVID -19 occurrence from 7
days after Dose 20 0.362 (1098) 30 0.345 (1088) 100.0 (87.5, 100.0)
≥7 days after Dose 2 to <2 Months
after Dose 20 0.146 (1098) 17 0.142 (1088) 100.0 (76.4, 100.0)
≥2 Months after Dose 2 to <4 Months
after Dose 20 0.155 (1061) 10 0.148 (1022) 100.0 (57.4, 100.0)
≥4 Months after Dose 2 0 0.061 (767) 3 0.055 (726) 100.0 (-117.8, 100.0)
Abbreviation: VE = vaccine efficacy.
a. N = number of subjects in the specified group.
b. n1 = Number of subjects meeting the endpoint definition.
c. Total surveillance time in 1000 person -years for the given endpoint across all subjects within each group at risk for
the endpoint. Time period for COVID-19 case accrual is from 7 days after Dose 2 to the end of the surveillance period for
the overall row and from start to the end of the range stated for each time interval.
d. n2 = Number of subjects at risk for the end point.
e. Confidence interval (CI) for VE is derived based on the Clopper and Pearson method adjusted for surveillance time.
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2.5.4.3.1.2.1.3. Subgroup Analyses ( Vaccine Efficacy From 7 Days After Dose 2 –
Blinded Placebo -Controlled Follow -Up Period )
In the evaluable efficacy (7 day s) population, among participants without and with or without
evidence of SARS CoV -2 infection before and during the vaccination regimen, the estimated
VE was 100.0% for all subgroups bysex, race, ethnicity , country , comorbidi ties, andobesity
status. Due to the small number of participants, the data must be interpreted with caution.
2.5.4.3.1.2.2. All Confirmed Cases of COVID -19 After Dose 1 – All- Available Efficacy
Population
All reports of COVID -19 with onset at any time after Dose 1 are accounted for in (Table 4),
which provide s a summary of VE for all adolescent participants in the Dose 1 all-available
efficacy (modified intention -to-treat) population adjusted for exposure, regardless of
evidence of infection before or during the vaccination regimen. Among these participants, the
estimated VE against confirmed COVID -19 occurring after Dose 1 was 94.0% (2- sided 95%
CI: 81.3%, 98.8%), with 3 and 48 cases of COVID- 19 in the BNT162b2 and placebo groups,
respectivel y. All 3 cases in the BNT162b2 group occurred <11 days after Dose 1 and in
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Page 30participants who had baseline SARS -CoV -2 negative status, and represented all cases
reported in this group at any time.
The observed VE for BNT162b2 in adolescents in the Dose 1 all -available efficacy population
was 100.0% (ie, all cases were confined to the placebo group) for all time intervals starting
from ≥11days after Dose 1 to before Dose 2 through ≥4 months after Dose 2.
The early onset of protection is readily apparent in Figure 1, which display s cumulative
incidence for the first COVID -19 occurrence after Dose 1 among all vaccinated participants
based on Dose 1 all -available efficacy (modified intention -to-treat) popul ation. Disease onset
appears to track together for BNT162b2 and placebo until approximately 11 day s after
Dose 1 (consistent with the data shown in Table 4), at which poin t the curves diverge, with
cases steadil y accumulating in the placebo group, while remaining flat with no more cases in
the BNT162b2 group.
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Page 31Table 4.Vaccine Efficacy – First COVID -19 Occurrence After Dose 1 –Blinded
Placebo- Controlled Follow -up Period – Subjects 12 Through 15 Years of
Age –Dose 1 All -Available Efficacy Population
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=1131)Placebo
(Na=1129)
Efficacy Endpoint
Subgroupn1bSurveillance
Timec(n2d)n1bSurveillance
Timec(n2d)VE (%) (95% CIe)
First COVID -19 occurrence after Dose 1 3 0.450 (1109) 48 0.434 (1114) 94.0 (81.3, 98.8)
AfterDose 1 to before Dose 2 3 0.065 (1109) 12 0.065 (1114) 75.1 (7.6, 95.5)
After Dose 1 to <11 days after Dose 1 3 0.033 (1109) 4 0.033 (1114) 24.7 (-345.0, 89.0)
≥11 Days after Dose 1 to before Dose
20 0.032 (1106) 8 0.031 (1110) 100.0 (42.0, 100.0)
Dose 2 to 7 days after Dose 2 0 0.021 (1103) 5 0.021 (1100) 100.0 (-8.7, 100.0)
≥7 Days after Dose 2 0 0.364 (1102) 31 0.348 (1095) 100.0 (87.9, 100.0)
≥7 days after Dose 2 to <2 Months
after Dose 20 0.146 (1102) 17 0.143 (1095) 100.0 (76.3, 100.0)
≥2 Months after Dose 2 to <4 Months
after Dose 20 0.156 (1065) 10 0.149 (1029) 100.0 (57.3, 100.0)
≥4 Months after Dose 2 0 0.062 (770) 4 0.056 (732) 100.0 (-37.7, 100.0)
Abbreviation: VE = vaccine efficacy.
a. N =number of subjects in the specified group.
b. n1 = Number of subjects meeting the endpoint definition.
c. Total surveillance time in 1000 person -years for the given endpoint across all subjects within each group at risk for
the endpoint. Time peri od for COVID -19 case accrual is from Dose 1 to the end of the surveillance period for the overall
row and from start to the end of the range stated for each time interval.
d. n2 = Number of subjects at risk for the endpoint.
e. Confidence interval (CI) for VE is derived based on the Clopper and Pearson method adjusted for surveillance time.
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Page 32Figure 1.Cumulative Incidence Curves for the First COVID- 19 Occurrence After Dose 1 –Subjects 12 Through 15 Years of
Age –Blinded Placebo -Controlled Follow -up Period – Dose 1 All -Available Efficacy Population
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Page 332.5.4.3.1.2.2.1. Subgroup Analyses (All Confirmed Cases of COVID -19 After Dose 1 –
All-Available Efficacy Population )
Additionally , in subgroup anal yses for VE by sex, race, ethnicity , country , comorbidities, and
obesity status , the observed subgroup VEs based on the Dose 1 all -available efficacy
(modified intent -to-treat) popu lation were generally similar to those based on the evaluable
efficacy population except for a few subgroups that the number of participants and cases
were too small to provide robust estimates. The observed VEs for all subgroups were ≥88.7%
except for one subgroup (race, all others) with 1 case ineach group : American Indian or
Alaska native in placebo and Asian in BNT162b2 . Due to the small number of participants,
the data must be interpreted with caution.
2.5.4.3.1.3. Vaccine Efficacy Against Severe COVID -19 –Updated Analysis
No severe COVID -19 cases (per protocol definition or CDC criteria) were reported in
participants 12 15 years of age as of the data cutoff date (02 September 2021).
2.5.4.3.1.4. Variants of Concern
Among the 30 placebo participants with or without evide nce of SARS -CoV -2 infection
before and during the vaccination regimen and had COVID-19 cases, most variants
sequenced were neither VOI nor VOC except for the B.1.1.7 (Alpha) (Table 6), which was
found in 23.3% of placebo participants ( Table 5). There were no cases belonging to the Beta,
Gamma, Delta, Lambda, or Mu variants ( Table 6). Importantly , all of the cases in the
efficacy anal yses occurred between 02 November 2020 to 19 May 2021, which is before the
Delta surge in the US.
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Page 34Table 5.Summary of SARS -CoV -2 Variants for the First COVID -19 Occurrence
From 7 Days After Dose 2 –Blinded Placebo -Controlled Follow -up Period
–Subjects 12 Through 15 Years of Age and With or Without Evidence of
Infection Prior to 7 Days Afte r Dose 2 –Evaluable Efficacy (7 Days)
Population
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=0)Placebo
(Na=30)Total
(Na=30)
SARS -CoV -2 Lineageb
(WHO Classification)nc(%) nc(%) nc(%)
B.1 0 1 (3.3) 1 (3.3)
B.1.1.222 0 1 (3.3) 1 (3.3)
B.1.1.29 0 1 (3.3) 1 (3.3)
B.1.1.519 0 1 (3.3) 1 (3.3)
B.1.1.7 (Alpha) 0 7 (23.3) 7 (23.3)
B.1.142 0 1 (3.3) 1 (3.3)
B.1.2 0 10 (33.3) 10 (33.3)
B.1.243 0 1 (3.3) 1 (3.3)
B.1.361 0 1 (3.3) 1 (3.3)
B.1.369 0 1 (3.3) 1 (3.3)
B.1.400 0 1 (3.3) 1 (3.3)
B.1.427 0 2 (6.7) 2 (6.7)
B.1.526 0 1 (3.3) 1 (3.3)
Unknownd0 1 (3.3) 1 (3.3)
Abbreviation: SARS -CoV -2 = severe acute respiratory syndrome coronavirus 2.
a. N = number of subjects with first COVID -19 occurrence. This value is the denominator for the percentage
calculations.
b. Based on PANGO lineages (cov -lineages.org).
c. n = Number of subjects with the specified characteristic.
d. Include indeterminate result and not quantifiable (QNS) samples.
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Page 35Table 6.Summary of SARS -CoV -2 Variants of Concern or Variants of Interest for
the First COVID -19 Occurrence From 7 Days After Dose 2 –Blinded
Placebo- Controlled Follow -up Period – Subjects 12 Through 15 Years of
Age and With or Without Evidence of Infection Prior to 7 Days After Dose
2 –Evaluable Efficacy (7 Days) Population
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=0)Placebo
(Na=30)Total
(Na=30)
SARS -CoV -2 Lineageb
(WHO Classification)nc(%) nc(%) nc(%)
B.1.1.7 (Alpha) 0 7 (23.3) 7 (23.3)
B.1.351 (Beta) 0 0 0
P.1 (Gamma) 0 0 0
B.1.617.2 (Delta) 0 0 0
C.37 (Lambda) 0 0 0
B.1.621 (Mu) 0 0 0
Other 0 22 (73.3) 22 (73.3)
Unknownd0 1 (3.3) 1 (3.3)
Abbreviation: SARS -CoV -2 = severe acute respiratory syndrome coronavirus 2.
a. N = number of subjects with first COVID -19 occurrence. This value is the denominator for the percentage
calculations.
b. Based on PANGO lineages (cov -lineages.org).
c. n = Number of subjects with the specified characteristic.
d. Include indeterminate result and not quantifiable (QNS) samples.
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2.5.4.3.1.5. Efficacy Conclusions –Updated Analysis
Descriptive efficacy analy ses were conducted for the adolescent group on cases accrued
during blinded placebo -controlled follow -up period through the data cutoff date of
02September 2021.
In the adolescent group, in efficacy anal yses in the evaluable efficacy population based on
cases reported from at least 7 days after Dose 2 through the data cutoff date
(02September 2021), the estimated VE against confirmed COVID -19 was 100% (95% CI:
86.8%, 100%) for individuals without evidence of prior SARS -CoV -2 infection before and
during vaccination regimen, and 100% (2 -sided 95% CI : 87.5%, 100%) for those with or
without evidence of prior SARS -CoV -2 infection before and during vaccination regimen.
Among participants without and with or without evidence of SARS -CoV -2 infection before
and during the vaccination regimen ( evaluable efficacy population), VE against COVI D-19
occurring at least 7 day safter Dose 2 was evaluated for demographic and risk subgroups, and
the estimated VE was 100.0% for all subgroups.
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Page 36The efficacy anal ysis for the Dose 1 all -available (modified intention -to-treat) population,
included 3 cases in the BNT162b2 group (all occu rring within <11 day s after Dose 1 and in
participants who had baseline SARS -CoV -2 negative status ) and 48cases in the placebo
group, with an estimated VE against all cases occurring at an y time after Dose 1 of 94.0%
(2-sided 95% CI: 81.3%, 98. 8%).
No sev ere cases were reported in the 12 -15 years of age group as of the dat a cutoff date
(02September 2021) .
Most variants sequenced were neither Variant of Interest ( VOI)nor Variant of Concern
(VOC ) except for the B.1.1.7 (Alpha) found in 23.3% of placebo participants. All of the
cases in the efficacy analyses occurred between 02 November 2020 to 19 May 2021, which is
before the Delta surge in the US.
Overall, these updated efficacy data strongl y sup port BNT162b2 use in adolescents 12 -15years
of age.
2.5.4.4. Immunogenicity Results
2.5.4.4.1. Immunogenicity Populations
For immunogenicity analy ses, it was planned to select a random sample of 280 participants
in the BNT162b2 group for each of the two age groups (12-15 and 16-25 years of age) as an
immunogenicit y subset for the NI assessment. To maintain blinding of the laboratory
personnel, 50 participants in each placebo group were also randoml y selected from each of
the two age groups for serology testing.
The Dose 2 evaluable immunogenicit y population for adolescents 12 -15 years of age
included 209 participants in the BNT162b2 group and 36 participants in the placebo group),
and for young adults 16 -25 years of age included 186 participants in the BNT162b2 gro up
and 32 participants in the placebo group. The majority of participant exclusions from the
evaluable immunogenicity populations were due to participants not having at least 1 valid
and determinate immunogenicity result after Dose 2, mostly as the result of testing laboratory
supply limitation of the qualified viral lot and were generally balanced across age and
vaccine groups.
Demographics were generally similar for BNT162b2 and placebo, and between adolescents
and y oung adults 16 -25 years of age. Demogra phics of the evaluable immunogenicity
population were similar to those in the all- available immunogenicit y population andto those
in the corresponding safety population .
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Page 372.5.4.4.2. Noninferiority Between 12-15 Years of Age and 16- 25 Years of Age Groups
Geometric Mea n Ratio (GMR) in Neutralization Titers
The immune response to BNT162b2 in adolescents 12- 15 years of age was noninferior to that
observed in young adults 16- 25 years of age, based on SARS -CoV -2 50% neutralizing titers
at 1month after Dose 2, in participan ts without prior evidence of SARS -COV -2 infection,
and in fact greatl y exceeded the response observed in young adults. The GMT ratio of
adolescents to young adults was 1.76 (2-sided 95% CI : 1.47, 2.10), meeting the 1.5- fold NI
criterion (ie, lower bound of the 2 -sided 95% CI for GMR >0.67). Of note, the lower bound
of the 2- sided 95% CI for the GMR is >1 which indicates a statisticall y greater response in
the adolescents tha n that of y oung adults.
Seroresponse
Among participants without prior evidence of SARS -CoV -2 infection up to 1 month after
Dose 2 of BNT162b2, high proportions (97.9% of adolescents and 100.0% of y oung adults)
had a ≥4-fold rise (seroresponse) in SARS -CoV -2 50% neutralizing titers from before
vaccination to 1 month after Dose 2. The difference in proportions of participants who had a
≥4-fold rise between the two age groups (adolescents – young adults) was -2.1% (2 -sided
95% CI : -6.0%, 0.9%)
2.5.4.4.3. Immunogenicity Conclusions
Refer to Section 11.3 of the adolescent interim CSR dated 14 April 2021 (through data cutoff
date of 13 March 2021, Module 5.3.5.1 C4591001 Adolescent Interim CSR ) for full details
of immunogenicit y analyses for adolescent participants 12 -15 years of age , including results
foradditional immunogenicity endpoints which were anal yzed for SARS CoV -2 serum
neutralizing titers (GMTs, GMFRs, and sero response rate s).
In conclusion, immune response to BNT162b2 30 µg in SARS- CoV -2 50% neutralizing titers
in adolescents 12 -15 years of age was noninferior to (and in fact exceeded) the immune
response in young adults 16-25 years of age, which provides immunobridging for
adolescents. Substantial increases over baseline in neutralizing GMTs and high serorespon se
rates were observed at 1 month after Dose 2 in both age groups, which were observed for
participants with baseline SARSCoV -2 positive and negative status. The vast majority of
BNT162b2 recipients in both age groups achieved a ≥4-fold rises from before v accination to
1month after Dose 2.
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Page 382.5.5. Overview of Safety
The methods and statistical anal yses for safety evaluation are summarized in Section 2.5.5.1
and Section 2.5.5.1.2 , respectivel y, and results as of the data cutoff date ( 02 Septem ber 2021)
are presented in Section 2.5.5.2 .
Details of safety anal ysis methods in Study C4591001 are provided in the Module
5.3.5.1 C4591001 Protocol and SAP.
2.5.5.1. Safety Endpoints and Analysis Methods
2.5.5.1.1. Safety Endpoints
Reactogenicity
All participants 12-15 years of age and a subset of participants ≥16 y ears of age (y oung
adults 16- 25 years of age and adults 16- 55 years of age), were asked to record reactogenicit y
(referred as reactogenicity subset):15local reactions (pain, redness and swel ling at the
injection site), sy stemic events (fever, fatigue, headache, chills, vomiting, diarrhea, new or
worsened muscle pain, and new or worsened joint pain), and antip yretic/pain medication
usage for 7 days, each evening following administration of stu dy intervention using prompts
from an electronic diary (e-diary ). This allowed recording of these assessments only within a
fixed time window and provided an accurate representation of the participant’s experience at
that time. P articipant s were asked to assess local reactions and s ystemic events from Day 1
through Day 7 after each dose.
Adverse Events
Adverse events (AEs) were recorded for up to 1 month after Dose 2 and categorized by
frequency , maximum severity , seriousness, and relationship to study intervention using SOC
and PT according to MedDRA. Serious AEs (SAEs) will be recorded up to 6 months after
Dose 2. Deaths are recorded to the end of stud y.
Myocarditis and pericarditis were included as pre-specified adverse events of special inte rest
(AESI s) in Protocol Amendment 18 (07 September 2021).
Pfizer also utilizes a safety review as part of the signal detection processes that highlights
specified targeted medical events (TMEs) of clinical interest. TMEs are specific AE terms
reviewed on an ongoing basis by routine safet y data review procedures throughout the
clinical study . Although not prespecified in the protocol, TMEs are maintained in a separate
list as part of the Safet y Surveillance Review Plan for the vaccine program. By definition ,
TMEs are considered to be AESIs specific for a product or program's protocol(s). They are
based on review of known pharmacology , toxicology findings, possible class effects,
published literature, and potential signals arising from safet y data assessments.
The list of TMEs is customized for each development program and is d ynamic. For this
study , the list of TMEs includes events of interest because of their association with
COVID -19 and terms of interest for vaccines in general. Terms are chosen from the
MedDRA dictionary and may include PTs, high level term, high level group terms, or
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Page 39standardized MedDRA queries (SMQs; all evaluated as broad and narrow). Other events of
clinical i nterest identified by the sponsor in the reported safet y dataset were also reviewed
and summarized (Section 2.5.5.2.7 ).
Prior SARS -CoV -2 infection was determined b y virological testing via nucleic acid
amplification test ( NAAT) on mid-turbinate swab and serological testing for IgG to the
SARS -CoV -2 N-antigen at baseline, and via NAAT at Dose 2. P articipants were surveilled
for potential COVID -19 illness from Visit 1 onwards.
Pregnancies were reported for participants in an y phase of the stud y.
Narratives for safety events in adolescents (12 -15 years of age) are located in Module 5.3.5.1
C4591001 Adolescent 6- Month Update Int erim CSR Section 14 Narratives . Narratives for
this age group were prepared for participants if they had the following events:
deaths
Related SAEs
AEs leading to study discontinuation
AEs of clinical interest ( including anaphy laxis, appendicitis, Bell’s pa lsy)
pregnancy exposures
COVID -19 (participants with a case meeting severe criteria or >1 episode of COVID- 19)
2.5.5.1.2. Safety Analysis Methods
Safety data were anal yzed and reported using descriptive summary statistics for the safet y
population for each study phase .Anal yses were performed for endpoints described in
Section 2.5.5.1.1 .
Reactogenicity
Descriptive statistics were provided for each reactogenic ity endpoint for the reactogenicit y
subset after each dose for each vaccine group. Local reactions and systemic events from Day
1 through Day 7 after each vaccination are presented by severit y and cumulatively across
severit y levels. Descriptive summary st atistics included counts and percentages of
participants with the indicated endpoint and the associated Clopper -Pearson 2 -sided 95% CIs.
Missing reactogenicit y e-diary data were not imputed.
Adverse Events
Descriptive summary statistics including counts, p ercentages, and associated
Clopper -Pearson 2-sided 95% CI s were provided for AEs for each vaccination group .
AE anal yses of participants who had different durations of follow -up time due to unblinding in
the study (per protocol) were summarized as incidence rates (IR)adjusted for exposure time .
This wascalculated as: (number of participants reporting event ) /(total exposure time across
all participants in the specified group ). This account sfor variable exposure since unblinding
began for individ ual participants (as described in Section 2.5.1.2.3.2.1 ).Two-sided 95% CIs
for the IRswere provided based on Poisson distribution.
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Page 402.5.5.2. Safety Results
2.5.5.2.1. Safety Population s
The safet y population included a total of 2260participants who were 12- 15 years of age :
1131 participants in the BNT162b2 group and 1129 participants in the placebo group
(Table 7). Four participants were excluded from the safety population because they did not
receive an y stud y intervention.
Table 7.Safety Population – Phase 2/3 Subjects 12 Through 15 Years of Age
Vaccine Group (as Administered)
BNT162b2 (30 μg)
naPlacebo
naTotal
na(%)
Randomizedb2264
Vaccinated 1131 1129 2260 (99.8)
Safety population 1131 1129 2260 (99.8)
Excluded from safety population 4 (0.2)
Reason for exclusion
Subject did not receive study vaccine 4 (0.2)
a. n = Number of subjects with the specified characteristic, or the total sample.
b. This value is the denominator for the percentage calculations.
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2.5.5.2.1.1. Duration of Follow- Up
During the blinded placebo -controlled follow -up period, median follow -up time for
adolescent participants was 4 .4 months. There were 634 (56.1%) and 629 ( 55.7% )of
participants in the BNT162b2 and placebo groups, respectivel y, who had follow -up time ≥4
months to <6 months after Dose 2 ( Table 8). From Dose 2 t o the cutoff date, 740 (65.4%) of
participants in the BNT162b2 group had a total follow- up time ≥8 to <10 months, which was
composed of blinded and unblinded exposure . There were few participants (18 total) with
follow -up time of <6 months, as most adolescent participants 12-15 years of age should have
had ≥6 months of follow -up by the data cutoff date (02September 2021) , and also
corresponding with the number of participants who withdrew from the study (Table 10).
For original adolescent placebo recipients who received at least the first dose of BNT162b2,
median follow -up time was 3.8 months, and 65.0% of these participants had follow- up time
between ≥2 months to <4 months after Dose 1of BNT162b2 ( Table 9).
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Page 41Table 8.Follow -up Time After Dose 2 – Phase 2/3 Subjects 12 Through 15 Years of
Age –Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1131)
nb(%)Placebo
(Na=1129)
nb(%)Total
(Na=2260)
nb(%)
Original blinded placebo -controlled follow -up period
<2 Months 45 (4.0) 62 (5.5) 107 (4.7)
≥2-<4 Months 300 (26.5) 294 (26.0) 594 (26.3)
≥4-<6 Months 634 (56.1) 629 (55.7) 1263 (55.9)
≥6 Months 152 (13.4) 144 (12.8) 296 (13.1)
Mean (SD) 4.5 (1.24) 4.4 (1.27) 4.4 (1.26)
Median 4.4 4.4 4.4
Min, max (0.0, 10.8) (0.0, 9.1) (0.0, 10.8)
Total follow -up period from Dose 2 to cutoff date
<2 Months 8 (0.7)
≥2-<4 Months 0
≥4-<6 Months 10 (0.9)
≥6-<8 Months 326 (28.8)
≥8-<10 Months 740 (65.4)
≥10 Months 47 (4.2)
Mean (SD) 8.3 (1.03)
Median 8.4
Min, max (0.0, 10.9)
a. N = number of subjects in the specified group, or the total sample. This value is the denominator for the percentage
calculations.
b. n = Number of subjects with the specified characteristic.
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Page 42Table 9.Follow -up Time After Dose 1 of BNT162b2 –Phase 2/3 Subjects 12
Through 15 Years of Age (Subjects Who Originally Received Placebo) –
Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1010)
nb(%)
Open -label follow -upperiod
<2 Months 66 (6.5)
≥2-<4 Months 656 (65.0)
≥4-<6 Months 228 (22.6)
≥6 Months 60 (5.9)
Mean (SD) 3.8 (1.09)
Median 3.8
Min, max (0.1, 8.6)
a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. n = Number of subjects with the specified characteristic.
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2.5.5.2.1.2. Disposition
Blinded Placebo -Controlled Follow -Up Period
During the blinded placebo -controlled follow -up period, there were 3 (0.3%) participants in
the BNT162b2 group and 14 (1.2%) participants in the placebo group who discontinued from
the vaccination period (Dose 1 to 1 month after Dose 2) ( Table 10). Most particip ants
completed the visit at 1 month post -Dose 2 ( ≥97.0 %). Few participants in the BNT162b2 and
placebo groups were withdrawn from the study (0.4% and 1.2%, respectively ), and all we re
because of withdrawal by the participant, withdrawal by parent/guardian, or they were lost to
follow -up.
Open -Label Follow -Up Period
Individuals have been unblinded as they became locally eligible and wished to know their
vaccine assignment to confirm prior vaccination with BNT162b2 (if randomized to this
group), or to receive BNT162b2 (if randomized to placebo). Participants who originally
received BNT162b2 continued to be followed in an open- label manner. Participant swho
originall y received placebo were offered BNT162b2 vaccination (Doses 3 and 4 [first and
second dose of BNT162b2 30 µg, respectivel y]) and thereafter followed in an open- label
manner.
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Page 43Most participants in the BNT162b2 (98.1%) and placebo (97.0%) groups completed the
1month post-Dose 2 visit before unblinding (Table 10).
A total of 4 (0.4%) original BNT162b2 adolescent participants received Dose 1 of
BNT162b2 during the blinded placebo- controlled follow -up period and then received Dose 2
of BNT162b2 30 µg during the open- label follow -up period (when they were unblinded)
(Table 10). There were 45 (4.0%) participants withdrawn from the study , and most were
because of other reasons (21 of 23 participants were enrolled into Study C4591031 to
evaluate a booster dose of BNT162b2).
During the open- label follow -up period, most participants o riginally randomized to the
placebo group received Doses 3 and 4 (89.4% and 87.8%, first and second dose of
BNT162b2 30 µg, respectively ). There were 47 (4.2%) participants who were withdrawn
from the study after unblinding and before Dose 3. There were fe w participants in this group
(who received at least the first dose of BNT162b2 30 µg)who were withdrawn from the
study (0.5%) , and most were because of withdrawals by the participant, or they were lost to
follow -up ( Table 10).
Table 10. Disposition of All Randomized Subjects – Phase 2/3 Subjects 12 Through
15 Years of Age
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=1134)
nb(%)Placebo
(Na=1130)
nb(%)Total
(Na=2264)
nb(%)
Randomized 1134 (100.0) 1130 (100.0) 2264 (100.0)
Not vaccinated 3 (0.3) 1 (0.1) 4 (0.2)
Original blinded placebo -controlled follow -up period
Vaccinated 1131 (99.7) 1129 (99.9) 2260 (99.8)
Dose 1 1131 (99.7) 1129 (99.9) 2260 (99.8)
Dose 2 1124 (99.1) 1117 (98.8) 2241 (99.0)
Discontinued from original blinded placebo- controlled vaccination
periodc3 (0.3) 14 (1.2) 17 (0.8)
Reason for discontinuation
No longer meets eligibility criteria 0 7 (0.6) 7 (0.3)
Protocol deviation 0 2 (0.2) 2 (0.1)
Adverse event 1 (0.1) 0 1 (0.0)
Physician decision 1 (0.1) 0 1 (0.0)
Withdrawal by subject 0 1 (0.1) 1 (0.0)
Withdrawal by parent/guardian 0 1 (0.1) 1 (0.0)
Other 1 (0.1) 3 (0.3) 4 (0.2)
Unblinded before 1 -month post –Dose 2 visit 12 (1.1) 21 (1.9) 33 (1.5)
Completed 1 -month post –Dose 2 visit 1113 (98.1) 1096 (97.0) 2209 (97.6)
Withdrawn from the study 5 (0.4) 14 (1.2) 19 (0.8)
Withdrawn after Dose 1 and before Dose 2 0 0 0
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Page 44Table 10. Disposition of All Randomized Subjects – Phase 2/3 Subjects 12 Through
15 Years of Age
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=1134)
nb(%)Placebo
(Na=1130)
nb(%)Total
(Na=2264)
nb(%)
Withdrawn after Dose 2 and before 1 -month post –Dose 2 visit 0 3 (0.3) 3 (0.1)
Withdrawn after 1 -month post –Dose 2 visit 5 (0.4) 11 (1.0) 16 (0.7)
Reason for withdrawal from the study
Withdrawal by subject 1 (0.1) 7 (0.6) 8 (0.4)
Withdrawal by parent/guardian 1 (0.1) 5 (0.4) 6 (0.3)
Lost to follow -up 3 (0.3) 2 (0.2) 5 (0.2)
Open -label follow -up period
Originally randomized to BNT162b2 1107 (97.6)
Received Dose 2/unplanned dose 4 (0.4)
Completed 1 -month post –Dose 2 visit 15 (1.3)
Completed 6 -month post –Dose 2 visit 1065 (93.9)
Withdrawn from the study 45 (4.0)
Withdrawn before 6 -month post –Dose 2 visit 25 (2.2)
Withdrawn after 6 -month post –Dose 2 visit 20 (1.8)
Reason for withdrawal from the study
Withdrawal by subject 7 (0.6)
Withdrawal by parent/guardian 7 (0.6)
Lost to follow -up 6 (0.5)
Protocol deviation 1 (0.1)
No longer meets eligibility criteria 1 (0.1)
Other 23 (2.0)
Originally randomized to placebo 1108 (98.1)
Withdrawn from the study after unblinding and before Dose 3 47 (4.2)
Received Dose 3 (first dose of BNT162b2 [30 μg]) 1010 (89.4)
Received Dose 4 (second dose of BNT162b2 [30 μg]) 992 (87.8)
Discontinued from open -label vaccination periodd5 (0.4)
Reason for discontinuation from open -label vaccination period
Protocol deviation 4 (0.4)
Withdrawal by subject 1 (0.1)
Completed 1 -month post–Dose 4 visit 933 (82.6)
Withdrawn from the study 6 (0.5)
Withdrawn after Dose 3 and before Dose 4 5 (0.4)
Withdrawn after Dose 4 and before 1 -month post –Dose 4 visit 0
Withdrawn after 1 -month post –Dose 4 visit 1 (0.1)
Reason for withdrawal from the study
Withdrawal by subject 3 (0.3)
Lost to follow -up 2 (0.2)
Protocol deviation 1 (0.1)
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Page 45Table 10. Disposition of All Randomized Subjects – Phase 2/3 Subjects 12 Through
15 Years of Age
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=1134)
nb(%)Placebo
(Na=1130)
nb(%)Total
(Na=2264)
nb(%)
a. N = number of randomized subjects in the specified group, or the total sample. This value is the denominator for the
percentage calculations.
b. n = Number of subjects with the specified characteristic.
c. Original blinded placebo -controll ed vaccination period is defined as the time period from Dose 1 to 1 -month post –
Dose 2 visit.
d. Open -label vaccination period is defined as the time period from Dose 3 (first dose of BNT162b2 [30 µg]) to 1 -month
post–Dose 4 (second dose of BNT162b2 [ 30 µg]) visit.
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2.5.5.2.1.3. Demographics
Demographic characteristics for adolescents (12 -15 years of age) were similar in the
BNT162b2 and placebo groups in the safet y population, and all adolescents were enrolled at
sites in the United States (Table 11). Most adolesce nt participants in the BNT162b2 group
were White (85.8%), with 4.6% Black or African American participants and 6.4% Asian
participants, and other racial groups were ≤2.1%. There were 11.7% Hispanic/L atino
participants. The median age of adolescents in the BNT162b2 group was 14.0 years and
50.1% were male. Obese adolescents of this age group (based on age -and sex -specific BM I)
made up 11.3% (placebo group) to 12.6% (BNT162b2 group).
Overall, there were 96 (4.2%) and 2161 (95.6%) participants who were baseline
SARs- CoV -2 positive and negative, respectivel y (Table 11). Considering that the baseline
positive subgroup had fewer participants than the negative subgroup overall, t here were no
clinically meaningful differences in demographics in the 2 vaccine groups by SARS -CoV -2
status.
Adolescent participants had a diverse medical history profile consistent with that of
individuals in the general population in the same age group. For adolescents in the
BNT162b2 group, conditions in the immune sy stem disorders (399 [35.3%]; of which
241[21.3%] were seasonal allergy ); psychiatric disorders (293 [25.9%] , with frequentl y
reported PTs of attention deficit hy peractivity disorder (182 [16.1%]), anxiety (107 [9.5%]),
and depression (51 [4.5 %]); respiratory , thoracic, and mediastinal disorders (179 [15.8%]);
and skin and subcutaneous tissue disorders (170 [15.0%]) SOCs were most frequentl y
reported.
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Page 46There were 123 (10.9%) and 136 (12.0%) participants in the BNT162b2 and placebo groups,
respectivel y, who had any comorbidit y (per the Charlson comorbidity index), which was
mostly chronic pulmonary disease (119 [10.5%] and 127 [11.2%] participants, respectivel y).
Table 11.Demographic Characteristics – Phase 2/3 Subjects 12 Through 15 Years of
Age –Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1131)
nb(%)Placebo
(Na=1129)
nb(%)Total
(Na=2260)
nb(%)
Sex
Male 567 (50.1) 585 (51.8) 1152 (51.0)
Female 564 (49.9) 544 (48.2) 1108 (49.0)
Race
White 970 (85.8) 962 (85.2) 1932 (85.5)
Black or African American 52 (4.6) 57 (5.0) 109 (4.8)
All others 109 (9.6) 110 (9.7) 219 (9.7)
American Indian or Alaska Native 4 (0.4) 3 (0.3) 7 (0.3)
Asian 72 (6.4) 71 (6.3) 143 (6.3)
Native Hawaiian or other Pacific Islander 3 (0.3) 0 3 (0.1)
Multiracial 24 (2.1) 29 (2.6) 53 (2.3)
Not reported 6 (0.5) 7 (0.6) 13 (0.6)
Racial designation
Japanese 5 (0.4) 2 (0.2) 7 (0.3)
Ethnicity
Hispanic/Latino 132 (11.7) 130 (11.5) 262 (11.6)
Non-Hispanic/non -Latino 997 (88.2) 996 (88.2) 1993 (88.2)
Not reported 2 (0.2) 3 (0.3) 5 (0.2)
Country
USA 1131 (100.0) 1129 (100.0) 2260 (100.0)
Baseline SARS -CoV -2 status
Positivec46 (4.1) 50 (4.4) 96 (4.2)
Negatived1083 (95.8) 1078 (95.5) 2161 (95.6)
Missing 2 (0.2) 1 (0.1) 3 (0.1)
Comorbiditiese
Yes 249 (22.0) 242 (21.4) 491 (21.7)
No 882 (78.0) 887 (78.6) 1769 (78.3)
Obesef
Yes 143 (12.6) 128 (11.3) 271 (12.0)
No 988 (87.4) 1001 (88.7) 1989 (88.0)
Age at vaccination (years)
Mean (SD) 13.6 (1.11) 13.6 (1.11) 13.6 (1.11)
Median 14.0 14.0 14.0
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Page 47Table 11.Demographic Characteristics – Phase 2/3 Subjects 12 Through 15 Years of
Age –Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1131)
nb(%)Placebo
(Na=1129)
nb(%)Total
(Na=2260)
nb(%)
Min, max (12, 15) (12, 15) (12, 15)
Abbreviation: SARS -CoV -2 = severe acute respiratory syndrome coronavirus 2.
a. N = number of subjects in the specified group, or the total sample. This value is the denominator for the percentage
calculations.
b. n = Number of subjects with the specified characteristic.
c. Positive N -binding antibody result at Visit 1, positive NAAT result at Visit 1, or medical history of COVID -19.
d. Negative N -binding antibody result at Visit 1, negative NAAT result at Visit 1, and no medical history of COVID -19.
e. Number of subjects who have 1 or more comorbidities that increase the risk of severe COVID -19 disease: defined as
subjects who had at least one of the Charlson comorbidity index category or BMI ≥95thpercentile.
f.Obese is defined as BMI ≥95thpercentile from the growth chart. Refer to the CDC growth char ts at
https://www.cdc.gov/growthcharts/html charts/bmiagerev htm.
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2.5.5.2.1.3.1. Participants With at Least 6 Months Follow -Up Time –BNT162b2 Group
Demographic characteristics for all original BNT162b2 recipients 12-15years of age and
having at least 6 months of follow- up time after Dose 2 were similar to demographic
characteristics in the BNT162b2 group overall ( Table 11).
2.5.5.2.1.3.2. Original Placebo Recipients 12 Through 15 Years of Age Who Then
Received BNT162b2
Demographic characteristics for all original placebo recipients 12-15 years of age who then
received BNT162b2 later during the open -label follow -up period were similar to
demographic characteristics in the placebo group overall ( Table 11).
2.5.5.2.2. Reactogenicit y
There are no new reactogenicity data presented in this submission since the adolescent
interim CSR, dated 14 April 2021.
The majority of reactogenicity events previously reported in adolescent participants were
mild or moderate in severity and short -lived after dosing (ie, median onset mostly between 1 -
3 day s after dosi ng and resolution within 1 -3 day s after onset) (full details in Sections 12.1.1
and 12.1.2 of the adolescent interim C4591001 CSR dated 14 April 2021).
2.5.5.2.3. Adverse Events
AE safet y data are from either the blinded placebo -controlled follow -up period, the
open -label observational follow -up period, or both. The time periods and safety anal ysis
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Page 48groups are presented below and in Figure 2. AEs reported from Dose 1 to 1 month after
Dose 2 during the blinded placebo- controlled follow -up period were previously reported in
the adolescent interim CSR, dated 14 April 2021. For each time period, overall safety will be
presented in addition to new AEs that were reported s ince the EUA snapshot occurred (based
on a data cutoff date of 13 March 2021), in the following order:
Blinded placebo- controlled follow -up p eriod from Dose 1 to the unblinding date,
including separate summaries for new AEs that were reported after the EUA snapshot
date ( Section 2.5.5.2.3.1 )
Open -label follow -up period –original BNT162b2 recipients ( Section 2.5.5.2.3.2 )
Blinded placebo -controlled and open -label follow -up periods from Dose 1 to
6months after Dose 2 – original BNT162b2 participants, including separate
summaries for new AEs that were reported after the EUA snapshot date
(Section 2.5.5.2.3.3 )
Open -label follow -up period – original placebo recipients who then received at least
1 dose of BNT162b2 after unblinding ( Section 2.5.5.2.3.4 )
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Page 49Figure 2.Phase 2/3 Safety Analyses of Adolescent Participants: Time Periods and
Analysis Groups
2.5.5.2.3.1. Blinded Placebo- Controlled Follow -Up Period From Dose 1 to the
Unblinding Date (Adverse Events)
2.5.5.2.3.1.1. Summary of Adverse Events (Blinded Placebo- Controlled Follow -Up
Period From Dose 1 to the Unblinding Date )
An overview of AE IRs adjusted for exposure time from Dose 1 to the unblinding date for
adolescent participants during the blinded placebo -controlled follow -up period is presented in
Table 12, and total exposure time in 100 PY was similar in the BNT162b2 and placebo
groups (4.6 vs 4.5 per 100 PY, respectivel y). Hence, frequencies aresummarized in the
safet y results .
The percentage of adolescent participants with any AE was similar in the BNT162b2 and
placebo groups (8.4% and 10.0%, respectively). Severe AEs, SAEs, and AEs leading to
withdrawal were reported by ≤1.1%, ≤0.9%, and ≤0.1%, respectively , in both groups. All
reported SAEs were assessed by the investigator as not related to study intervention.
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Page 50Withdrawals due to related AEs were reported in 1 adolescent participant in the BNT162b2
group (p yrexia occurring 1 day after Dose 1; previously reported in adolescent interim CSR
dated 14 April 2021, Section 12.3.2.4.1), and none in the placebo group. There were no
deaths.
Table 12. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date –Blinded Placebo -Controlled Follow -up Period – Phase 2/3 Subjects
12 Through 15 Years of Age –Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1131, TEb=4.6)Placebo
(Na=1129, TEb=4.5)
Adverse Event nc(%) IRd(95% CIe) nc(%) IRd(95% CIe)
Any event 95(8.4) 20.8 (16.8, 25.4) 113(10.0) 25.1 (20.7, 30.1)
Relatedf36(3.2) 7.9 (5.5, 10.9) 24(2.1) 5.3 (3.4, 7.9)
Severe 13(1.1) 2.8 (1.5, 4.9) 5(0.4) 1.1 (0.4, 2.6)
Life-threatening 2(0.2) 0.4 (0.1, 1.6) 1(0.1) 0.2 (0.0, 1.2)
Any serious adverse event 10(0.9) 2.2 (1.0, 4.0) 2(0.2) 0.4 (0.1, 1.6)
Relatedf0 0.0 (0.0, 0.8) 0 0.0 (0.0, 0.8)
Severe 7(0.6) 1.5 (0.6, 3.2) 1(0.1) 0.2 (0.0, 1.2)
Life-threatening 1(0.1) 0.2 (0.0, 1.2) 1(0.1) 0.2 (0.0, 1.2)
Any nonserious adverse event 89(7.9) 19.5 (15.6, 24.0) 111(9.8) 24.6 (20.3, 29.6)
Relatedf36(3.2) 7.9 (5.5, 10.9) 24(2.1) 5.3 (3.4, 7.9)
Severe 6(0.5) 1.3 (0.5, 2.9) 4(0.4) 0.9 (0.2, 2.3)
Life-threatening 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Any adverse event leading to
withdrawal1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Relatedf1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Severe 0 0.0 (0.0, 0.8) 0 0.0 (0.0, 0.8)
Life-threatening 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Death 0 0.0 (0.0, 0.8) 0 0.0 (0.0, 0.8)
a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. TE = total exposure time in 100 person -years across all subjects in the specified group. Exposure time for a subject is
the time from Dose 1 to the end of the blinded follow -up period. This value is the denominator for the incidence rate
calculation.
c. n = Number of subjects reporting at least 1 occurrence of the specified event category. For "any event," n = number of
subjects reporting at least 1 occurrence of any event.
d. Incidence rate (IR) is calculated as number of subjects reporting the event/total exposure time in 100 person -years
(PY) across all subjects in the specified group.
e. 2-sided CI based on Poisson d istribution.
f.Assessed by the investigator as related to investigational product.
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Page 51Subgroup Analyses (Summary of Adverse Events [ Blinded Placebo -Controlled Follow -
Up Period From Dose 1 to the Unblinding Date ])
Total exposure time in 100 PY was similar in the BNT162b2 and placebo groups for each
subgroup anal ysis.
There were 4 (8.7%) and 91 (8.4%) participants who were baseline SARS -CoV -2 positive
and negative in the BNT162b2 group who reported at least 1 AE, respectively , and 4 (8.0%)
and 109 (10.1%) participants who were baseline SARS -CoV -2 positive and negative in the
placebo group who reported at least 1 AE, respectively . The frequency of severe AEs, SAEs
(all assessed as not related), or AEs leading to withdrawal in participants who were
SARS -CoV -2 neg ative was 1.2%, 0.9%, and 0.1%, respectivel y, while there were no severe
AEs, SAEs, or AEs leading to withdrawal in participants who were SARS -CoV -2 positive,
supporting previous observations in this study that participants who are SARS -CoV -2
positive at baseline do not report AEs at a higher rate than those who are negative at baseline
(previousl y reported in 6- month update interim CSR, dated 29 April 2021) .
The frequency of at least 1 AE reported in the BNT162b2 group was 6.8% in
Hispanic/Latino and 8.6% in non -Hispanic/non -Latino participants. The frequency of related
AEs, severe AEs, SAEs (all not related), and AEs leading to withdrawal was similar in the
Hispanic/Latino and Non -Hispanic/Non-Latino subgroups. Considering that the
Hispanic/Latino subgrou p (N=132) had fewer participants than the non- Hispanic/non -Latino
subgroup (N=99 7) in the BNT162b2 group, the small numerical differences in these
subgroups were not considered clinically meaningful.
The frequency of at least 1 AE reported in the BNT162b2 group was 5.8% to 8.6% across
race subgroups. Related AEs were reported in the BNT162b2 group across race subgroups at
frequencies of 1.9% to 5.5%. L ow incidences of severe and serious AEs were reported in the
BNT162b2 groups across race subgroups ( ≤1.9%).Considering that some race subgroups
had fewer participants than others (within the BNT162b2 groups: White N=970, Black or
African American N=52, and ‘All Others’ N=109), the small numerical differences in these
subgroups were not considered clinically meaningful.
The frequency of at least 1 AE reported in the BNT162b2 group for males and females was
7.4% and 9.4%, respectively , and the corresponding frequency in the placebo group was
9.7% and 10.3%, respectively . In the BNT162b2 group, frequencies of at l east 1 SAE in male
and female participants were 0.5% and 1.2% in the BNT162b2 group and 0.3% and none in
the placebo group, respectively .
2.5.5.2.3.1.2. Analysis of Adverse Events (Blinded Placebo -Controlled Follow -Up Period
From Dose 1 to the Unblinding Date)
Adverse E vents by System Organ Class and Preferred Term ( Blinded Placebo -
Controlled Follow -Up Period From Dose 1 to the Unblinding Date )
AEs from Dose 1 to the unblinding date during the blinded placebo -controlled follow -up
period are presented in Table 13. AEs reported i n adolescents were similar in the BNT162b2
and placebo groups (8.4% and 10.0%, respectively). The most frequently reported AEs in the
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Page 52BNT162b2 gr oup included ly mphadenopathy (9 [0.8%]), injection site pain (8 [0.7%]),
fatigue (8 [0.7%]), py rexia (6 [0.5%]), depression (6 [0.5%]) nausea (5 [0.4%]), and headache
(5[0.4%]). Most of these AEs were previousl y reported in the adolescent interim CSR, date d
14April 2021.
The number of participants with psy chiatric disorder AEs were comparable in the 2 groups,
(17 [1.5%] in BNT162b2 group vs. 13 [1.2%] in placebo group) ( Table 13). There were 4
participants who were hospitalized with the event of suicidal ideation (3 of these were new
after the EUA snaps hot and are discussed in Section 2.5.5.2.5.1.1 ; the remaining case that
was previousl y reported in the adolescent interim CSR, dated 14 April 2021 is discussed in
Section 2.5.5.2.5.1 ). All participants were in the BNT162b2 group and had an ongoing past
medical history of depression and/or anxiety (3diagnosed within 2020 and 1 since 2018). Of
these 4 participants, 3 had been taking selective serotonin reuptake inhibitors (fluoxetine or
sertraline) for their ongoing condition. The fourth participant had their concomitant
medication for attention deficit hy peractivity disorder changed from methy lphenidate
hydrochloride to demethy lphenidate hy drochloride approximately 22 day s before the event of
suicidal ideation occurred.
A total of 9 participants reported depression: 6 [0.5%] in the BNT162b2 group and 3 [0.3%]
in the placebo group (Table 13), (6 of these were new after the EUA snapshot; 4 in the
BNT162b2 group and 2 in the placebo group [Table 15]). Of the 6 participants in the
BNT162b2 group 3 participants had a known past medical history of ongoing depression, and
of the 4 newl y diagnosed cases in the BNT162b2 group, 3 participants had an ongoing past
medical history of attention deficit hy peractivity disorder and the depression for the
remaining participant in this group was reported to be due to social events. Within the
placebo group, 2 of the 3 participants were newl y diagnosed wi th depression (Table 13and
Table 15, respectivel y).
The event of conversion diso rder(BNT162b2 group) has been previousl y reported in the
adolescent interim CSR dated 14 April 2021 Section 12.4.2.1.1 as an SAE of neuralgia and
had been extensively investigated. Further follow -up since the adolescent interim CSR :the
participant was co ntinuing with ph ysical therap y and had undergone further neurological
examination and investigations including an MRI brain scan with and without contrast that
was normal. There has been little change in her symptoms, and she continues to require
treatment .
The 1 participant in the BNT162b2 group who reported a tic had an exacerbation of their
known tic disorder (diagnosed since 2019) and was considered to be due to life stressors (as
determined b y the principal investigator) . This event was previousl y reported in the
adolescent interim CSR dated 14 April 2021 .
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Page 53Table 13. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term –Blinded Placebo -
Controlled Follow -up Period – Phase 2/3 Subjects 12 Through 15 Years of
Age –Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1131, TEb=4.6)Placebo
(Na=1129, TEb=4.5)
System Organ Class
Preferred Termnc(%)IRd(95% CIe) nc(%) IRd(95% CIe)
Any event 95(8.4) 20.8 (16.8, 25.4) 113(10.0) 25.1 (20.7, 30.1)
BLOOD AND LYMPHATIC SYSTEM DISORDERS 9(0.8) 2.0 (0.9, 3.7) 2(0.2) 0.4 (0.1, 1.6)
Lymphadenopathy 9(0.8) 2.0 (0.9, 3.7) 2(0.2) 0.4 (0.1, 1.6)
CONGENITAL, FAMILIAL AND GENETIC
DISORDERS0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Spine malformation 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
EAR AND LABYRINTH DISORDERS 1(0.1) 0.2 (0.0, 1.2) 3(0.3) 0.7 (0.1, 1.9)
Cerumen impaction 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Conductive deafness 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Ear pain 1(0.1) 0.2 (0.0, 1.2) 1(0.1) 0.2 (0.0, 1.2)
EYE DISORDERS 2(0.2) 0.4 (0.1, 1.6) 1(0.1) 0.2 (0.0, 1.2)
Eye pain 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Eyelid rash 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Retinal haemorrhage 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
GASTROINTESTINAL DISORDERS 14(1.2) 3.1 (1.7, 5.1) 8(0.7) 1.8 (0.8, 3.5)
Abdominal pain 2(0.2) 0.4 (0.1, 1.6) 1(0.1) 0.2 (0.0, 1.2)
Aphthous ulcer 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Constipation 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Diarrhoea 3(0.3) 0.7 (0.1, 1.9) 1(0.1) 0.2 (0.0, 1.2)
Gastritis 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Lip swelling 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Mouth swelling 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Mouth ulceration 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Nausea 5(0.4) 1.1 (0.4, 2.6) 3(0.3) 0.7 (0.1, 1.9)
Oral mucosal blistering 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Rectal prolapse 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Tooth impacted 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Toothache 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Vom iting 1(0.1) 0.2 (0.0, 1.2) 1(0.1) 0.2 (0.0, 1.2)
GENERAL DISORDERS AND ADMINISTRATION
SITE CONDITIONS17(1.5) 3.7 (2.2, 6.0) 12(1.1) 2.7 (1.4, 4.6)
Chills 2(0.2) 0.4 (0.1, 1.6) 1(0.1) 0.2 (0.0, 1.2)
Fatigue 8(0.7) 1.7 (0.8, 3.4) 4(0.4) 0.9 (0.2, 2.3)
Injection site pain 8(0.7) 1.7 (0.8, 3.4) 8(0.7) 1.8 (0.8, 3.5)
Injection site swelling 2(0.2) 0.4 (0.1, 1.6) 0 0.0 (0.0, 0.8)
Nodule 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Oedema peripheral 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
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Page 54Table 13. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term –Blinded Placebo -
Controlled Follow -up Period – Phase 2/3 Subjects 12 Through 15 Years of
Age –Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1131, TEb=4.6)Placebo
(Na=1129, TEb=4.5)
System Organ Class
Preferred Termnc(%)IRd(95% CIe) nc(%) IRd(95% CIe)
Peripheral swelling 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Pyrexia 6(0.5) 1.3 (0.5, 2.9) 0 0.0 (0.0, 0.8)
Vessel puncture site pain 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
IMMUNE SYSTEM DISORDERS 1(0.1) 0.2 (0.0, 1.2) 1(0.1) 0.2 (0.0, 1.2)
Food allergy 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Seasonal allergy 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
INFECTIONS AND INFESTATIONS 10(0.9) 2.2 (1.0, 4.0) 9(0.8) 2.0 (0.9, 3.8)
Anal abscess 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Appendicitis 0 0.0 (0.0, 0.8) 2(0.2) 0.4 (0.1, 1.6)
Body tinea 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Candida infection 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Cellulitis 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Conjunctivitis 0 0.0 (0.0, 0.8) 2(0.2) 0.4 (0.1, 1.6)
Ear infection 3(0.3) 0.7 (0.1, 1.9) 0 0.0 (0.0, 0.8)
Focal peritonitis 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Infectious mononucleosis 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Otitis externa 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Otitis media 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Paronychia 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Pilonidal cyst 1(0.1) 0.2 (0.0, 1.2) 1(0.1) 0.2 (0.0, 1.2)
Subcutaneous abscess 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Tinea capitis 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Vulval abscess 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Vulvovaginal mycotic infection 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
INJURY, POISONING AND PROCEDURAL
COMPLICATIONS15(1.3) 3.3 (1.8, 5.4) 25(2.2) 5.5 (3.6, 8.2)
Accident 1(0.1) 0.2 (0.0, 1.2) 1(0.1) 0.2 (0.0, 1.2)
Ankle fracture 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Bone contusion 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Clavicle fracture 1(0.1) 0.2 (0.0, 1.2) 1(0.1) 0.2 (0.0, 1.2)
Concussion 3(0.3) 0.7 (0.1, 1.9) 4(0.4) 0.9 (0.2, 2.3)
Contusion 2(0.2) 0.4 (0.1, 1.6) 2(0.2) 0.4 (0.1, 1.6)
Fall 2(0.2) 0.4 (0.1, 1.6) 5(0.4) 1.1 (0.4, 2.6)
Femur fracture 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Foot fracture 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Hand fracture 1(0.1) 0.2 (0.0, 1.2) 4(0.4) 0.9 (0.2, 2.3)
Humerus fracture 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
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Page 55Table 13. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term –Blinded Placebo -
Controlled Follow -up Period – Phase 2/3 Subjects 12 Through 15 Years of
Age –Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1131, TEb=4.6)Placebo
(Na=1129, TEb=4.5)
System Organ Class
Preferred Termnc(%)IRd(95% CIe) nc(%) IRd(95% CIe)
Ligament sprain 1(0.1) 0.2 (0.0, 1.2) 4(0.4) 0.9 (0.2, 2.3)
Lip injury 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Meniscus injury 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Muscle strain 1(0.1) 0.2 (0.0, 1.2) 1(0.1) 0.2 (0.0, 1.2)
Patella fracture 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Procedural pain 2(0.2) 0.4 (0.1, 1.6) 3(0.3) 0.7 (0.1, 1.9)
Radius fracture 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Skin laceration 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Tibia fracture 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Tooth fracture 0 0.0 (0.0, 0.8) 2(0.2) 0.4 (0.1, 1.6)
Upper limb fracture 1(0.1) 0.2 (0.0, 1.2) 1(0.1) 0.2 (0.0, 1.2)
INVESTIGATIONS 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
SARS -CoV -2 antibody test positive 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
MUSCULOSKELETAL AND CONNECTIVE
TISSUE DISORDERS8(0.7) 1.7 (0.8, 3.4) 14(1.2) 3.1 (1.7, 5.2)
Arthralgia 2(0.2) 0.4 (0.1, 1.6) 4(0.4) 0.9 (0.2, 2.3)
Back pain 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Joint swelling 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Musculoskeletal chest pain 1(0.1) 0.2 (0.0, 1.2) 1(0.1) 0.2 (0.0, 1.2)
Myalgia 3(0.3) 0.7 (0.1, 1.9) 2(0.2) 0.4 (0.1, 1.6)
Neck pain 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Osteochondrosis 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Pain in extremity 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Tendonitis 0 0.0 (0.0, 0.8) 4(0.4) 0.9 (0.2, 2.3)
NEOPLASMS BENIGN, MALIGNANT AND
UNSPECIFIED (INCL CYSTS AND POLYPS)1(0.1) 0.2 (0.0, 1.2) 3(0.3) 0.7 (0.1, 1.9)
Fibroadenoma of breast 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Hair follicle tumour benign 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Melanocytic naevus 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Skin papilloma 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
NERVOUS SYSTEM DISORDERS 13(1.1) 2.8 (1.5, 4.9) 13(1.2) 2.9 (1.5, 4.9)
Dizziness 2(0.2) 0.4 (0.1, 1.6) 1(0.1) 0.2 (0.0, 1.2)
Headache 5(0.4) 1.1 (0.4, 2.6) 7(0.6) 1.6 (0.6, 3.2)
Migraine 3(0.3) 0.7 (0.1, 1.9) 0 0.0 (0.0, 0.8)
Paraesthesia 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Presyncope 1(0.1) 0.2 (0.0, 1.2) 4(0.4) 0.9 (0.2, 2.3)
Syncope 1(0.1) 0.2 (0.0, 1.2) 1(0.1) 0.2 (0.0, 1.2)
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Page 56Table 13. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term –Blinded Placebo -
Controlled Follow -up Period – Phase 2/3 Subjects 12 Through 15 Years of
Age –Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1131, TEb=4.6)Placebo
(Na=1129, TEb=4.5)
System Organ Class
Preferred Termnc(%)IRd(95% CIe) nc(%) IRd(95% CIe)
PSYCHIATRIC DISORDERS 17(1.5) 3.7 (2.2, 6.0) 13(1.2) 2.9 (1.5, 4.9)
Anxiety 4(0.4) 0.9 (0.2, 2.2) 6(0.5) 1.3 (0.5, 2.9)
Attention deficit hyperactivity disorder 2(0.2) 0.4 (0.1, 1.6) 4(0.4) 0.9 (0.2, 2.3)
Conversion disorder 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Depression 6(0.5) 1.3 (0.5, 2.9) 3(0.3) 0.7 (0.1, 1.9)
Disorientation 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Generalised anxiety disorder 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Obsessive -compulsive disorder 0 0.0 (0.0, 0.8) 2(0.2) 0.4 (0.1, 1.6)
Panic attack 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Sleep terror 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Suicidal ideation 4(0.4) 0.9 (0.2, 2.2) 0 0.0 (0.0, 0.8)
Tic 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
RENAL AND URINARY DISORDERS 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Dysuria 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
REPRODUCTIVE SYSTEM AND BREAST
DISORDERS1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
Amenorrhoea 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
RESPIRATORY, THORACIC AND MEDIASTINAL
DISORDERS3(0.3) 0.7 (0.1, 1.9) 8(0.7) 1.8 (0.8, 3.5)
Epistaxis 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Nasal congestion 2(0.2) 0.4 (0.1, 1.6) 3(0.3) 0.7 (0.1, 1.9)
Rhinorrhoea 2(0.2) 0.4 (0.1, 1.6) 4(0.4) 0.9 (0.2, 2.3)
Sneezing 1(0.1) 0.2 (0.0, 1.2) 0 0.0 (0.0, 0.8)
SKIN AND SUBCUTANEOUS TISSUE
DISORDERS9(0.8) 2.0 (0.9, 3.7) 16(1.4) 3.5 (2.0, 5.8)
Acne 2(0.2) 0.4 (0.1, 1.6) 3(0.3) 0.7 (0.1, 1.9)
Dermatitis contact 2(0.2) 0.4 (0.1, 1.6) 1(0.1) 0.2 (0.0, 1.2)
Eczema 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Pityriasis rosea 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Rash 3(0.3) 0.7 (0.1, 1.9) 5(0.4) 1.1 (0.4, 2.6)
Rash maculo -papular 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Seborrhoeic dermatitis 0 0.0 (0.0, 0.8) 1(0.1) 0.2 (0.0, 1.2)
Urticaria 2(0.2) 0.4 (0.1, 1.6) 5(0.4) 1.1 (0.4, 2.6)
SURGICAL AND MEDICAL PROCEDURES 1(0.1) 0.2 (0.0, 1.2) 1(0.1) 0.2 (0.0, 1.2)
Wisdom teeth removal 1(0.1) 0.2 (0.0, 1.2) 1(0.1) 0.2 (0.0, 1.2)
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Page 57Table 13. Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term –Blinded Placebo -
Controlled Follow -up Period – Phase 2/3 Subjects 12 Through 15 Years of
Age –Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1131, TEb=4.6)Placebo
(Na=1129, TEb=4.5)
System Organ Class
Preferred Termnc(%)IRd(95% CIe) nc(%) IRd(95% CIe)
Note: MedDRA (v24.0) coding dictionary applied.
a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. TE = total exposure time in 100 person -years across all subjects in the specified group. Exposure time fo r a subject is
the time from Dose 1 to the end of the blinded follow -up period. This value is the denominator for the incidence rate
calculation.
c. n = Number of subjects reporting at least 1 occurrence of the specified event. For "any event," n = num ber of subjects
reporting at least 1 occurrence of any event.
d. Incidence rate (IR) is calculated as number of subjects reporting the event/total exposure time in 100 person -years
(PY) across all subjects in the specified group.
e. 2-sided CI base d on Poisson distribution.
PFIZER CONFIDENTIAL SDTM Creation: 05OCT2021 (18:29) Source Data: adae Table Generation: 03NOV2021
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Subgroup Analyses (Adverse Events by System Organ Class and Preferred Term
[Blinded Placebo -Controlled Follow -Up Period From Dose 1 to the Unblinding Date ])
For the baseline SARS -CoV -2 positive and negative subgroups, AEs by SOC and PT were
similar to those in the overall safety population. Considering that the positive subgroup
(N=46) had fewer participants than the negative subgroup (N=1083) in the BNT162b2 group,
differences in SOCs were considered not clinically meaningful, and th ere is no evidence that
individuals who are positive at baseline report AEs at a higher frequency than those who are
negative at baseline.
For the ethnicit y subgroups, AEs by SOC and PT were similar to those in the overall safet y
population for Hispanic/La tino and non- Hispanic/non -Latino participants. Considering that
the Hispanic/Latino subgroup (N=132) had fewer participants than non -Hispanic/non -Latino
subgroup (N=99 7) in the BNT162b2 group, differences in AEs b y SOC and PT in these
subgroups were not cl inically meaningful.
For race subgroups, AEs by SOC and PT were similar to those in the overall safet y
population. Considering that some race subgroups had fewer participants than others (within
the BNT162b2 groups: White N=970, Black or African American N=52, and ‘All Others’
N=109), differences in AEs by SOC and PT in these subgroups were not clinically
meaningful.
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Page 58For sex subgroups, AEs by SOC and PT were similar to those in the overall safet y
population. There was a slightly higher frequency of any event reported in the BNT162b2
group in female participants compared to males (53 [9.4%], 42 [7.4%] respectivel y), and of
any SAEs 7 (1.2%) females, 3 (0.5%) males. Within the placebo group there were 2 (0.3%)
SAEs reported in male participants and none in the females. In the BNT162b2 group,
lymphadenopathy was reported in 8 (1.4%) male participants and in 1 (0.2%) female
participant. AEs in the psy chiatric disorders SOC were reported in 12 (2.1%) female
participants compared to 5 (0.9%) male participants. De pression was the most frequentl y
reported event in both sexes (4 [0.7%] females and 2 [0.4%] males). Anxiety was reported in
4 (0.7%) females and no males. Suicidal ideation was the next most frequently reported
event: in females, 3 [0.5%], 1 (0.2%) in males.
Related Adverse Events –Blinded Placebo -Controlled Follow -Up Period From Dose 1 to the
Unblinding Date
From Dose 1 to the unblinding date, adolescent participants with AEs assessed as related by
the investigator were similar in the BNT162b2 and placebo groups (36 [3.2%] and 24 [2.1%],
respectivel y). Most related AEs were reactogenicity events and in the SOC of general
disorders and administration site conditions, reported by 16 (1.4%) and 10 (0.9%)
participants in the BNT162b2 and placebo groups, respectivel y.
Related events of l ymphadenopathy were reported in 7 (0.6%) adolescents in the BNT162b2
group and 1 (0.1%) adolescent in the placebo group (refe r to other significant AEs in Section
2.5.5.2.7 ).
Immediate Adverse Events – Blinded Placebo -Controlled Follow -Up Peri od From Dose 1 to
the Unblinding Date
Adolescents with immediate AEs were low in frequency (≤0.4%) after either dose of study
intervention. All immediate AEs after Dose 1 were in the SOCs of general disorders and
administration site conditions (injection site pain, injection site ery thema, and vessel
puncture site pain) and nervous s ystem disorders (dizziness and headache).
After Dose 2, most immediate AEs were in the SOC of general disorders and administration
site conditions (injection site pain, injecti on site bruising, injection site hyperesthesia,
fatigue, chills; 1-2 participants reporting each). Other immediate AEs after Dose 2 were
reported in the SOC of nervous s ystem disorders (dizziness; 1 participant in the BNT162b2
adolescent group) or skin and subcutaneous tissue disorders (rash maculo -papular;
1 participant in the placebo adolescent group).
No allergic AEs were reported after either dose of BNT162b2 within 30 minutes after
vaccination.
Severe or Life -Threatening Adverse Events –Blinded Placeb o-Controlled Follow -Up Period
From Dose 1 to the Unblinding Date
From Dose 1 to the unblinding date, severe AEs were reported in 13 (1.1%) adolescent
participants in the BNT162b2 group and 5 (0.4%) participants in the placebo group.
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Page 59The following severe e vents in the psy chiatric orders SOC were previousl y reported in the
adolescent interim CSR, dated 14 April 2021 :
One participant in the BNT162b2 group reported an SAE each of anxiety and
depression (discussed in Section 2.5.5.2.5.1 )
One participant in the BNT162b2 group reported 2 SAEs of depression (first SAE
discussed in Section 2.5.5.2.5.1 ). The second SAE was a new case not previously
reported and occurred after the EUA snapshot (discussed in Section 2.5.5.2.5.1.1 ).
One participant in the BNT162b2 group reported an SAE of suicidal ideation
(discussed in Section 2.5.5.2.5.1 ).
Certain severe events discussed below are new cases which have not been previously
reported :
One participant in the placebo group reported a severe AE of urticaria (discussed in
Section 2.5.5.2.3.1.3 )
One participant in the BNT162b2 group reported a severe SAE of anal abscess
(discussed in Section 2.5.5.2.5.1.1 ).
One participant in the BNT162b2 group reported an SAE of suicidal ideation
(discussed in Section 2.5.5.2.5.1.1 ).
There were 3 participants (2 in the BNT162b2 and 1 in the placebo group) who reported at
least 1 life-threatening (or Grade 4) AE from Dose 1 to the unblinding date.
The following life -threatening events were previously reported in the adolescent interim
CSR, dated 14 April 2021:
One participant in the placebo group reported an SAE each of focal peritonitis and
appendicitis ( discussed in Section 2.5.5.2.5.1 ).
One participant in the BNT162b2 group reported a Grade 4 AE of p yrexia (40.4°C)
on Day 2 after Dose 1, with temperature returning to normal on Day 4. The AE was
assessed b y the investigator as related to stud y intervention, resolved, and the
participant withdrew from the study .
The life -threatening event below is a new case and has not been previously reported:
One participant in the BNT162b2 group reported a life -threatening (Grade 4) SAE of
suicidal ideation, which was a new event after the EUA snapshot (discussed in
discussed in Section 2.5.5.2.5.1.1 )
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Page 602.5.5.2.3.1.3. New Adverse Events Since EUA Snapshot (Blinded Placebo -Controlled
Follow -Up Period From Dose 1 to the Unblinding Date)
Summary of New Adverse Events Since EUA Snapshot (Blinded Placebo -Contro lled
Follow -Up Period From Dose 1 to the Unblinding Date)
The frequency of adolescent participants in the BNT162b2 group with an y new AE after the
EUA snapshot from Dose 1 to the unblinding date was 2. 6%, which was less than the
frequency in the placebo group (4.2%) (Table 14). There were 6 (0.5%) participants in the
BNT162b2 group with SAEs, and all events were assess ed by the investigator as not related
to study intervention. No SAEs were reported in the placebo group. There were no
withdrawals because of any AEs or deaths.
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Page 61Table 14.Number (%) of Subjects Reporting at Least 1 New Adverse Event After the
EUA Snap shot, From Dose 1 to Unblinding Date – Blinded Placebo -
Controlled Follow -up Period – Phase 2/3 Subjects 12 Through 15 Years of
Age –Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1130)Placebo
(Na=1126)
Adverse Event nb(%) (95% CIc) nb(%) (95% CIc)
Any event 29(2.6) (1.7, 3.7) 47(4.2) (3.1, 5.5)
Relatedd3(0.3) (0.1, 0.8) 3(0.3) (0.1, 0.8)
Severe 5(0.4) (0.1, 1.0) 2(0.2) (0.0, 0.6)
Life-threatening 1(0.1) (0.0, 0.5) 0 (0.0, 0.3)
Any serious adverse event 6(0.5) (0.2, 1.2) 0 (0.0, 0.3)
Relatedd0 (0.0, 0.3) 0 (0.0, 0.3)
Severe 4(0.4) (0.1, 0.9) 0 (0.0, 0.3)
Life-threatening 1(0.1) (0.0, 0.5) 0 (0.0, 0.3)
Any nonserious adverse event 24(2.1) (1.4, 3.1) 47(4.2) (3.1, 5.5)
Relatedd3(0.3) (0.1, 0.8) 3(0.3) (0.1, 0.8)
Severe 1(0.1) (0.0, 0.5) 2(0.2) (0.0, 0.6)
Life-threatening 0 (0.0, 0.3) 0 (0.0, 0.3)
Any adverse event leading to withdrawal 0 (0.0, 0.3) 0 (0.0, 0.3)
Relatedd0 (0.0, 0.3) 0 (0.0, 0.3)
Severe 0 (0.0, 0.3) 0 (0.0, 0.3)
Life-threatening 0 (0.0, 0.3) 0 (0.0, 0.3)
Death 0 (0.0, 0.3) 0 (0.0, 0.3)
Abbreviation: EUA = emergency use authorization.
a. N = number of subjects in the specified group, subjects who withdrew from the study before EUA snapshot
25Mar2021 with the cutoff date 13Mar2021 are not included. This value is the denominator for the percentage
calculations.
b. n = Number of s ubjects reporting at least 1 occurrence of the specified event category. For "any event," n = number of
subjects reporting at least 1 occurrence of any event.
c. Exact 2 -sided CI based on the Clopper and Pearson method.
d. Assessed by the investi gator as related to investigational product.
PFIZER CONFIDENTIAL SDTM Creation: 05OCT2021 (17:29) Source Data: adae Table Generation: 11NOV2021
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New Adverse Events Since EUA Snapshot by System Organ Class and Preferred Term
(Blinded Placebo -Controlled Follow -Up Period From Dose 1 to the Unblinding Date)
New AEs after the EUA snapshot from Dose 1 to the unblinding date during the blinded
placebo- controlled follow -up period are presented in Table 15.
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Page 62The most frequentl y reported AEs in adolescents were in the ps ychiatri c disorders SOC
(11[1.0%] and 9 [0.8%] adolescent participants in the BNT162b2 and placebo groups,
respectivel y). These cases are discussed alongside cumulative cases during this period in
Section 2.5.5.2.3.1.2 (Adverse Events b y System Organ Class) .
One participant in the BNT162b2 group reported a panic attack. This participant had a past
medical history of attention deficit hy peractivity disorder since 2016. They had ongoing
panic attacks starting 60 day s post Dose 2 which was considered not related and attributed to
social/environmental events. The event was nonserious, and the participant has continued in
the study .
Table 15.Number (%) of Subjects Reporting at Least 1 New Adverse Event After the
EUA Snapshot, From Dose 1 to Unblinding Date, by System Organ Class
and Preferred Term –Blinded Placebo -Controlled Follow -up Period –
Phase 2/3 Subjects 12 Through 15 Ye ars of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1130)Placebo
(Na=1126)
System Organ Class
Preferred Termnb(%) (95% CIc) nb(%) (95% CIc)
Any event 29(2.6) (1.7, 3.7) 47(4.2) (3.1, 5.5)
CONGENITAL, FAMILIAL AND GENETIC DISORDERS 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Spine malformation 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
EAR AND LABYRINTH DISORDERS 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Conductive deafness 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
EYE DISORDERS 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Eye pain 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
GASTROINTESTINAL DISORDERS 1 (0.1) (0.0, 0.5) 5 (0.4) (0.1, 1.0)
Nausea 0 (0.0, 0.3) 2 (0.2) (0.0, 0.6)
Abdominal pain 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Constipation 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Mouth ulceration 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Tooth impacted 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Vomiting 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
GENERAL DISORDERS AND ADMINISTRATION SITE
CONDITIONS1 (0.1) (0.0, 0.5) 1 (0.1) (0.0, 0.5)
Injection site pain 1 (0.1) (0.0, 0.5) 1 (0.1) (0.0, 0.5)
Chills 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Fatigue 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Injection site swelling 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Pyrexia 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
IMMUNE SYSTEM DISORDERS 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Seasonal allergy 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
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Page 63Table 15.Number (%) of Subjects Reporting at Least 1 New Adverse Event After the
EUA Snapshot, From Dose 1 to Unblinding Date, by System Organ Class
and Preferred Term –Blinded Placebo -Controlled Follow -up Period –
Phase 2/3 Subjects 12 Through 15 Ye ars of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1130)Placebo
(Na=1126)
System Organ Class
Preferred Termnb(%) (95% CIc) nb(%) (95% CIc)
INFECTIONS AND INFESTATIONS 3 (0.3) (0.1, 0.8) 1 (0.1) (0.0, 0.5)
Anal abscess 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Cellulitis 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Paronychia 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Pilonidal cyst 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
INJURY, POISONING AND PROCEDURAL COMPLICATIONS 6 (0.5) (0.2, 1.2) 13 (1.2) (0.6, 2.0)
Fall 1 (0.1) (0.0, 0.5) 4 (0.4) (0.1, 0.9)
Hand fracture 0 (0.0, 0.3) 4 (0.4) (0.1, 0.9)
Procedural pain 2 (0.2) (0.0, 0.6) 1 (0.1) (0.0, 0.5)
Concussion 0 (0.0, 0.3) 2 (0.2) (0.0, 0.6)
Ligament sprain 0 (0.0, 0.3) 2 (0.2) (0.0, 0.6)
Upper limb fracture 1 (0.1) (0.0, 0.5) 1 (0.1) (0.0, 0.5)
Ankle fracture 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Bone contusion 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Contusion 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Femur fracture 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Meniscus injury 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Skin laceration 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Tibia fracture 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
INVESTIGATIONS 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
SARS -CoV -2 antibody test positive 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
MUSCULOSKELETAL AND CONNECTIVE TISSUE
DISORDERS1 (0.1) (0.0, 0.5) 6 (0.5) (0.2, 1.2)
Tendonitis 0 (0.0, 0.3) 4 (0.4) (0.1, 0.9)
Arthralgia 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Back pain 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Musculoskeletal chest pain 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED
(INCL CYSTS AND POLYPS)0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Melanocytic naevus 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
NERVOUS SYSTEM DISORDERS 1 (0.1) (0.0, 0.5) 6 (0.5) (0.2, 1.2)
Headache 0 (0.0, 0.3) 3 (0.3) (0.1, 0.8)
Presyncope 0 (0.0, 0.3) 2 (0.2) (0.0, 0.6)
Migraine 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Syncope 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
PSYCHIATRIC DISORDERS 11 (1.0) (0.5, 1.7) 9 (0.8) (0.4, 1.5)
Anxiety 3 (0.3) (0.1, 0.8) 4 (0.4) (0.1, 0.9)
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Page 64Table 15.Number (%) of Subjects Reporting at Least 1 New Adverse Event After the
EUA Snapshot, From Dose 1 to Unblinding Date, by System Organ Class
and Preferred Term –Blinded Placebo -Controlled Follow -up Period –
Phase 2/3 Subjects 12 Through 15 Ye ars of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1130)Placebo
(Na=1126)
System Organ Class
Preferred Termnb(%) (95% CIc) nb(%) (95% CIc)
Depression 4 (0.4) (0.1, 0.9) 2 (0.2) (0.0, 0.6)
Attention deficit hyperactivity disorder 2 (0.2) (0.0, 0.6) 3 (0.3) (0.1, 0.8)
Suicidal ideation 3 (0.3) (0.1, 0.8) 0 (0.0, 0.3)
Obsessive -compulsive disorder 0 (0.0, 0.3) 2 (0.2) (0.0, 0.6)
Panic attack 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
RENAL AND URINARY DISORDERS 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Dysuria 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
REPRODUCTIVE SYSTEM AND BREAST DISORDERS 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Amenorrhoea 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
RESPIRATORY, THORACIC AND MEDIASTINAL
DISORDERS1 (0.1) (0.0, 0.5) 4 (0.4) (0.1, 0.9)
Nasal congestion 1 (0.1) (0.0, 0.5) 3 (0.3) (0.1, 0.8)
Epistaxis 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Rhinorrhoea 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Sneezing 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
SKIN AND SUBCUTANEOUS TISSUE DISORDERS 2 (0.2) (0.0, 0.6) 3 (0.3) (0.1, 0.8)
Acne 1 (0.1) (0.0, 0.5) 1 (0.1) (0.0, 0.5)
Dermatitis contact 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Eczema 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Rash 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Seborrhoeic dermatitis 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Urticaria 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
SURGICAL AND MEDICAL PROCEDURES 1 (0.1) (0.0, 0.5) 1 (0.1) (0.0, 0.5)
Wisdom teeth removal 1 (0.1) (0.0, 0.5) 1 (0.1) (0.0, 0.5)
Abbreviation: EUA = emergency use authorization.
Note: MedDRA (v24.0) coding dictionary applied.
Note: Adverse events that occurred on the day of or after subjects were unblinded are excluded from this summary.
a. N = number of subjects in the specified group, subjects who withdrew from the study before EUA snapshot
25Mar2021 with the cutoff date 13Mar2021 are not included. This value is the denominator for the percentage
calculations.
b. n = Number of subjects reporting at least 1 occurrence of the specified event. For "any event," n = number of subjects
reporting at least 1 occurrence of an y event.
c. Exact 2 -sided CI based on the Clopper and Pearson method.
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Page 65New Related Adverse Events Since EUA Snapshot (Blinded Placebo -Controlled Follow -
Up Period From Dose 1 to the Unblinding Date)
There were few adolescent participants with new related AEs that occurred after the EUA
snapshot in both the BNT162b2 and placebo groups (3 [0.3%] participants each), and each
PT was reported b y 1participant each in either group.
One participant in the B NT162b2 group reported an AE of musculoskeletal chest pain
(verbatim term reported was bilateral rib pain), on Day 3 after Dose 2. The AE was moderate
in severity and resolved the same day . There is no evidence that the investigator had
evaluated the parti cipant for cardiac disease.
New Severe or Life -Threatening Adverse Events Since EUA Snapshot (Blinded
Placebo- Controlled Follow -Up Period From Dose 1 to the Unblinding Date)
New severe AEs after the EUA snapshot were reported in 5 (0.4%) adolescent partici pants in
the BNT162b2 group and 2 (0.2%) participants in the placebo group (Table 16).
Certain sever e events are discussed below:
One participant in the placebo group reported a severe AE of urticaria on Day 55 after
Dose 2 with a duration of 8 day s, and the AE was assessed by the investigator as not
related to stud y intervention. The participant had a past medical history of penicillin
allergy since 2008. The event was nonserious, resolved, and the participant continued
in the study , receiving a first dose of BNT162b2 with no further urticaria reported.
One participant in the BNT162b2 group reported a second severe SAE of depression
(previousl y had a severe SAE and reported in the adolesecent interim CSR, dated
14April 2021 and discussed in Section 2.5.5.2.5.1 ; second SAE discussed in
Section 2.5.5.2.5.1.1 ).
One participant in the BNT162b2 group reported a severe SAE of suicidal ideation
(discussed in Section 2.5.5.2.5.1.1 ).
One participant in the BNT162b2 group reported a severe SAE of anal abscess
(discussed in Section 2.5.5.2.5.1.1 ).
From Dose 1 to the unblindin g date, there was 1 participant in the BNT162b2 group who
reported a life-threatening (or Grade 4) SAE of suicidal ideation (discussed in
Section 2.5.5.2.5.1.1 ).
All new severe and life -threatening events reported after the EUA snapshot from Dose 1 to
the unblinding date were assessed b y the investigator as not related to stud y intervention.
Most were resolved as of the data cutoff date (02 September 2021). For additional safety data
after the EUA snapshot during blinded placebo -controlled and open -label follow -up periods
for original BNT162b2 recipients 12through 15 years of age, refer to Section 2.5.5.2.3.3.3 .
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Page 66Table 16.Number (%) of Subjects Reporting at Least 1 New Severe Adverse Event
After the EUA Snapshot, From Dose 1 to Unblinding Date, by System
Organ Class and Preferred Term –Blinded Placebo- Controlled Follow -up
Period – Phase 2/3 Subjects 12 Through 15 Years of Age –Safety
Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1130)Placebo
(Na=1126)
System Organ Class
Preferred Termnb(%) (95% CIc) nb(%) (95% CIc)
Any event 5(0.4) (0.1, 1.0) 2(0.2) (0.0, 0.6)
INFECTIONS AND INFESTATIONS 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Anal abscess 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
INJURY, POISONING AND PROCEDURAL
COMPLICATIONS2 (0.2) (0.0, 0.6) 1 (0.1) (0.0, 0.5)
Femur fracture 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Procedural pain 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Upper limb fracture 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
PSYCHIATRIC DISORDERS 2 (0.2) (0.0, 0.6) 0 (0.0, 0.3)
Depression 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Suicidal ideation 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
SKIN AND SUBCUTANEOUS TISSUE DISORDERS 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Urticaria 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Abbreviation: EUA = emergency use authorization.
Note: MedDRA (v24.0) coding dictionary applied.
Note: Adverse events that occurred on the day of or after subjects were unblinded are excluded from this summary.
a. N = number of subjects in the specified group, subjects who withdrew from the study before EUA snapshot
25Mar2021 with the cutoff date 13Mar2021 are not included. This value is the denominator for the percentage
calculations.
b. n = Number of subjects reporting at least 1 occurrence of the specified event. For "any event," n = number of subjects
reporting at least 1 occurrence of an y event.
c. Exact 2 -sided CI based on the Clopper and Pearson method.
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2.5.5.2.3.2. Open -Label Follow -Up Period From the Unblinding Date to the Data Cutoff
Date –Original BNT162b2 Recipients (Adverse Events)
2.5.5.2.3.2.1. Summary of Adverse Events (Open -Label Follow -Up Period From the
Unblinding Date to the Data Cutoff Date –Original BNT162b2 Recipients )
An overview of AEs from the unblinding date to the data cutoff date for adolescent
participants who originally received BNT162b2 during the open -label follow -up period is
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Page 67presented in Table 17(Note: Per prot ocol, AEs are reported through approximately 1 month
after Dose 2 and within 48 hours after a blood draw. S AEs are reported to approximately
6months after the last dose of study intervention.)
There were 18 (1.6%) participants who experienced an y AE, including 0.4%, 0.3%, and 0%
who experienced related, severe, and life -threatening events, respectivel y (Table 17). This is
marke dly reduced relative to AEs from Dose 1 to the unblinding date (8.4% of BNT162b2
participants experienced any AE, including 3.2%, 1.1%, and 0.2% who ex perienced related,
severe, and life -threatening events, respectivel y [Table 12]. The frequenci es of SAEs and
AEs leading to withdrawal during the open -label follow -up period (0.4% and 0%,
respectivel y [Table 17]) were similar to those from Dose 1 to the unblinding date (0.9% and
0.1%, respectively [Table 12]). There were no adolescent deaths in the study .
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Page 68Table 17.Incidence Rates of at Least 1 Adverse Event From Unblinding Date to Data
Cutoff Date (02SEP2021) – Open -Label Follow -up Period – Subj ects Who
Originally Received BNT162b2 –Phase 2/3 Subjects 12 Through 15 Years
of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1107, TEb=3.3)
Adverse Event nc(%) IRd(95% CIe)
Any event 18(1.6) 5.4 (3.2, 8.5)
Relatedf4(0.4) 1.2 (0.3, 3.1)
Severe 3(0.3) 0.9 (0.2, 2.6)
Life-threatening 0 0.0 (0.0, 1.1)
Any serious adverse event 4(0.4) 1.2 (0.3, 3.1)
Relatedf0 0.0 (0.0, 1.1)
Severe 1(0.1) 0.3 (0.0, 1.7)
Life-threatening 0 0.0 (0.0, 1.1)
Any nonserious adverse event 14(1.3) 4.2 (2.3, 7.0)
Relatedf4(0.4) 1.2 (0.3, 3.1)
Severe 2(0.2) 0.6 (0.1, 2.2)
Life-threatening 0 0.0 (0.0, 1.1)
Any adverse event leading to withdrawal 0 0.0 (0.0, 1.1)
Relatedf0 0.0 (0.0, 1.1)
Severe 0 0.0 (0.0, 1.1)
Life-threatening 0 0.0 (0.0, 1.1)
Death 0 0.0 (0.0, 1.1)
a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. TE = total exposure time in 100 person -years across all subjects in the specified group. Exposure time for a subject is
the time from the unblinding date to data cutoff date. This value is the denominator for the incidence rate calculation.
c. n = Number of subjects reporting at least 1 occurrence of the specified event category. For "any event," n = number of
subjects reporting at least 1 occurrence of any event.
d. Incidence rate (IR) is calculated as number of subjects reporting the even t/total exposure time in 100 person -years
(PY) across all subjects in the specified group.
e. 2-sided CI based on Poisson distribution.
f.Assessed by the investigator as related to investigational product.
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2.5.5.2.3.2.2. Analysis of Adverse Events (Open -Label Follow -Up Period From the
Unblinding Date to the Data Cutoff Date –Original BNT162b2 Recipients )
Adverse Events by System Organ Class and Preferred Term (Open -Label Follow -Up
Period From the Unblinding Date to the Data Cutoff Date – Original BNT162b2
Recipients )
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Page 69From the unblinding date to the data cutoff date (open- label follow -up period), for adolescent
participants who originally received BNT162b2, the n umber of participants who reported at
least 1 AE was 18 (1.6%) (Table 17) compared to 95 (8.4%) from Dose 1 to the unblinding
date ( Table 12).
Overall, the rates in all SOCs after the unblinding date were lower or remained similar to
those in the blinded placebo- controlled period.
The frequency for the SOC of nervous s ystem disorders was 6 (0.5%), including the PTs
dizziness (2), headache (2), pres yncope (2), and syncope (1). The frequency for the SOC of
general disorders and administration site conditions was 4 (0.4%), with injection site pain (3)
as the most frequentl y reported PT.
Related Adverse Events –Open -Label Follow -Up Period From the Unblinding Date to the
Data Cutoff Date –Original BNT162b2 Participants
From the unblinding date to the data cutoff date (open- label follow -up period), for adolescent
participants who original ly received BNT162b2, the number of participants with AEs
assessed as related b y the investigator was 4 (0.4%). The frequencies of related AEs were
highest for reactogenicit y events and in the SOCs of general disorders and administration site
conditions (i njection site pain, fatigue, p yrexia, and pain) and nervous sy stem disorders
(headache and dizziness).
Severe o rLife-Threatening Adverse Events –Open -Label Follow -Up Period From the
Unblinding Date to the Data Cutoff Date –Original BNT162b2 Participants
From the unblinding date to the data cutoff date (open- label follow -up period), 3 (0.3%)
BNT162b2 participants experienced severe AEs. Two (2) participants experienced p yrexia
(general disorders and administration site conditions), a term consistent with reactogenicity .
There were no life -threatening AEs reported from the unblinding date to the data cutoff date
of 02 September 2021 (Table 17).
2.5.5.2.3.3. Blinded Place bo-Controlled and Open- Label Follow -Up Periods From Dose
1 to 6 Months After Dose 2 – Original BNT162b2 Recipients (Adverse Events)
2.5.5.2.3.3.1. Summary of Adverse Events (Blinded Placebo -Controlled and Open -Label
Follow -Up Periods From Dose 1 to 6 Months After Dose 2 –Original BNT162b2
Recipients )
There were 1113 adolescent participants who originally received BNT162b2 and had at least
6 months of follow -up time after Dose 2 including the blinded placebo- controlled and open -
label follow -up periods ( Table 18). There were 98 (8.8%) participants who reported at least 1
AE, and 34 (3.1%) participants reported at least 1 related AE. Severe AEs and SAEs were
reported b y 13 (1.2%) and 10 (0.9%) particip ants, respectivel y. There were no AEs leading to
withdrawal, and there were no deaths.
The frequencies of an y AEs and related AEs are 70 (6.3%) and 34 (3.1%) through 1 month
after Dose 2 compared with 35 (3.1%) and no related AEs from 1 month after Dose 2to
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Page 706months after Dose 2, respectively (Table 19). From Dose 1 t o 1 month after Dose 2, 3
(0.3%) adolescent participants reported SAEs. From 1 month to 6 months after Dose 2, 9
(0.8%) participants reported SAEs . Allof the SAEs were assessed b y the investigator as not
related to stud y intervention. There were no AEs leading to withdrawal, and there were no
deaths.
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Page 71Table 18. Number (%) of Subjects Reporting at Least 1 Ad verse Event From Dose 1
to 6 Months After Dose 2 – Subjects With at Least 6 Months of Follow- up
Time After Dose 2 –Phase 2/3 Subjects 12 Through 15 Years of Age
(Subjects Who Originally Received BNT162b2) – Safety Population
Vaccine Group (as Adm inistered)
BNT162b2 (30 μg)
(Na=1113)
Adverse Event nb(%) (95% CIc)
Any event 98(8.8) (7.2, 10.6)
Relatedd34(3.1) (2.1, 4.2)
Severe 13(1.2) (0.6, 2.0)
Life-threatening 0 (0.0, 0.3)
Any serious adverse event 10(0.9) (0.4, 1.6)
Relatedd0 (0.0, 0.3)
Severe 7(0.6) (0.3, 1.3)
Life-threatening 0 (0.0, 0.3)
Any nonserious adverse event 91(8.2) (6.6, 9.9)
Relatedd34(3.1) (2.1, 4.2)
Severe 6(0.5) (0.2, 1.2)
Life-threatening 0 (0.0, 0.3)
Any adverse event leading to withdrawal 0 (0.0, 0.3)
Relatedd0 (0.0, 0.3)
Severe 0 (0.0, 0.3)
Life-threatening 0 (0.0, 0.3)
Death 0 (0.0, 0.3)
a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. n = Number of subjects reporting at least 1 occurrence of the specified event category. For "any event," n = number of
subjects reporting at least 1 occurrence of any event.
c. Exact 2 -sided CI based on the Clopper and Pearson method.
d. Assessed by the investigator as related to investigational product.
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Page 72Table 19. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by Time Period – Subjects With at Least 6
Months of Follow -up Time After Dose 2 – Phase 2/3 Subjects 12 Through
15 Years of Age (Subjects Who Originally Received BNT162b2) –Safety
Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1113)
Dose 1 to 1 Month After Dose
21 Month After Dose 2 to 6 Months After
Dose 2
Adverse Event nb(%) nb(%)
Any event 70(6.3) 35(3.1)
Relatedc34(3.1) 0
Severe 6(0.5) 8(0.7)
Life-threatening 0 0
Any serious adverse event 3(0.3) 9(0.8)
Relatedc0 0
Severe 1(0.1) 7(0.6)
Life-threatening 0 0
Any nonserious adverse event 68(6.1) 28(2.5)
Relatedc34(3.1) 0
Severe 5(0.4) 1(0.1)
Life-threatening 0 0
Any adverse event leading to withdrawal 0 0
Relatedc0 0
Severe 0 0
Life-threatening 0 0
Death 0 0
a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. n = Number of subjects reporting at least 1 occurrence of the specified event category. For "any event," n = number of
subjects rep orting at least 1 occurrence of any event.
c. Assessed by the investigator as related to investigational product.
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Page 732.5.5.2.3.3.2. Analysis of Adverse Events (Blinded Placebo -Controlled and Open -Label
Follow -Up Periods From Dose 1 to 6 Months After Dose 2 –Original BNT162b2
Recipients )
Adverse Events by System Organ Class and Preferred Term (Blinded Placebo -
Controlled and Open -Label Follow -Up Periods From Dose 1 to 6 Months After Dose 2 –
Original BNT162b2 Recipients)
There were 98 (8.8%) adolescent participants who originall y received BNT162b2, had at
least 6 months of follow- up time after Dose 2, and reported AEs from Dose 1 to 6 months
after Dose 2 ( Table 20). Frequently reporte d AEs included reactogenicit y events in the
following SOCs:
general disorders and administration site conditions (16 [1.4%])
musculoskeletal and connective tissue disorders (8 [0.7%])
nervous s ystem disorders (16 [1.4%])
gastrointestinal disorders (16 [1.4 %])
AEs were reported b y 15 (1.3%) participants in the injury, poisoning, and procedural
complications SOC; 10 (0.9%) participants in the infections and infestations SOC, and
16(1.4%) participants in the psy chiatric disorders SOC.
When AEs are compared f rom Dose 1 to 1 month after Dose 2 and from 1 month after Dose
2 to 6 months after Dose 2, the frequencies of AEs by most SOCs were lower or were similar
with the additional follow -up time. The overall frequency of any AE for participants from
1 month afte r Dose 2 to 6 months after Dose 2 (35 [3.1%]) was less compared with the
frequency during 1 month follow up time after Dose 2 (70 [6.3%]) ( Table 21). Overall, AEs
repor ted after 1 month post Dose -2 reflect age -appropriate events consistent with the general
population.
All ly mphadenopathy events were reported from Dose 1 to 1 month after Dose 2, and none
were reported from 1 month to 6 months after Dose 2 ( Table 21).
AEs in the p yschiatric disorders SOC were reported in 7 (0.6%) participants from Dose 1 to
1 month after Dose 2 and in 11 (1.0%) participants from 1 month to 6 months after Dose 2.
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Page 74Table 20. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –
Subjects With at Least 6 Months of Follow -up Time After Dose 2 –Phase
2/3 Subjects 12 Thr ough 15 Years of Age (Subjects Who Originally
Received BNT162b2) –Safety Population
Vaccine Group (as
Administered)
BNT162b2 (30 μg)
(Na=1113)
System Organ Class
Preferred Termnb(%) (95% CIc)
Any event 98(8.8) (7.2, 10.6)
BLOOD AND LYMPHATIC SYSTEM DISORDERS 9 (0.8) (0.4, 1.5)
Lymphadenopathy 9 (0.8) (0.4, 1.5)
CONGENITAL, FAMILIAL AND GENETIC DISORDERS 1 (0.1) (0.0, 0.5)
Syringomyelia 1 (0.1) (0.0, 0.5)
EAR AND LABYRINTH DISORDERS 1 (0.1) (0.0, 0.5)
Ear pain 1 (0.1) (0.0, 0.5)
EYE DISORDERS 1 (0.1) (0.0, 0.5)
Eye pain 1 (0.1) (0.0, 0.5)
GASTROINTESTINAL DISORDERS 16 (1.4) (0.8, 2.3)
Nausea 6 (0.5) (0.2, 1.2)
Diarrhoea 3 (0.3) (0.1, 0.8)
Abdominal pain 2 (0.2) (0.0, 0.6)
Aphthous ulcer 2 (0.2) (0.0, 0.6)
Abdominal pain upper 1 (0.1) (0.0, 0.5)
Constipation 1 (0.1) (0.0, 0.5)
Gastritis 1 (0.1) (0.0, 0.5)
Lip swelling 1 (0.1) (0.0, 0.5)
Mouth swelling 1 (0.1) (0.0, 0.5)
Oral mucosal blistering 1 (0.1) (0.0, 0.5)
Rectal prolapse 1 (0.1) (0.0, 0.5)
Vomiting 1 (0.1) (0.0, 0.5)
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS 16 (1.4) (0.8, 2.3)
Fatigue 8 (0.7) (0.3, 1.4)
Injection site pain 8 (0.7) (0.3, 1.4)
Pyrexia 5 (0.4) (0.1, 1.0)
Chills 2 (0.2) (0.0, 0.6)
Injection site swelling 2 (0.2) (0.0, 0.6)
Nodule 1 (0.1) (0.0, 0.5)
Peripheral swelling 1 (0.1) (0.0, 0.5)
IMMUNE SYSTEM DISORDERS 1 (0.1) (0.0, 0.5)
Seasonal allergy 1 (0.1) (0.0, 0.5)
INFECTIONS AND INFESTATIONS 10 (0.9) (0.4, 1.6)
Ear infection 2 (0.2) (0.0, 0.6)
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Page 75Table 20. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –
Subjects With at Least 6 Months of Follow -up Time After Dose 2 –Phase
2/3 Subjects 12 Thr ough 15 Years of Age (Subjects Who Originally
Received BNT162b2) –Safety Population
Vaccine Group (as
Administered)
BNT162b2 (30 μg)
(Na=1113)
System Organ Class
Preferred Termnb(%) (95% CIc)
Anal abscess 1 (0.1) (0.0, 0.5)
Appendicitis 1 (0.1) (0.0, 0.5)
Body tinea 1 (0.1) (0.0, 0.5)
Otitis externa 1 (0.1) (0.0, 0.5)
Otitis media 1 (0.1) (0.0, 0.5)
Paronychia 1 (0.1) (0.0, 0.5)
Pilonidal cyst 1 (0.1) (0.0, 0.5)
Tinea capitis 1 (0.1) (0.0, 0.5)
Vulval abscess 1 (0.1) (0.0, 0.5)
Vulvovaginal mycotic infection 1 (0.1) (0.0, 0.5)
INJURY, POISONING AND PROCEDURAL COMPLICATIONS 15 (1.3) (0.8, 2.2)
Concussion 3 (0.3) (0.1, 0.8)
Hand fracture 2 (0.2) (0.0, 0.6)
Procedural pain 2 (0.2) (0.0, 0.6)
Accident 1 (0.1) (0.0, 0.5)
Bone contusion 1 (0.1) (0.0, 0.5)
Clavicle fracture 1 (0.1) (0.0, 0.5)
Contusion 1 (0.1) (0.0, 0.5)
Fall 1 (0.1) (0.0, 0.5)
Femur fracture 1 (0.1) (0.0, 0.5)
Ligament sprain 1 (0.1) (0.0, 0.5)
Meniscus injury 1 (0.1) (0.0, 0.5)
Muscle strain 1 (0.1) (0.0, 0.5)
Radius fracture 1 (0.1) (0.0, 0.5)
Upper limb fracture 1 (0.1) (0.0, 0.5)
INVESTIGATIONS 1 (0.1) (0.0, 0.5)
SARS -CoV -2 antibody test positive 1 (0.1) (0.0, 0.5)
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS 8 (0.7) (0.3, 1.4)
Myalgia 3 (0.3) (0.1, 0.8)
Arthralgia 2 (0.2) (0.0, 0.6)
Musculoskeletal chest pain 1 (0.1) (0.0, 0.5)
Osteochondrosis 1 (0.1) (0.0, 0.5)
Pain in extremity 1 (0.1) (0.0, 0.5)
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND
POLYPS)1 (0.1) (0.0, 0.5)
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Page 76Table 20. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –
Subjects With at Least 6 Months of Follow -up Time After Dose 2 –Phase
2/3 Subjects 12 Thr ough 15 Years of Age (Subjects Who Originally
Received BNT162b2) –Safety Population
Vaccine Group (as
Administered)
BNT162b2 (30 μg)
(Na=1113)
System Organ Class
Preferred Termnb(%) (95% CIc)
Hair follicle tumour benign 1 (0.1) (0.0, 0.5)
NERVOUS SYSTEM DISORDERS 16 (1.4) (0.8, 2.3)
Headache 5 (0.4) (0.1, 1.0)
Migraine 3 (0.3) (0.1, 0.8)
Presyncope 3 (0.3) (0.1, 0.8)
Dizziness 2 (0.2) (0.0, 0.6)
Syncope 2 (0.2) (0.0, 0.6)
Paraesthesia 1 (0.1) (0.0, 0.5)
PSYCHIATRIC DISORDERS 16 (1.4) (0.8, 2.3)
Depression 5 (0.4) (0.1, 1.0)
Anxiety 4 (0.4) (0.1, 0.9)
Suicidal ideation 3 (0.3) (0.1, 0.8)
Attention deficit hyperactivity disorder 2 (0.2) (0.0, 0.6)
Conversion disorder 1 (0.1) (0.0, 0.5)
Disorientation 1 (0.1) (0.0, 0.5)
Generalised anxiety disorder 1 (0.1) (0.0, 0.5)
Panic attack 1 (0.1) (0.0, 0.5)
Sleep terror 1 (0.1) (0.0, 0.5)
Tic 1 (0.1) (0.0, 0.5)
REPRODUCTIVE SYSTEM AND BREAST DISORDERS 1 (0.1) (0.0, 0.5)
Amenorrhoea 1 (0.1) (0.0, 0.5)
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS 3 (0.3) (0.1, 0.8)
Nasal congestion 2 (0.2) (0.0, 0.6)
Rhinorrhoea 2 (0.2) (0.0, 0.6)
Sneezing 1 (0.1) (0.0, 0.5)
SKIN AND SUBCUTANEOUS TISSUE DISORDERS 8 (0.7) (0.3, 1.4)
Acne 2 (0.2) (0.0, 0.6)
Dermatitis contact 2 (0.2) (0.0, 0.6)
Rash 2 (0.2) (0.0, 0.6)
Urticaria 2 (0.2) (0.0, 0.6)
SURGICAL AND MEDICAL PROCEDURES 1 (0.1) (0.0, 0.5)
Wisdom teeth removal 1 (0.1) (0.0, 0.5)
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Page 77Table 20. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –
Subjects With at Least 6 Months of Follow -up Time After Dose 2 –Phase
2/3 Subjects 12 Thr ough 15 Years of Age (Subjects Who Originally
Received BNT162b2) –Safety Population
Vaccine Group (as
Administered)
BNT162b2 (30 μg)
(Na=1113)
System Organ Class
Preferred Termnb(%) (95% CIc)
Note: MedDRA (v24.0) coding dictionary applied.
a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. n = Number of subjects reporting at least 1 occurrence of the specified event. For "any event," n = number of subjects
reporting at least 1 occurrence of any event.
c. Exact 2 -sided CI based on the Clopper and Pearson method.
PFIZER CONFIDENTIAL SDTM Creation: 05OCT2021 (18:29) Source Data: adae Table Generation: 03NOV2021
(10:31)
(Data Cutoff Date: 02SEP2021, Database Snapshot Date: 27SEP2021) Output File:
./nda2 unblinded/C4591001 S Peds/adae s130 all 6m1 ped6
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Page 78Table 21. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term and
Time Period –Subjects With at Least 6 Months of Follow -up Time After
Dose 2 –Phase 2/3 Subjects 12 Through 15 Years of Age (Subjects Who
Originally Received BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1113)
Dose 1 to 1 Month After
Dose 21 Month After Dose 2 to
6 Months After Dose 2
System Organ Class
Preferred Termnb(%) (95% CIc) nb(%) (95% CIc)
Any event 70(6.3) (4.9, 7.9) 35(3.1) (2.2, 4.3)
BLOOD AND LYMPHATIC SYSTEM DISORDERS 9 (0.8) (0.4, 1.5) 0 (0.0, 0.3)
Lymphadenopathy 9 (0.8) (0.4, 1.5) 0 (0.0, 0.3)
CONGENITAL, FAMILIAL AND GENETIC DISORDERS 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Syringomyelia 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
EAR AND LABYRINTH DISORDERS 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Ear pain 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
EYE DISORDERS 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Eye pain 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
GASTROINTESTINAL DISORDERS 14 (1.3) (0.7, 2.1) 3 (0.3) (0.1, 0.8)
Nausea 5 (0.4) (0.1, 1.0) 1 (0.1) (0.0, 0.5)
Diarrhoea 3 (0.3) (0.1, 0.8) 0 (0.0, 0.3)
Abdominal pain 2 (0.2) (0.0, 0.6) 1 (0.1) (0.0, 0.5)
Aphthous ulcer 1 (0.1) (0.0, 0.5) 1 (0.1) (0.0, 0.5)
Abdominal pain upper 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Constipation 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Gastritis 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Lip swelling 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Mouth swelling 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Oral mucosal blistering 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Rectal prolapse 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Vomiting 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
GENERAL DISORDERS AND ADMINISTRATION SITE
CONDITIONS16 (1.4) (0.8, 2.3) 0 (0.0, 0.3)
Fatigue 8 (0.7) (0.3, 1.4) 0 (0.0, 0.3)
Injection site pain 8 (0.7) (0.3, 1.4) 0 (0.0, 0.3)
Pyrexia 5 (0.4) (0.1, 1.0) 0 (0.0, 0.3)
Chills 2 (0.2) (0.0, 0.6) 0 (0.0, 0.3)
Injection site swelling 2 (0.2) (0.0, 0.6) 0 (0.0, 0.3)
Nodule 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Peripheral swelling 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
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Page 79Table 21. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term and
Time Period –Subjects With at Least 6 Months of Follow -up Time After
Dose 2 –Phase 2/3 Subjects 12 Through 15 Years of Age (Subjects Who
Originally Received BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1113)
Dose 1 to 1 Month After
Dose 21 Month After Dose 2 to
6 Months After Dose 2
System Organ Class
Preferred Termnb(%) (95% CIc) nb(%) (95% CIc)
IMMUNE SYSTEM DISORDERS 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Seasonal allergy 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
INFECTIONS AND INFESTATIONS 6 (0.5) (0.2, 1.2) 4 (0.4) (0.1, 0.9)
Ear infection 2 (0.2) (0.0, 0.6) 0 (0.0, 0.3)
Anal abscess 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Appendicitis 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Body tinea 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Otitis externa 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Otitis media 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Paronychia 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Pilonidal cyst 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Tinea capitis 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Vulval abscess 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Vulvovaginal mycotic infection 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
INJURY, POISONING AND PROCEDURAL COMPLICATIONS 9 (0.8) (0.4, 1.5) 6 (0.5) (0.2, 1.2)
Concussion 3 (0.3) (0.1, 0.8) 0 (0.0, 0.3)
Hand fracture 1 (0.1) (0.0, 0.5) 1 (0.1) (0.0, 0.5)
Procedural pain 0 (0.0, 0.3) 2 (0.2) (0.0, 0.6)
Accident 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Bone contusion 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Clavicle fracture 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Contusion 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Fall 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Femur fracture 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Ligament sprain 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Meniscus injury 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Muscle strain 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Radius fracture 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Upper limb fracture 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
INVESTIGATIONS 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
SARS -CoV -2 antibody test positive 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
MUSCULOSKELETAL AND CONNECTIVE TISSUE
DISORDERS8 (0.7) (0.3, 1.4) 0 (0.0, 0.3)
Myalgia 3 (0.3) (0.1, 0.8) 0 (0.0, 0.3)
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Page 80Table 21. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term and
Time Period –Subjects With at Least 6 Months of Follow -up Time After
Dose 2 –Phase 2/3 Subjects 12 Through 15 Years of Age (Subjects Who
Originally Received BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1113)
Dose 1 to 1 Month After
Dose 21 Month After Dose 2 to
6 Months After Dose 2
System Organ Class
Preferred Termnb(%) (95% CIc) nb(%) (95% CIc)
Arthralgia 2 (0.2) (0.0, 0.6) 0 (0.0, 0.3)
Musculoskeletal chest pain 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Osteochondrosis 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Pain in extremity 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED
(INCL CYSTS AND POLYPS)1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Hair follicle tumour benign 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
NERVOUS SYSTEM DISORDERS 11(1.0) (0.5, 1.8) 5 (0.4) (0.1, 1.0)
Headache 5 (0.4) (0.1, 1.0) 0 (0.0, 0.3)
Migraine 2 (0.2) (0.0, 0.6) 1 (0.1) (0.0, 0.5)
Presyncope 1 (0.1) (0.0, 0.5) 2 (0.2) (0.0, 0.6)
Dizziness 2 (0.2) (0.0, 0.6) 0 (0.0, 0.3)
Syncope 0 (0.0, 0.3) 2 (0.2) (0.0, 0.6)
Paraesthesia 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
PSYCHIATRIC DISORDERS 7 (0.6) (0.3, 1.3) 11 (1.0) (0.5, 1.8)
Depression 2 (0.2) (0.0, 0.6) 4 (0.4) (0.1, 0.9)
Anxiety 1 (0.1) (0.0, 0.5) 3 (0.3) (0.1, 0.8)
Suicidal ideation 0 (0.0, 0.3) 3 (0.3) (0.1, 0.8)
Attention deficit hyperactivity disorder 0 (0.0, 0.3) 2 (0.2) (0.0, 0.6)
Conversion disorder 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Disorientation 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Generalised anxiety disorder 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Panic attack 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Sleep terror 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Tic 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
REPRODUCTIVE SYSTEM AND BREAST DISORDERS 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Amenorrhoea 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
RESPIRATORY, THORACIC AND MEDIASTINAL
DISORDERS2 (0.2) (0.0, 0.6) 1 (0.1) (0.0, 0.5)
Nasal congestion 1 (0.1) (0.0, 0.5) 1 (0.1) (0.0, 0.5)
Rhinorrhoea 1 (0.1) (0.0, 0.5) 1 (0.1) (0.0, 0.5)
Sneezing 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
SKIN AND SUBCUTANEOUS TISSUE DISORDERS 6 (0.5) (0.2, 1.2) 2 (0.2) (0.0, 0.6)
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Page 81Table 21. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term and
Time Period –Subjects With at Least 6 Months of Follow -up Time After
Dose 2 –Phase 2/3 Subjects 12 Through 15 Years of Age (Subjects Who
Originally Received BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1113)
Dose 1 to 1 Month After
Dose 21 Month After Dose 2 to
6 Months After Dose 2
System Organ Class
Preferred Termnb(%) (95% CIc) nb(%) (95% CIc)
Acne 2 (0.2) (0.0, 0.6) 0 (0.0, 0.3)
Dermatitis contact 1 (0.1) (0.0, 0.5) 1 (0.1) (0.0, 0.5)
Rash 1 (0.1) (0.0, 0.5) 1 (0.1) (0.0, 0.5)
Urticaria 2 (0.2) (0.0, 0.6) 0 (0.0, 0.3)
SURGICAL AND MEDICAL PROCEDURES 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Wisdom teeth removal 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Note: MedDRA (v24.0) coding dictionary applied.
a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. n = Number of subjects reporting at least 1 occurrence of the specified event. For "any event," n = number of subjects
reporting at least 1 occurrence of any event.
c. Exact 2 -sided CI based on the Clopper and Pearson method.
PFIZER CONFIDENTIAL SDTM Creation: 05OCT2021 (18:29) Source Data: adae Table Generation: 03NOV2021
(10:21)
(Data Cutoff Date: 02SEP2021, Database Snapshot Date: 27SEP2021) Output File:
./nda2 unblinded/C4591001 S Peds/adae s132 6m1 ped6
Related Adverse Events –Blinded Placebo -Controlled and Open -Label Follow -Up Periods From
Dose 1 to 6 Months After Dose 2 – Original BNT162b2 Recipients
From Dose 1 to 6 months after Dose 2, 34 (3.1%) original BNT162b2 adolescent recipients
reported AEs assessed b y the investigator as related to study intervention. Most related AEs
were reactogenicit y events and in the SOC of general disorders and administration site
conditions, reported by 15 (1.3%) participants. Related events of l ymphadenopathy were
reported by7(0.6%) adolesce nts in the BNT162b2 group (refer to other significant AEs in
Section 2.5.5.2.7.1 ).
2.5.5.2.3.3.3. New Adverse Events Since EUA Snaps hot ( Blinded Placebo -Controlled
and Open -Label Follow -Up Periods From Dose 1 to 6 Months After Dose 2 –Original
BNT162b2 Recipients )
Summary of New Adverse Events Since EUA Snapshot ( Blinded Placebo -Controlled
and Open -Label Follow -Up Periods From Dose 1 to 6 Months After Dose 2 – Original
BNT162b2 Recipients )
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Page 82From the time after the EUA snapshot for adolescent BNT162b2 recipients who had at least
6 months of follow -up time after Dose 2 during the blinded placebo -controlled and open -
label follow -up periods, there were 36 (3.2%) participants who reported at least 1 AE, and
3 (0.3%) participants reported at least 1 related AE ( Table 22). Severe AEs an d SAEs were
reported b y 6(0.5%) and 7 (0.6%) participants, respectively . There were no AEs leading to
withdrawal, and there were no deaths.
When frequencies of new AEs for participants with at least 6 months of follow- up time are
examined by time since the second dose, the frequency of an y AEs and related AEs is
6 (0.5 %) and 3 (0. 3%) through 1 month after Dose 2 compared with 32 ( 2.9%) and no related
AEs from 1 month after Dose 2 to 6 months after Dose 2 ( Table 23). At 1 month af ter
Dose 2, no adolescent participants reported severe AEs or SAEs. From 1 month to 6 months
after Dose 2, the number of participants with severe AEs and total SAEs was 6 (0.5%) and 7
(0.6%), respectivel y. All of the new SAEs and all of the AEs reported from 1 month after
Dose 2 to 6 months after Dose 2 were assessed b y the investigator as not related to study
intervention.
Table 22.Number (%) of Subjects Reporting at Least 1 New Adverse Event After the
EUA Snapshot, From Dose 1 to 6 Months After Dose 2 – Subjects With at
Least 6 Months of Follow- up Time After Dose 2 – Phase 2/3 Subjects 12
Through 15 Years of Age (Subjects Who Originally Received BNT162b2) –
Safety Population
Vaccine Group (as Adm inistered)
BNT162b2 (30 μg)
(Na=1113)
Adverse Event nb(%) (95% CIc)
Any event 36(3.2) (2.3, 4.4)
Relatedd3(0.3) (0.1, 0.8)
Severe 6(0.5) (0.2, 1.2)
Life-threatening 0 (0.0, 0.3)
Any serious adverse event 7(0.6) (0.3, 1.3)
Relatedd0 (0.0, 0.3)
Severe 5(0.4) (0.1, 1.0)
Life-threatening 0 (0.0, 0.3)
Any nonserious adverse event 30(2.7) (1.8, 3.8)
Relatedd3(0.3) (0.1, 0.8)
Severe 1(0.1) (0.0, 0.5)
Life-threatening 0 (0.0, 0.3)
Any adverse event leading to withdrawal 0 (0.0, 0.3)
Relatedd0 (0.0, 0.3)
Severe 0 (0.0, 0.3)
Life-threatening 0 (0.0, 0.3)
Death 0 (0.0, 0.3)
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Page 83Table 22.Number (%) of Subjects Reporting at Least 1 New Adverse Event After the
EUA Snapshot, From Dose 1 to 6 Months After Dose 2 – Subjects With at
Least 6 Months of Follow- up Time After Dose 2 – Phase 2/3 Subjects 12
Through 15 Years of Age (Subjects Who Originally Received BNT162b2) –
Safety Population
Vaccine Group (as Adm inistered)
BNT162b2 (30 μg)
(Na=1113)
Adverse Event nb(%) (95% CIc)
Abbreviation: EUA = emergency use authorization.
Note: EUA snapshot 25Mar2021 with the cutoff date 13Mar2021.
a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. n = Number of subjects reporting at least 1 occurrence of the specified event category. For "any event," n = number of
subjects rep orting at least 1 occurrence of any event.
c. Exact 2 -sided CI based on the Clopper and Pearson method.
d. Assessed by the investigator as related to investigational product.
PFIZER CONFIDENTIAL SDTM Creation: 05OCT2021 (17:29) Source Data: adae Table Generation: 11NOV2021
(09:49)
(Data Cutoff Date: 02SEP2021, Database Snapshot Date: 27SEP2021) Output File:
./nda2 unblinded/C4591001 S Peds/adae s091 6m2 ped6
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Page 84Table 23.Number (%) of Subjects Reporting at Least 1 New Adverse Event After the
EUA Snapshot, From Dose 1 to 6 Months After Dose 2, by Time Period –
Subjects With at Least 6 Months of Follow -up Time After Dose 2 –Phase
2/3 Subjects 12 Through 15 Years of Age (Subjects Who Originally
Received BNT162b2) –Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1113)
Dose 1 to 1 Month After Dose
21 Month After Dose 2 to 6 Months After
Dose 2
Adverse Event nb(%) nb(%)
Any event 6(0.5) 32(2.9)
Relatedc3(0.3) 0
Severe 0 6(0.5)
Life-threatening 0 0
Any serious adverse event 0 7(0.6)
Relatedc0 0
Severe 0 5(0.4)
Life-threatening 0 0
Any nonserious adverse event 6(0.5) 26(2.3)
Relatedc3(0.3) 0
Severe 0 1(0.1)
Life-threatening 0 0
Any adverse event leading to withdrawal 0 0
Relatedc0 0
Severe 0 0
Life-threatening 0 0
Death 0 0
Abbreviation: EUA = emergency use authorization.
Note: EUA snapshot 25Mar2021 with the cutoff date 13Mar2021.
a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. n = Number of subjects reporting at least 1 occurrence of the specifi ed event category. For "any event," n = number of
subjects reporting at least 1 occurrence of any event.
c. Assessed by the investigator as related to investigational product.
PFIZER CONFIDENTIAL SDTM Creation: 05OCT2021 (17:29) Source Data: adae Tab le Generation: 11NOV2021
(09:45)
(Data Cutoff Date: 02SEP2021, Database Snapshot Date: 27SEP2021) Output File:
./nda2_unblinded/C4591001_S_Peds/adae_s093_6m2_ped6
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Page 85New Adverse Events Since EUA Snapshot by System Organ Class and Preferred Term
(Blinded Placebo -Controlled and Open -Label Follow -Up Periods From Dose 1 to 6
Months After Dose 2 – Original BNT162b2 Recipients)
Most of the new AEs reported after the EUA snapshot in adolescent participants with at least
6 months of follow -up time after D ose 2 were in the psychiatric disorders SOC (11 [1.0%])
(Table 24).
When AEs are compared from Dose 1 to1 month after Dose 2 and from 1 month after
Dose 2 to 6 months after Dose 2, AEs reported in the psy chiatric disorders SOC were
1(0.1%) and 10 (0.9%) p articipants, respectivel y (Table 25).All of the AE s in this SOC
were assessed by the investigator as not related to study intervention.
Table 24.Number (%) of Subjects Reporting at Least 1 New Adverse Event After the
EUA Snapshot, From Dose 1 to 6 Months After Dose 2, by System Organ
Class and Preferred Term – Subjects With at Least 6 Months of Follow -up
Time After Dose 2 –Phase 2/3 Subjects 12 Through 15 Years of Age
(Subjects Who Originally Received BNT162b2) – Safety Population
Vaccine Group (as
Administered)
BNT162b2 (30 μg)
(Na=1113)
System Organ Class
Preferred Termnb(%) (95% CIc)
Any event 36(3.2) (2.3, 4.4)
CONGENITAL, FAMILIAL AND GENETIC DISORDERS 1 (0.1) (0.0, 0.5)
Syringomyelia 1 (0.1) (0.0, 0.5)
EYE DISORDERS 1 (0.1) (0.0, 0.5)
Eye pain 1 (0.1) (0.0, 0.5)
GASTROINTESTINAL DISORDERS 3 (0.3) (0.1, 0.8)
Abdominal pain upper 1 (0.1) (0.0, 0.5)
Aphthous ulcer 1 (0.1) (0.0, 0.5)
Constipation 1 (0.1) (0.0, 0.5)
Nausea 1 (0.1) (0.0, 0.5)
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS 1 (0.1) (0.0, 0.5)
Chills 1 (0.1) (0.0, 0.5)
Fatigue 1 (0.1) (0.0, 0.5)
Injection site pain 1 (0.1) (0.0, 0.5)
Injection site swelling 1 (0.1) (0.0, 0.5)
Pyrexia 1 (0.1) (0.0, 0.5)
IMMUNE SYSTEM DISORDERS 1 (0.1) (0.0, 0.5)
Seasonal allergy 1 (0.1) (0.0, 0.5)
INFECTIONS AND INFESTATIONS 4 (0.4) (0.1, 0.9)
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Page 86Table 24.Number (%) of Subjects Reporting at Least 1 New Adverse Event After the
EUA Snapshot, From Dose 1 to 6 Months After Dose 2, by System Organ
Class and Preferred Term – Subjects With at Least 6 Months of Follow -up
Time After Dose 2 –Phase 2/3 Subjects 12 Through 15 Years of Age
(Subjects Who Originally Received BNT162b2) – Safety Population
Vaccine Group (as
Administered)
BNT162b2 (30 μg)
(Na=1113)
System Organ Class
Preferred Termnb(%) (95% CIc)
Anal abscess 1 (0.1) (0.0, 0.5)
Appendicitis 1 (0.1) (0.0, 0.5)
Paronychia 1 (0.1) (0.0, 0.5)
Pilonidal cyst 1 (0.1) (0.0, 0.5)
INJURY, POISONING AND PROCEDURAL COMPLICATIONS 6 (0.5) (0.2, 1.2)
Procedural pain 2 (0.2) (0.0, 0.6)
Bone contusion 1 (0.1) (0.0, 0.5)
Femur fracture 1 (0.1) (0.0, 0.5)
Hand fracture 1 (0.1) (0.0, 0.5)
Meniscus injury 1 (0.1) (0.0, 0.5)
Upper limb fracture 1 (0.1) (0.0, 0.5)
INVESTIGATIONS 1 (0.1) (0.0, 0.5)
SARS -CoV -2 antibody test positive 1 (0.1) (0.0, 0.5)
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS 1 (0.1) (0.0, 0.5)
Musculoskeletal chest pain 1 (0.1) (0.0, 0.5)
NERVOUS SYSTEM DISORDERS 4 (0.4) (0.1, 0.9)
Presyncope 2 (0.2) (0.0, 0.6)
Migraine 1 (0.1) (0.0, 0.5)
Syncope 1 (0.1) (0.0, 0.5)
PSYCHIATRIC DISORDERS 11 (1.0) (0.5, 1.8)
Anxiety 4 (0.4) (0.1, 0.9)
Depression 4 (0.4) (0.1, 0.9)
Attention deficit hyperactivity disorder 2 (0.2) (0.0, 0.6)
Suicidal ideation 2 (0.2) (0.0, 0.6)
Panic attack 1 (0.1) (0.0, 0.5)
REPRODUCTIVE SYSTEM AND BREAST DISORDERS 1 (0.1) (0.0, 0.5)
Amenorrhoea 1 (0.1) (0.0, 0.5)
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS 1 (0.1) (0.0, 0.5)
Nasal congestion 1 (0.1) (0.0, 0.5)
Rhinorrhoea 1 (0.1) (0.0, 0.5)
Sneezing 1 (0.1) (0.0, 0.5)
SKIN AND SUBCUTANEOUS TISSUE DISORDERS 2 (0.2) (0.0, 0.6)
Acne 1 (0.1) (0.0, 0.5)
Dermatitis contact 1 (0.1) (0.0, 0.5)
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Page 87Table 24.Number (%) of Subjects Reporting at Least 1 New Adverse Event After the
EUA Snapshot, From Dose 1 to 6 Months After Dose 2, by System Organ
Class and Preferred Term – Subjects With at Least 6 Months of Follow -up
Time After Dose 2 –Phase 2/3 Subjects 12 Through 15 Years of Age
(Subjects Who Originally Received BNT162b2) – Safety Population
Vaccine Group (as
Administered)
BNT162b2 (30 μg)
(Na=1113)
System Organ Class
Preferred Termnb(%) (95% CIc)
SURGICAL AND MEDICAL PROCEDURES 1 (0.1) (0.0, 0.5)
Wisdom teeth removal 1 (0.1) (0.0, 0.5)
Abbreviation: EUA = emergency use authorization.
Note: EUA snapshot 25Mar2021 with the cutoff date 13Mar2021.
Note: MedDRA (v24.0) coding dictionary applied.
a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. n = Number of subjec ts reporting at least 1 occurrence of the specified event. For "any event," n = number of subjects
reporting at least 1 occurrence of any event.
c. Exact 2 -sided CI based on the Clopper and Pearson method.
PFIZER CONFIDENTIAL SDTM Creation: 05OCT2021 (17:29) Source Data: adae Table Generation: 11NOV2021
(09:50)
(Data Cutoff Date: 02SEP2021, Database Snapshot Date: 27SEP2021) Output File:
./nda2 unblinded/C4591001 S Peds/adae s130 all 6m2 ped6
090177e198d7f76f\Approved\Approved On: 11-Dec-2021 18:37 (GMT)
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Page 88Table 25.Number (%) of Subjects Reporting at Least 1 New Adverse Event After the
EUA Snapshot, From Dose 1 to 6 Months After Dose 2, by System Organ
Class and Preferred Term and Time Period – Subjects With at Least 6
Months of Follow -up Time After Dose 2 – Phase 2/3 Subjects 12 Through
15 Years of Age (Subjects Who Originally Received BNT162b2) – Safety
Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1113)
Dose 1 to 1 Month After
Dose 21 Month After Dose 2 to 6
Months After Dose 2
System Organ Class
Preferred Termnb(%) (95% CIc) nb(%) (95% CIc)
Any event 6(0.5) (0.2, 1.2) 32(2.9) (2.0, 4.0)
CONGENITAL, FAMILIAL AND GENETIC DISORDERS 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Syringomyelia 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
EYE DISORDERS 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Eye pain 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
GASTROINTESTINAL DISORDERS 0 (0.0, 0.3) 3 (0.3) (0.1, 0.8)
Abdominal pain upper 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Aphthous ulcer 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Constipation 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Nausea 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
GENERAL DISORDERS AND ADMINISTRATION SITE
CONDITIONS1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Chills 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Fatigue 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Injection site pain 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Injection site swelling 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Pyrexia 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
IMMUNE SYSTEM DISORDERS 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Seasonal allergy 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
INFECTIONS AND INFESTATIONS 0 (0.0, 0.3) 4 (0.4) (0.1, 0.9)
Anal abscess 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Appendicitis 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Paronychia 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Pilonidal cyst 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
INJURY, POISONING AND PROCEDURAL
COMPLICATIONS0 (0.0, 0.3) 6 (0.5) (0.2, 1.2)
Procedural pain 0 (0.0, 0.3) 2 (0.2) (0.0, 0.6)
Bone contusion 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Femur fracture 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Hand fracture 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
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Page 89Table 25.Number (%) of Subjects Reporting at Least 1 New Adverse Event After the
EUA Snapshot, From Dose 1 to 6 Months After Dose 2, by System Organ
Class and Preferred Term and Time Period – Subjects With at Least 6
Months of Follow -up Time After Dose 2 – Phase 2/3 Subjects 12 Through
15 Years of Age (Subjects Who Originally Received BNT162b2) – Safety
Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1113)
Dose 1 to 1 Month After
Dose 21 Month After Dose 2 to 6
Months After Dose 2
System Organ Class
Preferred Termnb(%) (95% CIc) nb(%) (95% CIc)
Meniscus injury 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Upper limb fracture 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
INVESTIGATIONS 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
SARS -CoV -2 antibody test positive 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
MUSCULOSKELETAL AND CONNECTIVE TISSUE
DISORDERS1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Musculoskeletal chest pain 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
NERVOUS SYSTEM DISORDERS 0 (0.0, 0.3) 4 (0.4) (0.1, 0.9)
Presyncope 0 (0.0, 0.3) 2 (0.2) (0.0, 0.6)
Migraine 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Syncope 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
PSYCHIATRIC DISORDERS 1 (0.1) (0.0, 0.5) 10 (0.9) (0.4, 1.6)
Anxiety 1 (0.1) (0.0, 0.5) 3 (0.3) (0.1, 0.8)
Depression 0 (0.0, 0.3) 4 (0.4) (0.1, 0.9)
Attention deficit hyperactivity disorder 0 (0.0, 0.3) 2 (0.2) (0.0, 0.6)
Suicidal ideation 0 (0.0, 0.3) 2 (0.2) (0.0, 0.6)
Panic attack 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
REPRODUCTIVE SYSTEM AND BREAST DISORDERS 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Amenorrhoea 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
RESPIRATORY, THORACIC AND MEDIASTINAL
DISORDERS0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Nasal congestion 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Rhinorrhoea 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Sneezing 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
SKIN AND SUBCUTANEOUS TISSUE DISORDERS 1 (0.1) (0.0, 0.5) 1 (0.1) (0.0, 0.5)
Acne 1 (0.1) (0.0, 0.5) 0 (0.0, 0.3)
Dermatitis contact 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
SURGICAL AND MEDICAL PROCEDURES 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
Wisdom teeth removal 0 (0.0, 0.3) 1 (0.1) (0.0, 0.5)
090177e198d7f76f\Approved\Approved On: 11-Dec-2021 18:37 (GMT)
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Page 90Table 25.Number (%) of Subjects Reporting at Least 1 New Adverse Event After the
EUA Snapshot, From Dose 1 to 6 Months After Dose 2, by System Organ
Class and Preferred Term and Time Period – Subjects With at Least 6
Months of Follow -up Time After Dose 2 – Phase 2/3 Subjects 12 Through
15 Years of Age (Subjects Who Originally Received BNT162b2) – Safety
Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=1113)
Dose 1 to 1
…[truncated]