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 09 August 2021 CBER Information Request Regarding Sequencing Data
August 2021
090177e197c9be34\Approved\Approved On: 11-Aug-2021 19:14 (GMT)
FDA-CBER-2021-5683-0950306
BNT162b2
BLA STN 125742/0
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 2TABLE OF CONTENTS
1. INTRODUCTION ................................ ................................ ................................ ................. 3
2. CBER REQUESTS ................................ ................................ ................................ ................ 3
2.1. CBER Request 1 ................................ ................................ ................................ ........ 3
2.2. CBER Request 2 ................................ ................................ ................................ ........ 3
090177e197c9be34\Approved\Approved On: 11-Aug-2021 19:14 (GMT)
FDA-CBER-2021-5683-0950307
BNT162b2
BLA STN 125742/0
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 Information R equest (I R)
communicated from Captain Michael Smith ,PhD (CBER) to Elisa Harkins Tull (Pfizer I nc.)
via email on 09August 2021, with questions regarding Study C4591001 and sequencing
data.CBER has requested a response b y 12August 2021.
CBER’s comments/ requests in bold italics are followed b y the Sponsor’s responses below.
2.CBER REQUEST S
The review team has the below clinical questions for you regarding study
C4591001. Please respond as soon as possible and no later than Thursday, August 12,
2021.
2.1. CBER Request 1
One subject in the vaccine group, (Site No: 1252, Subject No: 12521010): 80- year- old
white, non -Hispanic male who received two doses of BNT162b2 (17 Aug 2020 and 08
September 2020), died from COVID pneumonia.
If available, please provide sequencing data for the virus isolated from this patient.
Response
Subject number 12521010 was not a confirmed COVID -19 case per protocol due to lack of
central lab or eligible local PCR test result . The diagnosis of COVID -19 pn eumonia was
based on a local COVID -19 test , which was not one of the approved assay sspecified in the
study . Additionally , the test was done locally , and hence the sponsor did not have access to
the specimen and is unable to perform the sequencing analy sis.
2.2.CBER Request 2
If there is available genomic sequencing data for any other COVID- 19 case, especially
those with fatal outcomes, and those from HIV positive subjects, please submit that
information.
Response
All available genomic sequencing data were included in SDTMdataset X B and ADaM
dataset ADXB of the eSUB package submitted on 07 June 2021 , which included cases from
the efficacy and safety analy sis cut- off date of 13 March 2021 . There was no sequencing data
available for HIV positive subjects. A total of 3 subjects who die d during the study had
090177e197c9be34\Approved\Approved On: 11-Aug-2021 19:14 (GMT)
FDA-CBER-2021-5683-0950308
BNT162b2
BLA STN 125742/0
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 4sequencing data (Table 1 ); 1 of these 3 subject shad sequencing done on swab taken after
unblinding.
090177e197c9be34\Approved\Approved On: 11-Aug-2021 19:14 (GMT)
FDA-CBER-2021-5683-0950309
BNT162b2
BLA STN 125742/0
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 5Table 1.eff.16.2.8.6.1 Listing of Subjects with Fatal Outcome and SARS -CoV -2 Varia nts for COVID -19 Occurrence After
Dose 1 –Dose 1 All -Available Efficacy Population
Subject
(Country/Region/Age
in Years/Sex)Vaccine Group
(as Randomized) Dose/Rel DayaStart Date of
First SymptomStop Date
of
Last
SymptomVisit 1
N-Binding
Assay/
Visit 1NAAT/
Visit 2 NAATSigns and
SymptomsSARS -CoV -
2 NAAT
Result
(Central
Lab/Local
Labb),
Swab Date,
SARS -CoV -
2 Lineage
C4591001 1027
10271191
(USA/NORTH
CAROLINA/68/F)Placebo Dose 2/103* 12JAN2021 13FEB2021 Neg/Neg/Neg Fever Pos/,
13JAN2021,
B.1.2
New or
increased
cough
New or
increased
shortness
of breath
Chills
New or
increased
muscle
pain
New loss
of taste or
smell
Vom iting
C4591001 1088
10881126
(USA/NORTH
CAROLINA/65/M)Placebo Dose 2/68 29NOV2020 01DEC2020 Neg/Neg/Neg New or
increased
coughPos/,
30NOV2020,
B.1.2
090177e197c9be34\Approved\Approved On: 11-Aug-2021 19:14 (GMT)
FDA-CBER-2021-5683-0950310
BNT162b2
BLA STN 125742/0
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 6Table 1.eff.16.2.8.6.1 Listing of Subjects with Fatal Outcome and SARS -CoV -2 Varia nts for COVID -19 Occurrence After
Dose 1 –Dose 1 All -Available Efficacy Population
Subject
(Country/Region/Age
in Years/Sex)Vaccine Group
(as Randomized) Dose/Rel DayaStart Date of
First SymptomStop Date
of
Last
SymptomVisit 1
N-Binding
Assay/
Visit 1NAAT/
Visit 2 NAATSigns and
SymptomsSARS -CoV -
2 NAAT
Result
(Central
Lab/Local
Labb),
Swab Date,
SARS -CoV -
2 Lineage
C4591001 1231
12315324 (ARG/58/F)Placebo Dose 2/99 25DEC2020 31JAN2021 Neg/Neg/Neg Fever Pos/,
26DEC2020,
B.1.1.291
New or
increased
cough
Chills
Abbreviations: ARG = Argentina; NAAT = nucleic acid amplification test; N -binding = SARS -CoV -2 nucleoprotein –binding; Neg = negative;
Pos = positive; SARS -CoV- 2 = severe acute respiratory syndrome coronavirus 2.
Note: HIV -positive subjects are included in this listing but not included in the analyses of the overall study objectives.
Note: * = COVID -19 occurrence after subject w as unblinded.
a. Relative Day (Rel Day) = date of first symptom -date of last dose before first symptom + 1.
b. SARS -CoV -2 NAAT results from the local lab are based on the Cepheid Xpert® Xpress SARS -CoV- 2 test, Roche cobas® SARS -CoV- 2 real -time RT -PCR
test (EUA200009/A001), or Abbott RealTime SARS -CoV -2 assay (EUA200023/A001) only.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsympt Table Generation: 09AUG2021 (15:41)
(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File: ./nda2_unblinded/C4591001_BLA_RR/adsy_l001_dth_cov_d1aai
090177e197c9be34\Approved\Approved On: 11-Aug-2021 19:14 (GMT)
FDA-CBER-2021-5683-0950311
Document Approval Record
Document Name:
!"! #!"! $%
Document Title:
!"! #!"! $%
Signed By: Date(GMT) Signing Capacity
&'()*
!"! + ,+ " -. /.
090177e197c9be34\Approved\Approved On: 11-Aug-2021 19:14 (GMT)
FDA-CBER-2021-5683-0950312