Document text
BNT162b2
BLA STN 125742/0
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 1BNT162b2 (COMIRNATY)
BLA STN 125742/0
Response to 13 August 2021 CBER Information Request Regarding Duration of
Follow-up in Study C4591001 (16+ Years of Age)
August 2021
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BNT162b2
BLA STN 125742/0
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 2TABLEOF CONTENTS
LIST OF TABLES.....................................................................................................................2
1.INTRODUCTION ................................ ................................ ................................ ................. 3
2.QUESTIONS ................................ ................................ ................................ ......................... 3
2.1. Question 1................................ ................................ ................................ ................. 3
2.2. Question 2................................ ................................ ................................ ................. 4
2.3. Question 3................................ ................................ ................................ ...............10
2.4. Question 4................................ ................................ ................................ ...............15
LIST OF TABLES
Table1.Blinded Follow -up Time After Dose 2 – Phase 2/3 Subjects ≥16 Years of
Age and With or Without Evidence of Infection Prior to 7 Day s After Dose
2 –Evaluable Efficacy (7 Days) Population ................................ ........................... 4
Table2.Disposition of All Randomized Subjects, by Age Group – Phase 2/3
Subjects ≥16 Years of Age Age Group: 16- 55 Years................................ .............5
Table3.Disposition of All Randomized Subjects, by Age Group – Phase 2/3
Subjects ≥16 Years of Age Age Group: >55 Years ................................ ................ 8
Table4.Follow-up Time After Dose 2, by Age Group – Phase 2/3 Subjects ≥16
Years of Age –Safety Population Age Group: 16 -55 Years................................ 11
Table5.Follow-up Time After Dose 2, by Age Group – Phase 2/3 Subjects ≥16
Years of Age –Safety Population Age Group: >55 Years ................................ ...12
Table6.Follow-up Time After Dose 2, by Age Group – Phase 2/3 Subjects ≥16
Years of Age and With or Without Evidence of Infection Prior to 7 Day s
After Dose 2 – Evaluable Efficacy (7 Days) Population Age Group: 16-55
Years................................ ................................ ................................ ..................... 13
Table7.Follow-up Time After Dose 2, by Age Group – Phase 2/3 Subjects
≥16Years of Age and With or Without Evidence of Infection Prior to
7Days After Dose 2 – Evaluable Efficacy (7 Days) Population Age Group:
>55 Years ................................ ................................ ................................ ..............14
Table8.Vaccine Efficacy –First COVID -19 Occurrence After Dose 1 – Blinded
Placebo-Controlled Follow -up Period – Subjects ≥16 Years of Age – Dose
1 All-Available Efficacy Population ................................ ................................ ....16
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M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 31.INTRODUCTION
Reference is made to BLA STN 125742/0 for the Pfizer -BioNTech COVID- 19 Vaccine for
active immunization to prevent COVID -19 caused by SARS-CoV-2 in individuals ≥16 y ears
of age.
The purpose of this document is to respond to CBER’s I nformation Request communicated
from Captain Michael Smith, PhD (CBER) via email on 13August 2021 .
Below, CBER’s comments/requests in bold italics are followed b y the Sponsor’s responses .
2.QUESTIONS
2.1.Question 1
Please complete the following table to describe follow -up time for the efficacy population.
Table. Blinded Follow -up Time after Dose 2, Phase 2/3 Participants 16 Years of Age
and Older, Evaluable Efficacy Population
Vaccine Group (as Rando mized)
BNT162b2
Na=21047
nb(%)Placebo
Na=21210
nb(%)Total
Na=42257
nb (%)
Evaluable efficacy (7 days) population
<2 Months
≥2 Months to <4 Months
≥4 Months to <6 Months
≥6 Months
Note: HIV -positive participants are notincluded in this summary because they are not included in the efficacy
analyses.
a. N = number of participants in the analys is population for the primary efficacy endpoints (evaluable
participants with and without evidence of prior infection). This va lue is the denominator for the percentage
calculations
b. n = Number of subjects with the specified characteristic.
Response
Blinded follow-uptime for participants 16 years of age and older in the evaluable efficacy
population (evaluable participants with and without evidence of prior infection) is
summarize d in Table1.
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Page 4Table1.Blinded Follow-up Time After Dose 2 – P hase 2/3 Subjects ≥16 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 Rando mized)
BNT162b2 (30 μg)
(Na=21047)
nb(%)Placebo
(Na=21210)
nb(%)Total
(Na=42257)
nb(%)
Subjects (%) w ith length of follow -up of:
Original blinded placebo -controlled follow -up
period
<2 Months 840 (4.0) 910 (4.3) 1750 (4.1)
≥2 Months to <4 months 7411 (35.2) 7851 (37.0) 15262 (36.1)
≥4 Months to <6 months 11031 (52.4) 11158 (52.6) 22189 (52.5)
≥6 Months 1765 (8.4) 1291 (6.1) 3056 (7.2)
Note: Human immunodeficiency virus (HIV) -positive subjects are not included in this summary.
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.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24 ) Source Data: adsl Table Generation:
13AUG2021 (16:37)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2_unblinded/C4591001_BLA_RR/adsl_fu_d2_p3_nohiv_ge16_eval
2.2.Question 2
Please provide the number of participants, by age cohort, who received placebo originally
and opted not to receive BNT162b2 after unblinding.
Response
The disposition tables below were included in the Interim CSR for Study C4591001 6 -Month
Update and are based on the data cutoff date of 13 March 2021.
Pfizer/BioNTech isnot able to determine the number of placebo participants who continued
in the study until the time of unblinding and “opted” (ie, chose) not to receive BNT162b2, as
differentiated from original placebo participants who had been unblinded but had not yet
received BNT162b2 for other reasons (eg, had not attended a visit after unblinding).
With that caveat, a scan be seen in Table2, among participants 16- 55 years of age, of the
13,132 participants originally randomized to placebo, 12,299 had been unblinded by the time
of data cutoff (under the heading “ Open-label follow -up period/Originall y randomized to
placebo”) . Among these 12,299 participants, 11,405 had received a first dose of BNT162b2
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Page 5at the time of data cutoff (labeledDose 3 in Table 2 ), leaving a remainder of 894 participants
originally randomized to placebo who had been unblinded but had not receivedBNT162b2 at
the time of data cutoff. Among these 894 participants , 284 withdrew before receiving
BNT162b2, and the other 610 either opted not to receive BNT162b2 or had not had the
opportunity to receive BNT162b2 at the time of data cutoff.
Among participants >55 years of age ( Table3), of the 8948 participants originall y
randomized to placebo, 8649 had been unblinded by the time of data cutoff. Among these
8649 participants, 8207 had received a first dose o f BNT162b2 at the time of data cutoff,
leaving a remainder of 442 participants originally randomized to placebo who had been
unblinded but had not received BNT162b2 at the time of data cutoff. Among these
442participant s, 213 withdrew before receiving BNT162b2, and the other 229either opted
not to receive BNT162b2 or had not had the opportunity to receive BNT162b2 at the time of
data cutoff.
Table2.Disposition of All Randomized Subjects, by Age Group –Phase 2/3
Subjects ≥16 Years of Age Age Group: 16-55 Years
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=13104)
nb(%)Placebo
(Na=13132)
nb(%)Total
(Na=26236)
nb(%)
Randomized 13104 (100.0) 13132 (100.0) 26236 (100.0)
Not vaccinated 31 (0.2) 32 (0.2) 63 (0.2)
Original blinded placebo -controlled follow -up period
Vaccinated 13073 (99.8) 13100 (99.8) 26173 (99.8)
Dose 1 13073 (99.8) 13100 (99.8) 26173 (99.8)
Dose 2 12802 (97.7) 12825 (97.7) 25627 (97.7)
Discontinued from original blinded placebo -controlled
vaccination periodc278 (2.1) 388 (3.0) 666 (2.5)
Reason for discontinuation
Lost to follow -up 132 (1.0) 128 (1.0) 260 (1.0)
Withdrawal by subject 81 (0.6) 117 (0.9) 198 (0.8)
Nolonger meets eligibility criteria 23 (0.2) 94 (0.7) 117 (0.4)
Adverse event 15 (0.1) 12 (0.1) 27 (0.1)
Pregnancy 6 (0.0) 6 (0.0) 12 (0.0)
Protocol deviation 2 (0.0) 6 (0.0) 8 (0.0)
Physician decision 3 (0.0) 4 (0.0) 7 (0.0)
Medication error without associated adverse event 2 (0.0) 1 (0.0) 3 (0.0)
Death 0 2 (0.0) 2 (0.0)
Withdrawal by parent/guardian 1 (0.0) 0 1 (0.0)
Other 13 (0.1) 18 (0.1) 31 (0.1)
Unblinded before 1 -month post –Dose 2 visit 175 (1.3) 182 (1.4) 357 (1.4)
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Page 6Table2.Disposition of All Randomized Subjects, by Age Group –Phase 2/3
Subjects ≥16 Years of Age Age Group: 16-55 Years
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=13104)
nb(%)Placebo
(Na=13132)
nb(%)Total
(Na=26236)
nb(%)
Completed 1 -month post –Dose 2 visit 12586 (96.0) 12555 (95.6) 25141 (95.8)
Withdrawn from the study 259 (2.0) 349 (2.7) 608 (2.3)
Withdrawn after Dose 1 and before Dose 2 138 (1.1) 155 (1.2) 293 (1.1)
Withdrawn after Dose 2 and before 1 -month post –Dose 2
visit85 (0.6) 104 (0.8) 189 (0.7)
Withdrawn after 1 -month post –Dose 2 visit 36 (0.3) 90 (0.7) 126 (0.5)
Reason for withdrawal from the study
Lost to follow -up 150 (1.1) 160 (1.2) 310 (1.2)
Withdrawal by subject 88 (0.7) 147 (1.1) 235 (0.9)
Protocol deviation 3 (0.0) 20 (0.2) 23 (0.1)
Adverse event 6 (0.0) 3 (0.0) 9 (0.0)
Death 3 (0.0) 5 (0.0) 8 (0.0)
Physician decision 2 (0.0) 3 (0.0) 5 (0.0)
No longer meets eligibility criteria 1 (0.0) 2 (0.0) 3 (0.0)
Pregnancy 0 1 (0.0) 1 (0.0)
Medication error without associated adverse event 1 (0.0) 0 1 (0.0)
Withdrawal by parent/guardian 1 (0.0) 0 1 (0.0)
Other 4 (0.0) 8 (0.1) 12 (0.0)
Open-label follow -up period
Originally randomized to BNT162b2 11858 (90.5)
Received Dose 2/unplanned dose 61 (0.5)
Completed 1 -month post –Dose 2 visit 141 (1.1)
Completed 6 -month post –Dose 2 visit 3341 (25.5)
Withdrawn from the study 58 (0.4)
Withdrawn before 6 -month post –Dose 2 visit 56 (0.4)
Withdrawn after 6-month post –Dose 2 visit 2 (0.0)
Reason for withdrawal from the study
Withdrawal by subject 32 (0.2)
Protocol deviation 17 (0.1)
Lost to follow -up 3 (0.0)
Physician decision 2 (0.0)
Adverse event 1 (0.0)
No longer meets eligibility criteria 1 (0.0)
Other 2 (0.0)
Originally randomized to placebo 12299 (93.7)
Withdrawn from the study after unblinding and before
Dose 3284 (2.2)
Received Dose 3 (first dose of BNT162b2 [30 μg]) 11405 (86.8)
Received Dose 4 (second dose of BNT162b2 [30 μg]) 8586 (65.4)
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PFIZER CONFIDENTIAL
Page 7Table2.Disposition of All Randomized Subjects, by Age Group –Phase 2/3
Subjects ≥16 Years of Age Age Group: 16-55 Years
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=13104)
nb(%)Placebo
(Na=13132)
nb(%)Total
(Na=26236)
nb(%)
Discontinued from open -label vaccination periodd16 (0.1)
Reason for discontinuation from open -label vaccination
period
Withdrawal by subject 5 (0.0)
Pregnancy 4 (0.0)
Adverse event 3 (0.0)
Protocol deviation 3 (0.0)
Lost to follow -up 1(0.0)
Completed 1 -month post –Dose 4 visit 3424 (26.1)
Withdrawn from the study 8 (0.1)
Withdrawn after Dose 3 and before Dose 4 6 (0.0)
Withdrawn after Dose 4 and before 1 -month post –Dose 4
visit2 (0.0)
Withdrawn after 1 -month post –Dose 4 visit 0
Reason for withdrawal from the study
Withdrawal by subject 7 (0.1)
Protocol deviation 1 (0.0)
Note: Human immunodeficiency virus (HIV) -positive subjects are included in this summary but analyzed and reported
separately.
Note: Subjects randomized but did not sign informed consent or had a significant quality event due to lack of PI oversight
are not included in any analysis population.
Note: Because of a dosing error, Subjects C4591001 1081 10811053, C4591001 1088 10881077, C4591001 1177
11771089 and C4591001 1231 12311057 received an additional dose of BNT162b2 (30 µg) at an unscheduled visit after
receiving 1 dose of BNT162b2 (30 µg) and 1 dose of placebo.
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 spec ified characteristic.
c. Original blinded placebo -controlled vaccination period is defined as the time period from Dose 1 to 1 month post –
Dose 2.
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]).
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (19:20) Source Data: adds Table Generation: 27MAR2021
(16:41)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output
File: ./nda2_unblinded/ C4591001_BLA/adds_s002_age_p3_rand
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PFIZER CONFIDENTIAL
Page 8Table3.Disposition of All Randomized Subjects, by Age Group –Phase 2/3
Subjects ≥16 Years of Age Age Group: >55 Years
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=8981)
nb(%)Placebo
(Na=8948)
nb(%)Total
(Na=17929)
nb(%)
Randomized 8981 (100.0) 8948 (100.0) 17929 (100.0)
Not vaccinated 24 (0.3) 18 (0.2) 42 (0.2)
Original blinded placebo -controlled follow -up period
Vaccinated 8957 (99.7) 8930 (99.8) 17887 (99.8)
Dose 1 8957 (99.7) 8930 (99.8) 17887 (99.8)
Dose 2 8873 (98.8) 8825 (98.6) 17698 (98.7)
Discontinued from original blinded placebo-controlled
vaccination periodc74 (0.8) 140 (1.6) 214 (1.2)
Reason for discontinuation
Withdrawal by subject 28 (0.3) 64 (0.7) 92 (0.5)
Lost to follow -up 19 (0.2) 25 (0.3) 44 (0.2)
No longer meets eligibility criteria 3 (0.0) 26 (0.3) 29 (0.2)
Adverse event 12 (0.1) 14 (0.2) 26 (0.1)
Physician decision 2 (0.0) 4 (0.0) 6 (0.0)
Death 3 (0.0) 2 (0.0) 5 (0.0)
Protocol deviation 1 (0.0) 2 (0.0) 3 (0.0)
Medication error without associated adverse event 1 (0.0) 1 (0.0) 2 (0.0)
Other 5 (0.1) 2 (0.0) 7 (0.0)
Unblinded before 1 -month post –Dose 2 visit 78 (0.9) 58 (0.6) 136 (0.8)
Completed 1 -month post –Dose 2 visit 8796 (97.9) 8738 (97.7) 17534 (97.8)
Withdrawn from the study 84 (0.9) 135 (1.5) 219 (1.2)
Withdrawn after Dose 1 and before Dose 2 38 (0.4) 56 (0.6) 94 (0.5)
Withdrawn after Dose 2 and before 1 -month post –Dose 2
visit15 (0.2) 35 (0.4) 50 (0.3)
Withdrawn after 1 -month post –Dose 2 visit 31 (0.3) 44 (0.5) 75 (0.4)
Reason for withdrawal from the study
Withdrawal by subject 34 (0.4) 79 (0.9) 113 (0.6)
Lost to follow -up 24 (0.3) 31 (0.3) 55 (0.3)
Death 13 (0.1) 10 (0.1) 23 (0.1)
Protocol deviation 8 (0.1) 4 (0.0) 12 (0.1)
Adverse event 3 (0.0) 5 (0.1) 8 (0.0)
Physician decision 1 (0.0) 3 (0.0) 4 (0.0)
No longer meets eligibility criteria 0 2 (0.0) 2 (0.0)
Other 1 (0.0) 1 (0.0) 2 (0.0)
Open-label follow -up period
Originally randomized to BNT162b2 8546 (95.2)
Received Dose 2/unplanned dose 26 (0.3)
Completed 1 -month post –Dose 2 visit 69 (0.8)
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PFIZER CONFIDENTIAL
Page 9Table3.Disposition of All Randomized Subjects, by Age Group –Phase 2/3
Subjects ≥16 Years of Age Age Group: >55 Years
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=8981)
nb(%)Placebo
(Na=8948)
nb(%)Total
(Na=17929)
nb(%)
Completed 6 -month post –Dose 2 visit 3073 (34.2)
Withdrawn from the study 47 (0.5)
Withdrawn before 6 -month post –Dose 2 visit 47 (0.5)
Withdrawn after 6 -month post –Dose 2 visit 0
Reason for withdrawal from the study
Withdrawal by subject 24 (0.3)
Protocol deviation 18 (0.2)
Death 3 (0.0)
Lost to follow -up 1 (0.0)
Other 1 (0.0)
Originally randomized to placebo 8649 (96.7)
Withdrawn from the study after unblinding and before Dose
3213 (2.4)
Received Dose 3 (first dose of BNT162b2 [30 μg]) 8207 (91.7)
Received Dose 4 (second dose of BNT162b2 [30 μg]) 7400 (82.7)
Discontinued from open -label vaccination periodd8 (0.1)
Reason for discontinuation from open -label vaccination
period
Protocol deviation 3 (0.0)
Adverse event 2 (0.0)
Death 2 (0.0)
Lost to follow -up 1 (0.0)
Completed 1 -month post –Dose 4 visit 3785 (42.3)
Withdrawn from the study 6 (0.1)
Withdrawn after Dose 3 and before Dose 4 5 (0.1)
Withdrawn after Dose 4 and before 1 -month post –Dose 4
visit0
Withdrawn after 1 -month post –Dose 4 visit 1 (0.0)
Reason for withdrawal from the study
Death 2 (0.0)
Protocol deviation 2 (0.0)
Adverse event 1 (0.0)
Lost to follow -up 1 (0.0)
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Page 10Table3.Disposition of All Randomized Subjects, by Age Group –Phase 2/3
Subjects ≥16 Years of Age Age Group: >55 Years
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=8981)
nb(%)Placebo
(Na=8948)
nb(%)Total
(Na=17929)
nb(%)
Note: Human immunodeficiency virus (HIV) -positive subjects are included in this summary but analyzed and reported
separately.
Note: Subjects randomized but did not sign informed consent or had a significant quality event due to lack of PI oversight
are not included in any analysis population.
Note: Because of a dosing error, Subjects C4591001 1081 10811053, C4591001 1088 10881077, C4591001 1177
11771089 and C4591001 1231 12311057 received an additional dose of BNT162b2 (30 µg) at an unscheduled visit after
receiving 1 dose of BNT162b2 (30 µg) and 1 dose of placebo.
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 spec ified characteristic.
c. Original blinded placebo -controlled vaccination period is defined as the time period from Dose 1 to 1 month post –
Dose 2.
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]).
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (19:20) Source Data: adds Table Generation: 27MAR2021
(16:41)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output
File: ./nda2_unblinded/ C4591001_BLA/adds_s002_age_p3_rand
2.3.Question 3
Please provide a breakdown of the subjects by age cohorts (young adults and older adults)
who have ≥6 months of follow -up from Dose 2 to the earlier of discontinuation or the
cutoff date, separately forthe Safety and Evaluable Efficacy Populations. Please also
provide a breakdown of these subjects, number of doses received and time of follow up
after last dose.
Response
Follow-up time afterDose 2 by age cohorts for the Safety Population was summarized in the
Interim CSR for Study C4591001 6 -Month Update and is provided again below. In terms of
total follow -up time (blinded placebo -controlled follow -up period, plus open-label follow -up
from unblinding to the earlier of discontinuation or the cutoff date ), in the original
BNT162b2 group, 6666 p articipants 16-55 years of age ( Table4) and 5340 participants
>55years of age ( Table5) had ≥6 months of follow -up after Dose 2.
A similar summary of follow -up after Dose 2 is provided below for the evaluable efficacy
population .In terms of total follow -up time,in the original BNT162b2 group,
6531participants 16 -55 years ofage (Table6) and 5232 participants >55 years of age
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Page 11(Table7) had ≥6months of follow -up from Dose 2 to the earlier of discontinuation or the
cutoff date.
Table4.Follow-up Time After Dose 2, by Age Group – Phase 2/3 Subjects ≥16
Years of Age –Safety Population Age Group: 16- 55 Years
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=13069)
nb(%)Placebo
(Na=13095)
nb(%)Total
(Na=26164)
nb(%)
Subjects (%) with length of follow -up of:
Original blinded placebo -controlled follow -up period
<2 Months 917 (7.0) 962 (7.3) 1879 (7.2)
≥2 Months to <4 months 4448 (34.0) 4726 (36.1) 9174 (35.1)
≥4 Months to <6 months 6343 (48.5) 6327 (48.3) 12670 (48.4)
≥6 Months 1361 (10.4) 1080 (8.2) 2441 (9.3)
Total exposure from Dose 2 to cutoff date
<2 Months 305 (2.3)
≥2 Months to <4 months 552 (4.2)
≥4 Months to <6 months 5546 (42.4)
≥6 Months 6666 (51.0)
Note: Human immunodeficiency virus (HIV) -positive subjects are included in this summary but analyzed and reported
separately.
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.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24 ) Source Data: adsl Table Generation: 27MAR2021
(01:37)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output
File: ./nda2_unblinded/C4591001_BLA/adsl_fu_d2_age_p3_saf
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Page 12Table5.Follow-up Time After Dose 2, by Age Group – Phase 2/3 Subjects ≥16
Years of Age – Safety Population Age Group: >55 Years
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=8957)
nb(%)Placebo
(Na=8926)
nb(%)Total
(Na=17883)
nb(%)
Subjects (%) with length of follow -up of:
Original blinded placebo -controlled follow -up period
<2 Months 334 (3.7) 369 (4.1) 703 (3.9)
≥2 Months to <4 months 3296 (36.8) 3344 (37.5) 6640 (37.1)
≥4 Months to <6 months 4910 (54.8) 4989 (55.9) 9899 (55.4)
≥6 Months 417 (4.7) 224 (2.5) 641 (3.6)
Total exposure from Dose 2 to cutoff date
<2 Months 85 (0.9)
≥2 Months to <4 months 127 (1.4)
≥4 Months to <6 months 3405 (38.0)
≥6 Months 5340 (59.6)
Note: Human immunodeficiency virus (HIV) -positive subjects are included in this summary but analyzed and reported
separately.
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.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation: 27MAR2021
(01:37)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output
File: ./nda2_u nblinded/C4591001_BLA/adsl_fu_d2_age_p3_saf
090177e197d2750a\Approved\Approved On: 16-Aug-2021 18:27 (GMT)
FDA-CBER-2021-5683-0950328
BNT162b2
BLA STN 125742/0
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 13Table6.Follow-up Time After Dose 2, by Age Group – Phase 2/3 Subjects ≥16
Years of Age and With or Without Evidence of Infection Prior to 7 Days
After Dose 2 –Evaluable Efficacy (7 Days) Population
Age Group: 16- 55 Years
Vaccine Group (as Rando mized)
BNT162b2 (30 μg)
(Na=12424)
nb(%)Placebo
(Na=12552)
nb(%)Total
(Na=24976)
nb(%)
Subjects (%) w ith length of follow -up of:
Original blinded placebo-controlled follow -up
period
<2 Months 612 (4.9) 661 (5.3) 1273 (5.1)
≥2 Months to <4 months 4258 (34.3) 4592 (36.6) 8850 (35.4)
≥4 Months to <6 months 6201 (49.9) 6224 (49.6) 12425 (49.7)
≥6 Months 1353 (10.9) 1075 (8.6) 2428 (9.7)
Total exposure from Dose 2 to cutoff date
<2 Months 54 (0.4)
≥2 Months to <4 months 518 (4.2)
≥4 Months to <6 months 5321 (42.8)
≥6 Months 6531 (52.6)
Note: Human immunodeficiency virus (HIV)-positive subjects are not included in this summary.
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 characteris tic.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation:
13AUG2021 (16:50)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:
./nda2_unblinded/C4591001_BLA_RR/adsl_fu_d2p3_nohiv_ge16_age_eval
090177e197d2750a\Approved\Approved On: 16-Aug-2021 18:27 (GMT)
FDA-CBER-2021-5683-0950329
BNT162b2
BLA STN 125742/0
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 14Table7.Follow-up Time After Dose 2, by Age Group – Phase 2/3 Subjects
≥16Years of Age and With or Without Evidence of Infection Prior to
7Days After Dose 2 – Evaluable Efficacy (7 Days) Population
Age Group: >55 Years
BNT162b2 (30 μg)
(Na=8623)
nb(%)Placebo
(Na=8658)
nb(%)Total
(Na=17281)
nb(%)
Subjects (%) w ith length of follow -up of:
Original blinded placebo -controlled follow -up
period
<2 Months 228 (2.6) 249 (2.9) 477 (2.8)
≥2 Months to <4 months 3153 (36.6) 3259 (37.6) 6412 (37.1)
≥4 Months to <6 months 4830 (56.0) 4934 (57.0) 9764 (56.5)
≥6 Months 412 (4.8) 216 (2.5) 628 (3.6)
Total exposure from Dose 2 to cutoff date
<2 Months 12 (0.1)
≥2 Months to <4 months 101 (1.2)
≥4 Months to <6 months 3278 (38.0)
≥6 Months 5232 (60.7)
Note: Human immunodeficiency virus (HIV) -positive subjects are not included in this summary.
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.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation:
13AUG2021 (16:50)
(Cutoff Date: 13MAR2021, S napshot Date: 25MAR2021) Output File:
./nda2_unblinded/C4591001_BLA_RR/adsl_fu_d2p3_nohiv_ge16_age_eval
090177e197d2750a\Approved\Approved On: 16-Aug-2021 18:27 (GMT)
FDA-CBER-2021-5683-0950330
BNT162b2
BLA STN 125742/0
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 152.4.Question 4
Please complete the following table to describe the updated VE at later time points periods,
to supplement Table O provided with the VE shell tables in STN 125742.0.32.
Response
Table8has been updated to describe VE at later time points.Table O. Updated Vaccine Eff icacy after Dose 1, Dose 1 All -Available Efficacy
Population
Efficacy Endpoin t SubgroupBNT162b2
(Na=21909)
Cases
n1b
Surveillance
Timec
(n2d)Placebo
(Na=21908)
Cases
n1b
Surveillance
Timec
(n2d)Vaccine
Efficacy %
(95% CI)e
First COVID -19 occurrence aft er
Dose 1128
8.155 ( 2138 5)998
7.874 ( 2131 5)87.6
(85.1, 89.8)
After Dose 1 to before Dose 243
1.273 ( 2138 5)98
1.266 ( 2131 5)56.4
(37.0, 70.3)
Dose 2 to 7 days af ter Dose 23
0.403 ( 2104 9)30
0.401 ( 2095 2)90
(68.0, 98.1)
≥7 Day s after Dose 282
6.479 ( 2101 9)870
6.207 ( 2090 1)91
(88.7, 92.9)
≥7 Day s after Dose 2 to<2 Months
after Dose 2
≥2 Mont hs after Dose 2 to 4
Months after Dose 2
≥4 Mont hs after Dose 2
Abbrevi ation: VE = va ccine effi cacy.
aN = number of subjects in the specified group.
bn1 = Number of subject s meeting t he endpoi nt definition.
cTotal surveill ance time in 1 000 person -years for the given endpoint across all
subjects within each group at risk for the endpoint. Time period for COVID -19
case accrua l is from Dose 1 to the end of the surveillance period.
dn2 = Number of subject s at risk for t he endpoi nt.
eConfi dence interva l (CI) for V E is derived based on the Clopper and Pearson
method adjusted for surveillance t ime.
090177e197d2750a\Approved\Approved On: 16-Aug-2021 18:27 (GMT)
FDA-CBER-2021-5683-0950331
BNT162b2
BLA STN 125742/0
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 16Table8.Vaccine Efficacy – First COVID -19 Occurrence After Dose 1 –Blinded Placebo- Controlled Follow -up
Period–Subjects ≥16 Years of Age – Dose 1 All-Available Efficacy Population
Vaccine Group (as Rando mized)
BNT162b2 (30 μg)
(Na=21909)Placebo
(Na=21908)
Efficacy Endpoint
Subgroup n1bSurveillance
Timec(n2d)n1bSurveillance
Timec(n2d)VE (%) (95% CIe)
First COVID -19 occurrence after Dose 1 128 8.155 (21385) 998 7.874 (21315) 87.6 (85.1, 89.8)
After Dose 1 to before Dose 2 43 1.273 (21385) 98 1.266 (21315) 56.4 (37.0, 70.3)
After Dose 1 to <11 days after Dose 1 38 0.643 (21385) 46 0.641 (21315) 17.6 (-29.4, 47.9)
≥11 Days after Dose 1 to before Dose 2 5 0.630 (21282) 52 0.625 (21254) 90.5 (76.3, 97.0)
Dose 2 to 7 days after Dose 2 3 0.403 (21049) 30 0.401 (20952) 90.0 (68.0, 98.1)
≥7 Days after Dose 2 82 6.479 (21019) 870 6.207 (20901) 91.0 (88.7, 92.9)
≥7 days after Dose 2 to <2 Months after Dose 2 12 2.786 (21019) 296 2.750 (20901) 96.0 (92.9, 98.0)
≥2 Months after Dose 2 to <4 Months after Dose 2 46 2.665 (20160) 446 2.564 (19720) 90.1 (86.5, 92.8)
≥4 Months after Dose 2 24 1.028 (12624) 128 0.893 (11760) 83.7 (74.7, 89.9)
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 w ithin each group at risk for the endpoint. Time
period for COVID -19 case accrual is from Dose 1 to the end of the surveillance period.
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.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (19:19) Source Data: adc19ef Table Generation: 06AUG2021 (08:58)
(Cutoff Date: 13MAR2021, Snapsh ot Date: 25MAR2021) Output File:
./nda2 unblinded/C4591001 BLA Efficacy v2/adc19ef ve cov pd1 aai
090177e197d2750a\Approved\Approved On: 16-Aug-2021 18:27 (GMT)
FDA-CBER-2021-5683-0950332
Document Approval Record
Document Name:
Document Title:
Signed By: Date(GMT) Signing Capacity
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090177e197d2750a\Approved\Approved On: 16-Aug-2021 18:27 (GMT)
FDA-CBER-2021-5683-0950333