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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 CBER 17 August 2021 Follow -up Information Request Regarding
Safety -Related Postmarketing Requirement/Postmarketing Commitment S tudies
18August 2021
090177e197d79d0b\Approved\Approved On: 18-Aug-2021 15:42 (GMT)
FDA-CBER-2021-5683-0950362
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 AND SPONSOR RESPONSES ................................ ............................ 3
2.1. CBER Request 1 -Study C4591031 ................................ ................................ ......... 3
2.2. CBER Request 2 –Study C459 1007 Evaluation of Troponin I ................................ 4
2.3. CBER Request 3 –Study C4591007 Evaluation of Lower Doses in
Adolescents ................................ ................................ ................................ .................. 5
090177e197d79d0b\Approved\Approved On: 18-Aug-2021 15:42 (GMT)
FDA-CBER-2021-5683-0950363
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 COVID- 19 mRNA Vaccine (COMI RNATY),
for active immunization to prevent COVID -19 caused by SARS -CoV -2 inindividuals
≥16years of age and to CBER’s Information Request received via email on 17August 2021 .
CBER requests are presented in bold italics followed b y Pfizer -BioNTech response in plain
text.
2.CBER REQUESTS AND SPONSOR RESPONSES
Our review of your pharmacovigilance plan for COMIRNATY (COVID- 19 V accine,
mRNA) under BLA STN 125742/0 is ongoing. We have the following comments regarding
the information included in the amendment 51 dated August 16, 2021.
2.1.CBER Request 1 - Study C4591031
For Study C4591031 you have proposed to add a new substudy of 1,000 participants with
documented receipt of 2 prior 30 μg doses of BNT162b2 (the second dose received at least
6 months ago), 16 to 30 years of age (randomized 1:1 in a crossover design to rec eive 30 μg
BNT162b2 or placebo at baseline and the alternative 4 weeks later). For the 1,000
participants in the substudy, you have proposed to schedule a blood draw to obtain a serum
sample for storage and potential future troponin testing, at baseline an d 2-5 days after the
third dose of BNT162b2. You have also indicated that you will prepare to start enrollment
of 1,000 participants into the C4591031 substudy in January 2022. In the context the
proposed substudy, please discuss the feasibility of enrolli ng participants who have not yet
received the first or second dose of BNT162b2 (with enrollment starting as soon as
possible) and also evaluating troponin I levels within 2 to 5 days following the second dose.
Sponsor Response
Since C4591031 is a master pr otocol to evaluate additional dose(s) of BNT 162b2 in healthy
individuals previously vaccinated with BNT 162b2 , it would not be feasible to enroll
participants who have not y et received the first or second dose of BNT162b2 into the
proposed substudy . Further more, recruitment of COVID- 19 vaccine -naïve individuals into a
clinical study in the United States, particularl y with a control group, is not considered to be
feasible at this time. However, since the reactogenicity observed after a 3rddose of
BNT162b2 appears similar to that observed after the 2nddose, if subclinical my ocarditis
exists, and is related to one or more aspects of the immunological response , it could be
anticipated that troponin I findings after a 3rddose could inform what would be observed
after a 2nddose.
We will evaluate opportunities to start enrollment of the 1,000 participants into the
C4591031 substudy earlier than January 2022.
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FDA-CBER-2021-5683-0950364
BNT162b2
BLA STN 125742 /0
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 42.2.CBER Request 2 – Study C4591007 Evaluation of Troponin I
For Study C4591007 you have proposed to add 750 participants 5 to <12 years of age
(randomized 2:1 to receive BNT162b2 10 μg or placebo) and 500 participants 12 -15 years
of age (open label receipt of BNT162b2 30 μg). These participants would be introduced
through a protocol amendment. For these addition al participants you have proposed to
schedule a blood draw to obtain a serum sample for storage and potential future troponin
testing, at baseline and 2 -5 days after the second dose of BNT162b2. We acknowledge the
challenge in projecting a definitive sample size and dates for a study to assess the
incidence of subclinical myocarditis using troponin elevations as a biomarker. However,
should your BLA for this product be approved, we will include the proposed evaluation of
troponin I levels in Study C4591007 as a postmarketing requirement under Section 505(o)
of the Federal Food, Drug and Cosmetic Act. You have previously provided the following
study milestone dates for Study C4591007, which you have proposed as a deferred study
under the Pediatric Research Equity Act (PREA):
Final Protocol Submission: February 8, 2021
Study Completion: October 31, 2023
Final Report Submission: March 31, 2024
For the troponin I evaluation in Study C4591007, please provide the projected Study
Completion and Final Report Submissi on dates if different from those above.
Sponsor Response
The updated dates are provided below.
Study Completion: November 30, 2023
Final Report Submission: May 31, 2024
090177e197d79d0b\Approved\Approved On: 18-Aug-2021 15:42 (GMT)
FDA-CBER-2021-5683-0950365
BNT162b2
BLA STN 125742 /0
M 1.11.3 Response to FDA Information Request
PFIZER CONFIDENTIAL
Page 52.3.CBER Request 3 – Study C4591007 Evaluation of Lower Doses in Adolescents
In response to our request to propose a study(ies) in adolescents 12 through 17 years of
age to evaluate the safety and immunogenicity of lower doses of BNT162b2, we
acknowledge your response that you have submitted protocol amendment 2 to IND 19736
for Study C4591007. This protocol amendment includes Phase 1 evaluation of dose levels
of 3 μg and 10 μg in individuals 12 to <16 years of age and 16 to <30 years of age (32
participants per dose level and age group). Based on the results from Phase 1, one dose
level will be selected for each age group for Phase 3 evaluation of safety and
immunogenicity in 300 participants per age group. You have previously provided the
following study milestone dates for Study C4591007, which you have proposed as a
deferred study under PRE A:
Final Protocol Submission: February 8, 2021
Study Completion: October 31, 2023
Final Report Submission: March 31, 2024
For the proposed dose level evaluation in individuals 12 to <16 years of age and 16 to <30
years of age in Study C4591007, please prov ide the projected Study Completion and Final
Report Submission dates if different from those above.
Sponsor Response
The updated dates are provided below.
Study Completion: November 30, 2023
Final Report Submission: May 31, 2024
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FDA-CBER-2021-5683-0950366
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