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COVID -19 Vaccine (BNT162, PF -07302048)
BB-IND 19736
M 1.12.4 Requests for Comments and Advice
PFIZER CONFIDENTIAL
Page 1COVID -19 Vaccine (BNT162, PF- 07302048)
IND 19736
Request for Comments and Advice Regarding Adolescent (12- 15 Years of Age)
Supplemental BLA Propos ed Clinical Package
August 2021
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COVID -19 Vaccine (BNT162, PF -07302048)
BB-IND 19736
M 1.12.4 Requests for Comments and Advice
PFIZER CONFIDENTIAL
Page 21.INTRODUCTION
Reference is made to Investigational New Drug (IND) 19736 for COVID- 19mRNA Vaccine
(BNT162; PF -07302048), which Pfizer and BioNTech are developing for the indication of
active immunization to prevent COVID -19 caused by SARS -CoV -2. The IND was effective
on 29 April 2020.
Reference is also made to Biologics License Application (BLA )STN 125742/0 for
COVID -19 mRNA Vaccine (COMIRNATY) for active immunization to prevent COVID-19
caused b y SARS -CoV -2 in individuals ≥16years of age , currentl y under review by CBER.
Individuals 12 -15 years of age are currently eligible for vaccination with the COVID -19
mRNA Vaccine (Pfizer -BioNTech COVID -19 Vaccine) under Emergency Use Authorization
(EUA 27034) which wasauthorized by CBER on 10 May 2021.
Pfizer/BioNTech are planning for a supplemental BLA (sBLA )fortheCOVID -19 mRNA
Vaccine for the adolescent (12 -15 years of age) group in pivotal Phase 1/2/3 Study
C4591001. The present submission provides a Request for Comments and Advice regarding
the propos ed scope of this sBLA.
Pfizer /BioNTech respectfully request CBER’s feedback by 17August 2021.
2.QUESTIONS FOR CBER
2.1.Question 1
Does CBER agree with the proposed clinical safety analyses inthe planned sBLA to
support an indication for individuals ≥ 12 years of age?
Pfizer /BioNTech propos e the same approach use dfor BLA 125742 that included data from
approximately 44,000 participants ≥16yearsof age ,among whom approximately 12,000 had
at least 6 months of follow- up after Dose 2 of BNT162b2. The sBLA would include s afety
data forall of the approximately 2200 participants 12-15 years of age enrolled in Study
C4591001, among whom approximately 1100 would have at least 6months of follow -up
after Dose 2 of BNT162b2. P articipants have been unblinded to treatment assignment asthey
have become eligible forvaccin ation under EUA; therefore safet y data would be presented
from blinded placebo -controlled and open -label periods as follows :
a.Blinded placebo -controlled period: Dose 1 to 1 month after Dose 2 ,and Dose 1 to the
unblinding date, for Phase 3 participants 12 -15 years of age randomized 1:1 to
BNT162b2 vsplacebo
Safety subgroup analy ses by sex, race, ethnicit y, and baseline SARS -CoV -2 status
from Dose 1 to the unblinding date
b.Open -label observational period : unblinding date to the sBLA data cutoff date
Phase 3 participants 12 -15 years of age originall y randomized to BNT162b2
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COVID -19 Vaccine (BNT162, PF -07302048)
BB-IND 19736
M 1.12.4 Requests for Comments and Advice
PFIZER CONFIDENTIAL
Page 3Phase 3 participants 12- 15 years of age originall y randomized to placebo (Dose 1 and
Dose 2) who then received open -label BNT162b2 (Dose 3 and Dose 4)
Safety subgroup analy sis of participants originall y randomized to placebo who had
confirmed COVID- 19 prior to unblind ing to receive open -label BNT162b2
c.Cumulative follow -up from Dose 1 to 6 months after Dose 2 : Phase 3 participants
12-15years of age originally randomized to BNT162b2 (inclusive of blinded data and
open -label data)
Note that AE anal yses which begin or end attheunblinding date would be summarized as
incidence rates (I R) adjusted for exposure time to account for variable timing of unblinding
for individual participants (per protocol) t o receive BNT162b2 under EUA .
The anal ysis of safet y by time period and anal ysis group is illustrated in Figure 1.
Figure 1.Study C4591001 Phase 3 Safety Analys isTime Periods and Analysis Groups
Dashed horizontal blue/gray line indicates randomized blinded BNT162b2 vs placebo vaccination period.
Dose 3refers to first of two dosesof open -label BNT162b2 administered to participants originally randomized to
placebo (Dose 1 and Dose 2) who then received open -label BN T162b2 (Dose 3 and Dose 4)
1AE data analyzed from Dose 1 to the unblinding date or from unblinding date to the sBLA data cutoff date
will be reported as incidence rates per person -years adjusted for exposure time (which varies per participant ).
2Blind ed placebo -controlled follow -up period until unblinding has duration of<6 months after Dose 2.
3Cumulative follow -up is to ≥6 months after Dose 2 for participants originally randomized to the BNT162b2
group , inclusive of blinded and open -label data.
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BB-IND 19736
M 1.12.4 Requests for Comments and Advice
PFIZER CONFIDENTIAL
Page 42.2.Question 2
Does CBER agree with the proposed criteria for safety narrative s in the planned sBLA
for Study C4591001 participants 12- 15 years of age?
Hybrid(programmed and prose) narratives would be prepared for participants 12 -15years of
age using the same criteria as agreed by CBER for the EUA and BLA :
Deaths, vaccine -related SAEs, safet y-related withdrawals
AEs of interest requested by FDA *(ie, anaph ylaxis, Bell’s palsy, appendicitis, and
pregnancy exposures and outcomes , myocarditis/pericardit is)
AEs corresponding to the CDC list of AEs of special interest ( AESIs ) for COVID-19 ,
ifthere is a numerical imbalance with a higher frequency (or incidence rate) in the
BNT162 b2 group vs placebo group for events that led to withdrawal, considered to be
vaccine -related, or otherwise considered biologically plausible.
COVID -19 cases for participants with severe and/or multiple episodes.
* In lieu of individual narratives on l ymphadenopathy , which ty picall y arerelated AE swith
little additional informati on, wepropos eto provide programmed tables summarizing
incidence , timing relative to Dose 1 or 2, duration , severit y,and re solution of event s.
2.3.Question 3
Does CBER agree that the planned sBLA can be comprised of safety and efficacy data
through at least 6- month follow -up for Study C4591001 participants 12 -15 years of age?
Immunogenicit y and efficacy data in the 12- 15 yearsof age group were previously submitted
for EUA . These data demonstrated that BNT162b2- elicited immune responses in the
12-15years of age group were noninferior to immune responses in the 16-25 years of age
group,meeting immunobridging success criteri a, and participants 12-15 years of agehad an
observed vaccine efficacy of 100% .
In addition to proposed safet yanaly ses (see Question 1), we propose the sBLA to include
updated efficacy anal yses of confirmed COVID- 19cases accrued in placebo -controlled
blinded follow -up through the sBLA data cutoff date , similar to the updated efficacy anal yses
performed for the BLA, but limited to the 12 -15 years of age group. Given that successful
immunobridging has already been demonstrated for this group, no new immunogenicit y
analyses are planned to be performed for the sBLA .
In order to expedientl y submit an sBLA to obtain licensure for individuals ≥ 12 years of age ,
ideally by early 4thquarter 2021, we propose to submit only updated safety and efficacy data
in the sBLA . If CBER requires submission of updated immunogenicity data, this will delay
the sBLA submission due to the additional time needed toanalyze the data. We estimate this
could result in submission of the sBLA at the end of 4thquarter 2021 or early 2022 .
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BB-IND 19736
M 1.12.4 Requests for Comments and Advice
PFIZER CONFIDENTIAL
Page 52.4.Question 4
Does CBER agree with the proposal to submit an sBLA with clinical documents limited
toan interim Clinical Study Report and a Module 2.5 Clinical Overview to report
6-month follow -up data from Study C4591001 participants 12 -15 years of age?
Theproposed sBLA data are derived from a single study /group and can be fully described in
an interim Clinical Study Report andin a M odule 2.5 Clinical Overview (in which additional
benefit:risk context can be provided).
Module 2.7.3 (Summary of Clinical Efficacy )and Module 2.7.4 (Summary of Clinical
Safety ) would not include any additional or unique content .
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Document Approval Record
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