02 Pneumococcal Gierke 508

Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation
use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.
Current Epidemiology of Pneumococcal Disease
among Adults, United States
February 2024, ACIP Meeting
February 29, 2024
Ryan Gierke, MPH
Outline
Background on pneumococcal disease
Pneumococcal vaccine coverage in adults
Pneumonia incidence estimates in adults
Invasive pneumococcal disease (IPD)
–Impact of COVID- 19
–Incidence by vaccine type
–Serotype distribution
2
Bogaert, Lancet Infect Dis 2004;4:144 -54Pneumococcal carriage is precursor to pneumococcal disease
More frequent
Less frequent
3
Bogaert, Lancet Infect Dis 2004;4:144 -54Noninvasive Disease
Invasive DiseasePneumococcal carriage is precursor to pneumococcal disease
More frequent
Less frequent
4
PCV20 coverage: 12%
–Ranged from 9% (adults aged ≥85 years) to 25%  (adults aged 65 years)
 PCV15 coverage: 0.2%
–Less than 1% across all agesPCV15 and PCV20 coverage among Medicare Part A/B
beneficiaries aged ≥65 years1, Oct 1, 2021 − Dec  31, 2023
1.Based on age at the end of 2022
Unpublished data courtesy of CDC ISD. Based on CMS data from January 17, 2024.
Estimated proportion of adults who ever received any pneumococcal
vaccination, National Health Interview Survey, 2021
Age group % (95% CI)
Overall (≥65 years) 65.8 (64.4 -67.2)
Overall (19 –64years with risk -based indication ) 22.2 (21.0 -23.5)
White 23.3 (21.7 -24.9)
Black 22.6 (19.2 -26.4)
Hispanic 19.0 (15.9 -22.6)*
Asian 16.9 (12.0 -23.2)*
Other 22.7 (16.3 -30.7)
*p<0.05 for comparisons with white as the referencehttps://www.cdc.gov/vaccines/imz -managers/coverage/adultvaxview/pubs -
resources/vaccination -coverage- adults -2021.html#summary
Estimated incidence of pneumococcal disease in adults
aged ≥65 years
Disease Estimated incidence
(per 100,000 population)
All-cause hospitalized pneumonia1847–3,365
Hospitalized noninvasive pneumococcal
pneumonia2105
Invasive pneumococcal disease (IPD)3 24
1. McLaughlin et al. Vaccine 2020 (limited to studies that collected data during or after 2010)
2. Gierke et al. IDweek 2020. CDC’s Surveillance for NonInvasive  Pneumococcal Pneumonia ( SNiPP ), 2017
3. CDC ABCs, 2018 –2019 Case fatality ratio from IPD: 14%3
Kobayashi October 2022 ACIP meeting presentation 7
IPD Incidence and Serotype Distribution Among
Adults in the United States
8
Methods
Active Bacterial Core surveillance (ABCs):
Active laboratory and population- ba sed
surveillance, 10 sites
Pneumococcus  is olation from sterile site
Isolates serotyped by whole -ge nome sequencing, Quellung, or PCR at reference
labs and grouped for analysis by vaccine type
US Census Bureau race -b ridged post -census population estimates used as
denominators
Overall and serotype -s pecific IPD incidence rates (cases per 100,000 population)
https://www.cdc.gov/abcs/methodology/surv-pop.html9
IPD incidence rates, by age group, 2007 − 2022
051015202530354045
2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022Cases per 100,000 population
YearAge <5 Age 19-49
Age 50-64 Age ≥65
10
051015202530354045
2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022Cases per 100,000 population
YearAge <5 Age 19-49
Age 50-64 Age ≥65IPD incidence rates, by age group, 2007 − 2022
PCV13: children
11
051015202530354045
2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022Cases per 100,000 population
YearAge <5 Age 19-49
Age 50-64 Age ≥65IPD incidence rates, by age group, 2007 − 2022
PCV13: adultsPCV13: children
12
051015202530354045
2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022Cases per 100,000 population
YearAge <5 Age 19-49
Age 50-64 Age ≥65IPD incidence rates, by age group, 2007 − 2022
PCV13: adultsPCV13: children
13COVID -19
051015202530354045
2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022Cases per 100,000 population
YearAge <5 Age 19-49
Age 50-64 Age ≥65IPD incidence rates, by age group, 2007 − 2022
PCV15 & PCV20:
adultsPCV13: adultsPCV13: children
PCV15:  children
14COVID -19
Proportion of adult IPD cases, with a risk -based indication,
2018 − 2021
Among adult IPD cases, 82% – 87% had at least one risk -based
indication for pneumococcal vaccination
–Age 19- 49 years: 82%
–Age 50 -64 years: 87%
–Age ≥65 years: 87%
15
Serotypes contained in current and new pneumococcal vaccines
1 3 4 5 6
A6B7 F9V1418C19A19F23F22F33F8 1
0
A1
1
A1
2
F1
5
B2 9
N17
F2015
A1
5C16F23A23B24F3135B
PCV15
PCV20PPSV23PCV21
16
Serotypes contained in PCV20 and PCV21
1 3 4 5 6
A6B7 F9V1418C19A19F23F22F33F8 1
0
A1
1
A1
2
F1
5
B2 9
N17
F2015
A1
5C16F23A23B24F3135B
PCV20
PCV21
17
1 3 4 5 6
A6B7 F9V1418C19A19F23F22F33F8 1
0
A1
1
A1
2
F1
5
B2 9
N17
F2015
A1
5C16F23A23B24F3135B
PCV20
PCV21
For analysis purposes:
•PCV20 non- PCV21: includes serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F, 15B
18Serotypes contained in PCV20 and PCV21
1 3 4 5 6
A6B7 F9V1418C19A19F23F22F33F8 1
0A1
1
A1
2
F1
5
B2 9
N17
F2
015
A1
5C16F23A23B24F3135B
PCV20
PCV21
For analysis purposes:
•PCV20 non- PCV21: includes serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F, 15B
•PCV20 and PCV21: includes serotypes 3, 6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F, +6C
19Serotypes contained in PCV20 and PCV21
1 3 4 5 6
A6B7 F9V1418C19A19F23F22F33F8 1
0
A1
1
A1
2
F1
5
B2 9
N17
F2015
A1
5C16F23A23B24F3135B
PCV20
PCV21
For analysis purposes:
•PCV20 non- PCV21: includes serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F, 15B
•PCV20 and PCV21: includes serotypes 3, 6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F, +6C
•PCV21 non- PCV20:  includes serotypes 9N, 17F, 20, 15A, 15C, 16F, 23A, 23B, 24F, 31, 35B
20Serotypes contained in PCV20 and PCV21
IPD incidence rates among adults 19 -64 years old, by vaccine type,
2011 – 2022
PCV15 & PCV20: adults19-49 years old 50-64 years old
02468101214161820
2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022*Cases per 100,000 population
YearsPCV20/ non-PCV21 PCV20 and PCV21
PCV21/non-PCV20 Non-Vaccine Type
PCV20/ non- PCV21 serotype:  1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F, 15B
PCV20/ in -PCV21 serotypes: 3, 6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F, +6C
PCV21/ non -PCV20  serotypes: 9N, 17F ,20, 15A, 15C, 16F, 23A, 23B, 24F, 31, 35B 02468101214161820
2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022*Cases per 100,000 population
YearsPCV20/ non-PCV21 PCV20 and PCV21
PCV21/non-PCV20 Non-Vaccine Type
*2022 estimates are not finalized
21COVID -19COVID -19
02468101214161820
2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022*Cases per 100,000 population
YearsPCV20/ non-PCV21 PCV20 and PCV21
PCV21/non-PCV20 Non-Vaccine Type
02468101214161820
2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022*Cases per 100,000 population
YearsPCV20/ non-PCV21 PCV20 and PCV21
PCV21/non-PCV20 Non-Vaccine TypeIPD incidence rates among adults 19 -64 years old, by vaccine type,
2011 – 2022
19-49 years old 50-64 years old
PCV20/ non- PCV21 serotype:  1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F, 15B
PCV20/ in -PCV21 serotypes: 3, 6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F, +6C
PCV21/ non -PCV20  serotypes: 9N, 17F ,20, 15A, 15C, 16F, 23A, 23B, 24F, 31, 35B *2022 estimates are not finalized
22COVID -19
COVID -19
0510152025303540
2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022Cases per 100,000 population
YearsPCV20/ non-PCV21 PCV20 and PCV21 PCV21/ non-PCV20 Non-Vaccine TypeIPD incidence rates among adults ≥65 years old, by vaccine type,
2011 – 2022
PCV15 & PCV20:
adultsPCV13: adults ≥65
PCV20/ non- PCV21 serotype:  1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F, 15B
PCV20/ in -PCV21 serotypes: 3, 6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F, +6C
PCV21/ non -PCV20  serotypes: 9N, 17F ,20, 15A, 15C, 16F, 23A, 23B, 24F, 31, 35B *
*2022 estimates are not finalized
23COVID -19
1345366
0102030405060708090100Percent IPD
PCV20/ non-PCV21 PCV20 and PCV21
PCV21/ non-PCV20 NVT747388
0102030405060708090100Percent IPD
PCV20/ non-PCV21 PCV20 and PCV21
PCV21/ non-PCV20 NVTProportion of IPD by vaccine -type among adults with a pneumococcal
vaccine indication, 2018 − 2022
PCV20/ non- PCV21 serotype:  1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F, 15B
PCV20/ in -PCV21 serotypes: 3, 6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F, +6C
PCV21/ non -PCV20  serotypes: 9N, 17F ,20, 15A, 15C, 16F, 23A, 23B, 24F, 31, 35B PCV21:
85%  coverage
24PCV20:
54%  coveragePCV21:81%  coverage
PCV20:
58%  coverage19-64 years old (with a risk -based indication) ≥65 years old
Conclusion
During the COVID- 19 pandemic, rates of IPD declined but are now returning
to pre -pandemic levels
>80% of adult IPD cases have a risk -based indication for vaccination
PCV21 has greater coverage of the serotypes causing IPD in adults compared
to PCV20
–PCV20 covers 54–58% of adult IPD
–PCV21 covers 81–84% of adult IPD
25
For more information, contact CDC
1-800- CDC- INFO (232 -4636)
TTY:  1 -888 -232-6348    www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official
position of the Centers for Disease Control and Prevention.
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation
use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.
Questions
Supplemental slides
27
Serotypes contained in current and new pneumococcal vaccines
1 3 4 5 6
A6B7 F9V1418C19A19F23F22F33F8 1
0
A1
1
A1
2
F1
5
B2 9
N17
F2015
A1
5C16F23A23B24F3135B
PCV15
PCV20PPSV23PCV21
For analysis purposes:
•PCV15+6C  includes serotype 6C with PCV15 types due to cross protection from 6A
antigen
28
Serotypes contained in current and new pneumococcal vaccines
1 3 4 5 6
A6B7 F9V1418C19A19F23F22F33F8 1
0
A1
1
A1
2
F1
5
B2 9
N17
F2015
A1
5C16F23A23B24F3135B
PCV15
PCV20PPSV23PCV21
29For analysis purposes:
•PCV15+6C  includes serotype 6C with PCV15 types due to cross protection from 6A
antigen
•PCV20/ non- PCV15: includes serotypes  8, 10A, 11A, 12F, and 15B
1 3 4 5 6
A6B7 F9V1418C19A19F23F22F33F8 1
0
A1
1
A1
2
F1
5
B2 9
N17
F2015
A1
5C16F23A23B24F3135B
PCV15
PCV20PPSV23PCV21
For analysis purposes:
•PCV15+6C includes serotype 6C with PCV15 types due to cross protection from 6A
antigen
•PCV20/ non- PCV15: includes serotypes 8, 10A, 11A, 12F, and 15B
•PPSV23/ non- PCV20:  includes serotypes  2, 9N, 17F, and 20
30Serotypes contained in current and new pneumococcal vaccines
1 3 4 5 6
A6B7 F9V1418C19A19F23F22F33F8 1
0
A1
1
A1
2
F1
5
B2 9
N17
F2015
A1
5C16F23A23B24F3135B
PCV15
PCV20PPSV23PCV21
For analysis purposes:
•PCV15+6C includes serotype 6C with PCV15 types due to cross protection from 6A
antigen
•PCV20 non- PCV15: includes serotypes 8, 10A, 11A, 12F, and 15B
•PPSV23 non- PCV20:  includes serotypes  2, 9N, 17F, and 20
•PCV21 non- PPSV23:  includes serotypes 15A, 15C, 16F, 23A, 23B, 24F, 31, 35B
31Serotypes contained in current and new pneumococcal vaccines
02468101214161820
2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022Cases per 100,000 persons
YearPCV15+6C PCV20/ non-PCV15 PPSV23/ non-PCV20
PCV21/non-PPSV23 Non-Vaccine TypeIPD incidence rates among adults 19 -64 years old, by vaccine type,
2011 – 2022
PCV20 non- PCV15 serotypes: 8, 10A, 11A, 12F, 15B
PPSV23 non -PCV20 serotypes: 2, 9N, 17F, 20
PCV21 non- PPSV23 serotypes: 15A, 15C, 16F, 23A, 23B, 24F, 31, 35 19-49 years old 50-64 years old
02468101214161820
2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022*Cases per 100,000 persons
YearPCV15+6C PCV20/ non-PCV15 PPSV23/ non-PCV20
PCV21/non-PPSV23 Non-Vaccine Type
*2022 estimates are not finalized*
32
0510152025303540
2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022*Cases per 100,000 persons
YearPCV15+6C PCV20/ non-PCV15 PPSV23/ non-PCV20 PCV21/non-PPSV23 Non-Vaccine TypeIPD incidence rates among adults ≥65 years old, by vaccine type,
2011 – 2022
PCV15 & PCV20:
adults
PCV20 non- PCV15 serotypes: 8, 10A, 11A, 12F, 15B
PPSV23 non -PCV20 serotypes: 2, 9N, 17F, 20
PCV21 non- PPSV23 serotypes: 15A, 15C, 16F, 23A, 23B, 24F, 31, 35 PCV13: adults ≥65
*2022 estimates are not finalized
33
1345366
0102030405060708090100Percent IPD
PCV20/ non-PCV21 PCV20 and PCV21
PCV21/ non-PCV20 NVT421615216
0102030405060708090100Percent IPD
PCV15+6C PCV20/non-PCV15
PPSV23/non-PCV20 PCV21/non-PPSV23
NVTProportion of IPD by vaccine -type among adults aged 19 -64 years, with a
risk-based indication, 2018 -2022
PCV20/ non- PCV15 serotypes: 8, 10A, 11A, 12F, 15B
PPSV23/ non -PCV20 serotypes: 9N, 17F ,20
PCV21/ non- PPSV23 serotypes: 15A, 15C, 16F, 23A, 23B, 24F, 31, 35 81%
coverage
58% coverage
PCV20/ non- PCV21 serotype:  1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F, 15B
PCV20/ in -PCV21 serotypes: 3, 6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F, +6C
PCV21/ non -PCV20  serotypes: 9N, 17F ,20, 15A, 15C, 16F, 23A, 23B, 24F, 31, 35 34
747388
0102030405060708090100Percent IPD
PCV20/ non-PCV21 PCV20 and PCV21 PCV21/ non-PCV20 NVT42129298
0102030405060708090100Percent IPD
PCV15+6C PCV20/ non-PCV15 PPSV23/ non-PCV20
PCV21/ non-PPSV23 NVTProportion of IPD by vaccine -type among adults age ≥65 years,
2018 -2022
PCV20/ non- PCV15 serotypes: 8, 10A, 11A, 12F, 15B
PPSV23/ non -PCV20 serotypes: 2, 9N, 17F ,20
PCV21/ non- PPSV23 serotypes: 15A, 15C, 16F, 23A, 23B, 24F, 31, 35 PCV20/ non- PCV21 serotype:  1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F, 15B
PCV20/ in -PCV21 serotypes: 3, 6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F, +6C
PCV21/ non -PCV20  serotypes: 9N, 17F ,20, 15A, 15C, 16F, 23A, 23B, 24F, 31, 35 PCV21:
85%  coverage
PCV20:54%  coverage
35

Summary: Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Current Epidemiology of Pneumococcal Disease  among Adults, United States February 2024, ACIP Meeting February 29, 2024 Ryan Gierke, MPH Outline Background on…


03 Pneumococcal Self 508

Public
Interim Results from the PNEUMO Study
.
Pneumococcal pNeumonia Epidemiology, Urine serotyping, and
Mental Outcomes study
February 29, 2024
Study Leadership
Wesley H. Self, MD
Vanderbilt UniversityJ. Jackson Resser , MS
Vanderbilt UniversityKelly D. Johnson, PhDMerck & Co., Inc.
1 Funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USANadine Rouphael , MD
Emory University
Public
PNEUMO study overview
•Adults 18+ years hospitalized with
community acquired pneumonia (CAP)Target
Population
•Multi -country, prospective, population -
based active surveillance studyDesign
•Estimate pneumococcal pneumonia
incidence and serotype prevalence (using
Merck PCV15 and V116 SSUADs), with
longitudinal evaluation of functional status, quality of life and costObjectives►Incidence hospitalized pneumococcal CAP
►Incidence hospitalized PCV15-  and
V116 - type pneumococcal CAP
►Direct medical cost
►Work loss
►Functional status
►Cognitive status
►Quality of Life (EQ -5D)Up to 6
months
post -
discharge
2
Public
Pneumonia surveillance  with prospective, real -time enrollment of
adults hospitalized with CAP (including HCAP)
HCAP, healthcare associated pneumonia US PNEUMO sites: enrollment Sept 2018 - present
Nashville, Tennessee
(2 hospitals) Atlanta, Georgia
3
PublicEligibility criteria
Inclusion  Criteria
1.Age ≥ 18 years  old
2.Hospitalized
3.Clinical signs and/or  symptoms of an acute  respiratory  illness (e.g., new  shortness of breath,  cough)
4.Clinical signs and/or  symptoms of an acute  infection (e.g., fever,  leukocytosis)
5.Radiologic  evidence  of pneumonia  interpreted  by a radiologist  (x-ray or CT)
Exclusion  Criteria
1.Prior enrollment  in this study  within  the past  30 days  (to avoid  multiple  enrollments for same  episode  of
pneumonia).
2.Development  of pneumonia  >72 hours  after  hospital admission
3.Inability  to obtain  consent  within  72 hours  of hospital admission
4.Inability  or unwillingness of the patient  to provide  a urine  sample  within  72 hours  of hospital admission .
5.Non -pneumonia  illness completely  explains the patient’s  acute  symptoms.  4
Public
Tests for S. pneumoniae
•Urine collection from patients at enrollment
    (1) BinaxNow pneumococcal urinary antigen test (local testing by research team)

 (2) Serotype- specific urinary antigen detection (SSUAD) assays:
•Developed and performed by Merck laboratory
•30 serotypes:
•1, 3, 4, 5, 6A*, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15A, 15C#, 16F, 17F, 18C, 19A, 19F, 20A, 22F,
23A, 23B, 23F, 24F, 31, 33F, 35B
•All serotypes in PCV15, PCV20, and V116 included except 15B
•Results of clinically -obtained bacterial cultures:
•Sterile sites: blood, pleural fluid, BAL fluid, CSF, synovial fluid
•Non -sterile sites: high-quality respiratory samples (>25 WBC, <10 epi)
•sputum, endotracheal aspirate
5* assay for serotype 6A has cross- reactivity with serotype 6C
# assay for serotype 15C has mild cross- reactivity with serotype 15B
Public
Hospitalized adults screened for
eligibility
(n = 5,385)
Enrolled: adults hospitalized with
community acquired pneumonia (CAP)
(n = 3,278)
Analyzed
[All-cause CAP population]
(n = 2,917)
S. pneumoniae detected
[Pneumococcal CAP population]
(n = 352)S. pneumoniae not  detected
[Non -pneumococcal CAP]
(n = 2,565)
S. pneumoniae culture positive
from normally sterile site
[Invasive pneumococcal CAP]
(n = 51)S. pneumoniae detected outside
normally sterile site only
[Non -invasive pneumococcal CAP]
(n = 301)Not enrolled (n =2,107)
Enrolled, not analyzed (n = 361)
•No radiographic evidence of pneumonia (n=235)
•Urine not tested by SSUAD (n = 114)
•Patient withdrew (n = 12)Enrolled Patients
12.1%
pneumococcal
prevalence
85.5%
of pneumococcal pneumonia
was non- invasive
PublicPatient Characteristics: Demographics
Characteristic Pneumonia with
S. pneumoniae detected
(n= 352)Pneumonia without
S. pneumoniae detected
(n= 2565)P-value
Age in years, median (IQR) 60.3 (50.6, 70.2) 60.5 (46.8, 70.2) 0.34
Age category, n (%) 0.01
18-49 years 85 (24.1%) 767/2564 (29.9%)
50-64 years 141 (40.1%) 817/2564 (31.9%)
≥65 years 126 (35.8%) 980/2564 (38.2%)
Female sex assigned at birth, n (%) 167/350 (47.7%) 1147/2558 (44.8%)
Race, n (%) <0.01
White 198 (56.2%) 1771 (69.0%)
Black 145 (41.2%) 703 (27.4%)
Asian 1 (0.3%) 38 (1.5%)
American Indian/Native
Alaskan2 (0.6%) 14 (0.5%)
Native Hawaiian/Pacific Islander2 (0.6%) 6 (0.2%)
Other 6 (1.7%) 54 (2.1%)
Ethnicity, n (%) 0.95
Not Hispanic 328 (93.2%) 2394 (93.3%)
Hispanic 14 (4.0%) 94 (3.7%)
Unknown 10 (2.8%) 77 (3.0%)7
Public
Characteristic Pneumonia with
S. pneumoniae detected
(n= 352)Pneumonia without
S. pneumoniae detected
(n= 2565)P-value
Type of home before illness, n (%) 0.27
Community dwelling 320 (90.9%) 2382 (92.9%)
Nursing Home 6 (1.7%) 43 (1.7%)
Assisted Living 6 (1.7%) 33 (1.3%)
Rehabilitation hospital 1 (0.3%) 13 (0.5%)
School housing 0 (0.0%) 0 (0.0%)
Homeless/shelter 12 (3.4%) 40 (1.6%)
Other 3 (0.9%) 33 (1.3%)
Unknown 4 (1.1%) 21 (0.8%)
Ever regularly smoked tobacco, n (%) 205/349 (58.7%) 1232/2554 (48.2%) <0.01
Alcohol use >3 days/week, n (%) 30/348 (8.6%) 145/2543 (5.7%) 0.03
Use of opioids at least weekly, n (%) 68/339 (20.1%) 438/2462 (17.8%) 0.31
Interacts with child <5 years old at
least once per week, n (%)122/340 (35.9%) 682/2468 (27.6%) <0.01
Lives with children, n (%) 83/346 (24.0%) 517/2534 (20.4%)Patient Characteristics: Social History
8
Public
Characteristic Pneumonia with
S. pneumoniae detected
(n= 352)Pneumonia without
S. pneumoniae detected
(n= 2565)P-value
Chronic medical conditions, n (%)
Dementia 11/349 (3.2%) 65/2528 (2.6%) 0.362
COPD 97/346 (28.0%) 487/2510 (19.4%) <0.001
Asthma 72/346 (20.8%) 474/2518 (18.8%) 0.413
Heart failure 61/340 (17.9%) 446/2509 (17.8%) 0.824
Prior MI 37/344 (10.8%) 231/2525 (9.1%) 0.359
Prior stroke 38/347 (11.0%) 255/2516 (10.1%) 0.651
End stage kidney disease with
chronic kidney replacement14/342 (4.1%) 125/2515 (5.0%) 0.424
Diabetes mellitus 82/348 (23.6%) 684/2525 (27.1%) 0.159
Chronic liver disease 30/343 (8.7%) 173/2508 (6.9%) 0.254
Immunosuppression 72/343 (21.0%) 529/2499 (21.2%) 0.983
Solid organ cancer 80/348 (23.0%) 589/2501 (23.6%) 0.981
Hematologic cancer 30/346 (8.7%) 193/2511 (7.7%) 0.598
Solid organ transplant 25/347 (7.2%) 205/2528 (8.1%) 0.545
Pregnant 0/348 (0.0%) 22/2533 (0.9%) 0.081
Obesity with body mass index
>30 kg/m289/355 (25.9%) 1009/2479 (40.7%) <0.001Patient Characteristics: Chronic Medical Conditions
9
Public
Characteristic Pneumonia with
S. pneumoniae detected
(n= 352)Pneumonia without
S. pneumoniae detected
(n= 2565)P-value
Received antibiotics for current illness before
hospitalization, n (%)71/328 (21.6%) 613/2297 (26.7%) 0.05
Duration of acute illness prior to hospital admission [days], median (IQR)2.6 (1.3, 5.0) 2.7 (1.1, 5.7) 0.36
CURB- 65* score at hospital admission, n (%) 0.17
0 (low risk) 123/345 (35.7%) 943/2523 (37.4%)
1 (low risk) 126/345 (36.5%) 869/2523 (34.4%)
2 (moderate risk) 60/345 (17.4%) 547/2523 (21.7%)
3 (high risk) 31/345 (9.0%) 150/2523 (5.9%)
4 (high risk) 5/345 (1.4%) 14/2523 (0.6%)
5 (high risk) 0/345 (0.0%) 0/2523 (0.0%)
Timing of Enrollment <0.01
Before COVID- 19 in US (October 2018 –
February 2020)231/345 (67.0%) 1249/2519 (49.6%)
After COVID- 19 in US (March 2020 –
October 2022)114/345 (33.0%) 1270/2519 (50.4%)Patient Characteristics: Acute Illness
10* CURB -65: pneumonia severity scoring system, consisting of the following variables: confusion, uremia, respiratory rate, blood pressure, age >65
Public
BinaxNOW
125 patients positive
Cultures
56 patients positive44 53 SSUAD
283 patients positive 199
1117523352 Patients with ≥1 Positive Pneumococcal Test
12Percentage of Pneumococcal Serotype Detections
14.6%
9.8%
7.0%
6.0%5.7%5.4%5.1%4.7%4.1%3.5%3.2%2.8%2.2%1.9%1.6%1.3%0.9% 0.3% 0.0%
n=46 n=31 n=22 n=19 n=18 n=17 n=16 n=15 n=13 n=11 n=10 n=9 n=7 n=6 n=5 n=4 n=3n=1n=0
3 22F 19A 35B 9N 19F 23A 11A 23B 7F, 8,
17F, 316A/C 16F,
20A1, 5 9V, 15C 15A 33F 4, 6B,
24F14, 10A,
12F18C,
23F
Serotype316 serotypes detected by SSUAD (denominator) among 283 unique patients
13Vaccine Category Pneumococcal serotypes% of serotypes in adults
hospitalized with CAP
(n=2917)
V116 (21 serotypes) 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F, 35B 9.3%
PCV20  (19 serotypes; serotype 15B not tested) 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 18C, 19A, 19F, 22F, 23F, 33F 6.7%
PCV15  (15 serotypes) 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F 5.8%
V116 and not PCV15 or PCV20 (11 serotypes) 9N, 15A, 15C, 16F, 17F, 20A, 23A, 23B, 24F, 31, 35B 4.1%8.0%11.3%
8.7%
4.7%8.4%
6.9%
4.0%7.3%
5.8%
4.0%4.8%
3.1%
0%2%4%6%8%10%12%
18-49 years old (n=852) 50-64 years old (n=958) 65+ years old (n=1107)% of patients with ≥1 serotype in categoryV116 PCV20 PCV15 11 unique V116 serotypesPercentage of Pneumococcal Serotype by Vaccine in Adults Hospitalized with CAP
Public
Conclusions
•Pneumococcal CAP remains a major cause of adult hospitalizations
•SSUAD assays greatly increase S. pneumoniae detection over traditional testing
•Among adults hospitalized with CAP:
•12.1% with S. pneumoniae detected
•9.3% with a pneumococcal serotype in V116
•4.1% with a serotype unique to V116 (not PCV15 or PCV20)
•Most commonly detected serotypes unique to V116: 35B, 9N, 23A, 23B
14

Summary: Public Interim Results from the PNEUMO Study .  Pneumococcal pNeumonia Epidemiology, Urine serotyping, and  Mental Outcomes study February 29, 2024 Study Leadership Wesley H. Self, MD Vanderbilt UniversityJ. Jackson Resser , MS Vanderbilt UniversityKelly D. Johnson, PhDMerck & Co., Inc. 1 Funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USANadine Rouphael , MD Emory University Public PNEUMO study overview •Adults 18+ years hospitalized with  community acquired…


04 Pneumococcal Platt 508

V116: An Investigational Adult Specific Pneumococcal
Conjugate Vaccine
Key Results from the Phase 3 Clinical Development Program
ACIP Meeting, 29 -Feb -2024
Heather Platt, M.D., on behalf of the V116 team
Distinguished Scientist, Global Clinical Development
Merck Research Laboratories
Merck & Company, Inc.
Presentation Rationale for Development of V116
 Overview of V116 Adult Clinical Development Program
 Immunogenicity Results
•Vaccine naïve adults ≥18 years of age
•Vaccine experienced adults ≥50 years of age
Integrated Summary of Safety
•Vaccine naïve and vaccine experienced adults ≥18 years of age
 Supportive Studies
•V116 in individuals living with HIV
•V116 administered with concomitant influenza vaccine
•V116 lot consistency
 Conclusions
 Questions
2
Confidential
The introduction of PCVs has significantly decreased disease incidence
in children and changed epidemiology of IPD in adults in the US
387.6
1.85.9
5.3
020406080100
Pre-PCV Post-PCV
PCV13 Non PCV13
*Centers for Disease Control and Prevention, IPD serotype data 2019, as compiled from data provided through Active Bacterial Core surveillance (ABCs). IPD cases per 100K in US by serotype, children <5
94
7IPD cases per 100K in US by serotype, adults ≥65
45.9
5.415.1
18.6
020406080100
Pre-PCV Post-PCV
PCV13 Non PCV1361
24
Confidential
Rationale for Development of V116
4
 The burden of disease in adults remains high; IPD due to non -
vaccine serotypes has increased in adults.
V116 being developed as a  population -specific  vaccine to prevent invasive
disease and pneumonia in adults.
V116 is designed to  complement PCV pediatric immunization
programs.  PCV use in infants has significantly decreased the burden of
disease in adults  through indirect protection .
Population -specific
vaccinationUnmet medical need
in adultsIndirect protection
through pediatric vaccination
Complementary to
 pediatric PCVs
V116 is an adult specific  pneumococcal conjugate vaccine (PCV)
IPD, invasive pneumococcal disease; PCV, pneumococcal conjugate vaccine; PCV13, pneumococcal conjugate vaccine, 13 -valent; PCV15  pneumococcal conjugate vaccine, 15 -valent, PCV20, pneumococcal conjugate vaccine, 20 -valent.
1. CDC , IPD Serotype Data 2019, as compiled from data provided through Active Bacterial Core surveillance (ABCs).
2. 2. Platt H , Omole T, Cardona J, Fraser NJ, Mularski  RA, Andrews C, Daboul  N, Gallagher N, Sapre A, Li J, Polis A, Fernsler D, Tamms G, Xu W, Murphy R, Skinner J, Joyce J, Musey  L. Safety, tolerability, and immunogenicity of a 21 -valent pneumococcal
conjugate vaccine, V116, in healthy adults: phase 1/2, randomised , double -blind, active comparator -controlled, multicentre , US -based trial. Lancet Infect Dis. 2023 Feb;23(2):233 -246. https://pubmed.ncbi.nlm.nih.gov/36116461/
15C is denoted here to represent the serotype protection proposed with deOAc15B as the molecular structures for deOAc15B and 15C are similar (Jones C, Lemercinier  X. 2005. Full NMR assignment and revised structure for the capsular polysaccharide from
Streptococcus pneumoniae type 15B. Carbohydr  Res 340:403 –409.) •Includes 21 pneumococcal serotypes , 4µg/PnPs individually conjugated to CRM197 formulated without an adjuvant
•Single dose, 0.5mL pre-filled syringe , intramuscular injection for adults 18+
•The serotypes in V116 accounted for ~85% of IPD and the 8 unique serotypes accounted for  ~30% of IPD in US
adults ≥65 years in 2019
•V116 is currently under Priority Review by the FDA for the prevention of IPD and pneumonia in adults  ≥18 years of
age with target action date of June 17, 2024.
Serotype Composition
PCV13 4 6B 9V 14 18C 19F 23F 1 3 5 6A 7F 19A
PCV15 4 6B 9V 14 18C 19F 23F 1 3 5 6A 7F 19A 22F 33F
PPSV23 4 6B 9V 14 18C 19F 23F 1 3 5 7F 19A 22F 33F 2 8 9N 10A 11A 12F 15B 17F 20
PCV20 4 6B 9V 14 18C 19F 23F 1 3 5 6A 7F 19A 22F 33F 8 10A 11A 12F 15B
V116 3 6A 7F 19A 22F 33F 8 9N 10A 11A 12F 17F 20A 15A 15C 16F 23A 23B 24F 31 35B
5Confidential
Source: US Centers for Disease Control and Prevention, IPD serotype data 2019, as compiled from data provided through Active Bac terial Core surveillance (ABC).In adults 50 –64 and ≥65 years of age, serotypes in V116 are responsible for the
majority of residual IPD in adults
IPD coverage (% of serotypes and cases per 100,000) in US Adults 50 –64 and ≥65 years of age, 2019
38.9%55.5%67.9% 67.7%83.4%
40.2%52.9%60.2% 60.0%84.8%
PCV15 PCV20 PCV24 PPSV23 V116
PCV15 V116 PPSV23 PCV24 PCV20≥65~6 cases ~9 cases ~11 cases ~11 cases ~13 cases ~9 cases ~12 cases ~14 cases ~14 cases ~20 cases
50-64 50-64 50-64 50-64 50-64 ≥ 65 ≥ 65 ≥ 65 ≥ 65
6
V116 Phase 3 Clinical
Development Program
7
Confidential
V116 Clinical Development Program focused on enrolling participants at
risk for pneumococcal disease
8V116 -007
High Risk (HIV)
(n=300)V116 -008
At-Risk Adults
(n=900)V116 -P004
 Clinical Lot  Consistency
(n=2040)V116 -P003
Pivotal
(n=2600)V116 -P005
Concomitant Flu
(n=1000)V116 -P006
Vaccine Experienced
(n=700)
≥ 18 years old 18 – 64 years old18 – 49 years old ≥ 50 years old ≥ 18 years old
V116 -013
Pediatric with Increased Risk
(n=820)
≥ 2 - <18 years old
Confidential
4 Studies in the V116 BLA submission represent a broad,
diverse patient population
9V116 -007
High Risk (HIV)
(n=300)V116 -008
At-Risk Adults
(n=900)V116 -P004
 Clinical Lot  Consistency
(n=2040)V116 -P003
Pivotal
(n=2600)V116 -P005
Concomitant Flu
(n=1000)V116 -P006
Vaccine Experienced
(n=700)
≥ 18 years old 18 – 64 years old18 – 49 years old ≥ 50 years old ≥ 18 years old
V116 -013
Pediatric with Increased Risk
(n=820)
≥ 2 - <18 years old

Confidential
Safety Endpoints Immunogenicity Endpoints
OPA responses supported primary objectives:
•Serotype specific OPA Geometric Mean Titers (GMTs)
•Proportion of participants with ≥4-fold rise in OPA
responses from baseline to Day 30 postvaccination
OPA and IgG responses supported secondary objectives:
•Serotype specific IgG Geometric Mean Concentrations
(GMCs)
•Proportion of participants with ≥4-fold rise in IgG
responses from baseline to Day 30 postvaccination
•Geometric Mean Fold Rise (GMFR) of OPA and IgG
responses
•Reverse Cumulative Distribution Curves (RCDCs) for
OPA and IgG responsesImmunogenicity & Safety Endpoints in the V116 Program
Participants reported adverse events on an electronic vaccine report
card.Primary Safety Endpoints:
•Solicited injection site events Day 1 -5
postvaccination: erythema, swelling, injection -site
pain
•Solicited systemic events Days 1 -5 postvaccination:
headache, myalgia, fatigue
•Serious vaccine -related events Day 1 through the
duration of participation in the study
Additional Safety Endpoints:
•Unsolicited AEs, Vaccine related AEs, Any SAE
•Maximum temperature Day 1 -5 postvaccination
Immune responses were assessed in validated multiplex
opsonophagocytic (OPA) and electrochemiluminescence (ECL IgG)
assays 10
¹Weber Shandwick/KCR Research, 2020 / AMO 2019V116 -003A Phase 3, Randomized, Double -blind, Active
Comparator -controlled Clinical Study to
Evaluate the Safety, Tolerability, and
Immunogenicity of V116 in Pneumococcal
Vaccine -naïve Adults
11
Confidential
V116 -003 Study Design
V116  or  PCV20
Prevaccination
Immunogenicity
(Day 1)
eVRC , solicited AEs
Serious and nonserious AEs  Serious AEs
Postvaccination
Immunogenicity
(Day 30)Cohort 1 ( ≥50 years of age)
N=2362 Participants
randomized 1:1,V116 to PCV20
(Stratified by age: 50 -64, 65 -74, 75 -84, ≥85)
Cohort 2 (18 -49 years of age)
N=301 Participants
randomized 2:1,V116 to PCV20
Immunogenicity
assessment
Safety
assessmentDay 1 Day 5 Day 7 Day 90 Day 30 Month 6Pivotal Study
1 3 2 4 5
12
V116 -003: Primary study objectives
Primary safety Primary immunogenicity
In adults ≥50 years:
•Demonstrate that V116 is noninferior  to PCV20 for
10 common serotypes
–Lower bound of the 2 -sided 95% CI of the OPA GMT ratio
(V116/PCV20) to be >0.5
•Demonstrate that V116 is superior  to PCV20 for
11 unique serotypes
–Lower bound of the 2 -sided 95% CI of the OPA GMT ratio
(V116/PCV20) to be >2.0
–2-sided 95% CI of the differences (V116 – PCV20) between the
proportions of participants with a ≥4-fold rise to be >10%
In adults 18 –49 years:
•Demonstrate V116 immunobridges  to adults 50 -64
years of age for 21 serotypes in V116
–Lower bound of the 2 -sided 95% CI of the OPA GMT ratio
(V116 18 -49/V116 50 –64 years ) to be >0.5•To evaluate the safety and tolerability of V116 as
assessed by the proportion of participants with adverse
events (AEs)
–Solicited injection site events Day 1 –5 postvaccination:
erythema, swelling, injection -site pain
–Solicited systemic events Days 1–5 postvaccination:
headache, myalgia, fatigue
–Serious vaccine -related events Day 1 through the duration of
participation in the studyPivotal Study
13
Confidential
V116 -003 Baseline Characteristics
In each cohort, baseline characteristics were balanced between the treatment groups
Risk Factors includes prespecified medical history conditions: Alcoholism, Chronic Heart Disease, Chronic Kidney Disease, Chr onic Liver Disease, Chronic Lung Disease, Diabetes, Smoking.14Cohort 1 (Age ≥50 years) Cohort 2 (Ages 18 -49 years)
V116, N=1179 PCV20, N=1177 V116, N=200 PCV20, N=100
Sex
Female 687 (58.3) 670 (56.9) 137 (68.5) 64 (64.0)
Age ( yr)
Median (min to max) 65 (50 -91) 65 (50 -97) 36 (18 -49) 34 (18 -49)
18-49, n (%) 0 (0) 0 (0) 200 (100) 100 (100)
50 to 64, n (%) 589 (50.0) 587 (49.9) 0 (0) 0 (0)
65 to 74, n (%) 464 (39.4) 464 (39.4) 0 (0) 0 (0)
75-84, n (%) 112 (9.5) 113 (9.6) 0 (0) 0 (0)
≥85, n (%) 14 (1.2) 13 (1.1) 0 (0) 0 (0)
Race
Asian 148 (12.6) 168 (14.3) 38 (19.0) 15 (15.0)
Black or African American 116 (9.8) 115 (9.8) 13 (6.5) 14 (14.0)
Multiple 26 (2.2) 30 (2.5) 9 (4.5) 6 (6.0)
White 867 (73.5) 844 (71.7) 139 (69.5) 62 (62.0)
Other 21 (1.8)  19 (1.6) 1 (0.5) 3  (3.0)
Ethnicity
Hispanic or Latino 259 (22.0) 242 (20.6) 58 (29.0) 24 (24.0)
Pneumococcal Risk Factors
1 Risk Factor 347 (29.4) 328 (27.9) 45 (22.5) 18 (18.0)
2 or More Risk Factors 100 (8.5) 81 (6.9) 3 (1.5) 1 (1.0)Pivotal Study
Confidential
Pneumococcal
serotypeV116 PCV20 GMT ratio
n GMT n GMT (95% CI)
3 1154 274.0 1161 176.7 1.55 (1.40, 1.72)
6A 1148 2,302.0 1153 2,972.5 0.77 (0.68, 0.88)
7F 1152 3,637.4 1158 3,429.9 1.06 (0.95, 1.18)
8 1155 2,501.3 1158 1,811.1 1.38 (1.25, 1.53)
10A 1161 3,893.4 1159 4,678.0 0.83 (0.75, 0.93)
11A 1145 3,232.6 1150 2,092.8 1.54 (1.39, 1.72)
12F 1160 2,641.2 1161 2,499.6 1.06 (0.92, 1.21)
19A 1159 2,136.1 1162 2,817.8 0.76 (0.69, 0.84)
22F 1147 3,874.5 1154 4,770.1 0.81 (0.72, 0.92)
33F 1154 13,558.9 1157 11,742.1 1.15 (1.01, 1.32)•V116 is noninferior to PCV20
for the 10 common serotypes.
•The lower bounds of the two -
sided 95% confidence
intervals (CIs) are greater
than 0.5 for all 10 common
serotypes.Primary immunogenicity objectiveV116 -003  Cohort 1: ≥50 years of age
V116 is noninferior to PCV20 for the 10 common serotypes
Postvaccination OPA GMT Ratios for Common Serotypes
0.5 1.0 2.0
GMT ratio log10 scale (V116/PCV20)
15Pivotal Study
Confidential
•V116 is superior to PCV20 for
10 of 11 unique serotypes in
V116.
•The lower bounds of the two -
sided 95% CIs are >2.0 for 10
of 11 unique serotypes in V116.
•For serotype 15C, the lower
bound of the 95% CI is 1.77.Primary immunogenicity objectivePostvaccination OPA GMT Ratios for Unique Serotypes
Pneumococcal
serotypeV116 PCV20 GMT ratio
n GMT n GMT (95% CI)
9N 1147 7,470.7 1150 1,640.4 4.55 (4.12, 5.04)
15A 1107 5,237.2 1102 1,589.0 3.30 (2.91, 3.74)
15C 1153 4,216.2 1158 2,072.3 2.03 (1.77, 2.34)
16F 1151 4,868.2 1153 846.3 5.75 (5.16, 6.41)
17F 1148 7,764.9 1156 460.4 16.86 (14.90, 19.09)
20A 1161 6,099.2 1155 631.1 9.66 (8.66, 10.79)
23A 1132 3,737.2 1104 461.5 8.10 (6.86, 9.55)
23B 1160 1,082.5 1160 107.3 10.09 (8.48, 12.00)
24F 1153 2,728.6 1130 70.5 38.71 (33.87, 44.25)
31 1153 3,132.5 1154 144.4 21.69 (18.68, 25.18)
35B 1153 8,527.8 1159 1,383.0 6.17 (5.59, 6.80)
GMT ratio log10 scale (V116/PCV20)1 0.5 2 4 8 16 32 64V116 -003  Cohort 1: ≥50 years of age
V116 is superior to PCV20 for 10 of 11 unique serotypes
16Pivotal Study
Superiority criteria met if the lower bound of the 95% CI is >2.0
Confidential
•V116 is superior to PCV20
for 10 of 11 unique
serotypes in V116.
•The lower bounds of the
2-sided 95% CIs are > 10
percentage points for 10
of 11 serotypes.Primary immunogenicity objectiveProportions of Participants With a ≥4-Fold Rise in OPA
Responses for Unique Serotypes64.7%
66.7%
83.4%
71.9%
75.8%
67.3%
78.9%
85.5%
80.5%
76.5%
60.0%19.9%
35.8%
74.2%
20.8%
9.5%
9.6%
36.8%
49.6%
6.3%
17.9%
6.8%
0%20%40%60%80%100%
9N 15A 15C 16F 17F 20A 23A 23B 24F 31 35B% of participants with a ≥4-fold rise
Unique serotype
V116 (N=1179) PCV20 (N=1177)44.7% 30.9% 9.2% 51.1% 66.3% 57.7% 42.2% 35.9% 74.2% 58.6% 53.2%% difference [V116 – PCV20]
p=0.665(40.7. 48.6) (25.8, 35.8) (5.6, 12.9) (47.1, 54.9) (62.8, 69.6) (54.2, 61.1) (37.6, 46.6) (32.1, 39.6) (71.1, 77.1) (54.8, 62.1) (49.6, 56.6) V116 -003  Cohort 1: ≥50 years of age
V116 is superior to PCV20 for 10 of 11 unique serotypes
17Pivotal Study
Confidential
V116 -003  Cohort 1: ≥50 years of age
V116 elicits robust cross reactive antibody responses to serotype 15B
18V116 includes serotype 15C
and elicited cross -reactive
immune responses to 15B0%20%40%60%80%100%
V116 (N=1179) PCV20 (N=1177)% of participants with a ≥4-fold rise in OPA
responsesSerotype 15BPivotal Study
PCV20 includes
serotype 15B64.6%
(61.3, 67.8) 64.7%
(61.4, 67.8)
Confidential
•V116 in participants 18 to 49
years of age immunobridges
to V116 in participants 50 to
64 years of age for the 21
serotypes in V116.
•The lower bound of the two -
sided 95% CIs is  >0.5 for all
21 serotypes in V116.Primary immunogenicity objective
Pneumococcal
serotypeV116
18–49 years
(N = 200)V116
50–64 years
(N = 589)GMT ratioa
(V116 18 –49 years/
V116 50–64 years)
n GMT n GMT (95% CI)
3 194 308.6 572 282.7 1.09 (0.90, 1.33)
6A 196 5,289.6 569 2,572.9 2.06 (1.61, 2.62)
7F 198 6,447.2 571 4,278.8 1.51 (1.23, 1.84)
8 197 4,516.0 571 3,004.7 1.50 (1.26, 1.79)
9N 197 17,283.2 570 8,791.4 1.97 (1.59, 2.43)
10A 197 6,808.1 575 4,382.6 1.55 (1.26, 1.92)
11A 196 5,871.6 564 3,785.8 1.55 (1.26, 1.91)
12F 196 6,150.4 574 3,561.2 1.73 (1.37, 2.17)
15A 184 11,319.2 550 5,901.2 1.92 (1.55, 2.37)
15C 195 10,194.0 570 5,708.0 1.79 (1.36, 2.35)
16F 193 8,877.0 571 5,720.0 1.55 (1.26, 1.91)
17F 194 16,070.6 568 10,068.0 1.60 (1.26, 2.02)
19A 198 2,773.2 574 2,374.6 1.17 (0.97, 1.40)
20A 197 13,150.0 575 7,562.7 1.74 (1.39, 2.18)
22F 198 9,299.6 568 4,683.6 1.99 (1.58, 2.49)
23A 192 8,848.7 561 4,739.5 1.87 (1.43, 2.44)
23B 198 2,140.1 575 1,420.9 1.51 (1.11, 2.04)
24F 197 4,137.6 570 3,047.2 1.36 (1.10, 1.67)
31 195 8,005.6 570 3,820.7 2.10 (1.63, 2.69)
33F 197 34,805.5 570 17,607.4 1.98 (1.52, 2.57)
35B 198 13,933.4 573 9,053.9 1.54 (1.26, 1.87)
GMT ratio log10 scale (V116 18 -49/V116 50 -64)1 0.5 2 4V116 -003:  Cohort 2: 18-49 years of age
V116 immunobridges to participants 50 -64 years of age for all 21 serotypes
19Pivotal Study
¹Weber Shandwick/KCR Research, 2020 / AMO 2019V116 -006V116 -006: A Phase 3 Clinical Study to Evaluate
the Safety, Tolerability, and Immunogenicity of
V116 in Pneumococcal Vaccine -Experienced
Adults 50 Years of Age or Older
20
Confidential
Cohort  1 : Prior PPSV23 only
N=300; Randomized 2:1 (V116:PCV15)V116 -006 Study Design
Visit
Time Day 1
Screening/vaccination1 3
V116Day 7 Day 90 Day 1802 4 5
Cohort  2 : Prior PCV13 only
N=300; Randomized 2:1 (V116:PPSV23)
Cohort  3 : Prior PCV15, PCV20, PCV13+PPSV23,
PCV15+PPSV23 or PPSV23+PCV13
N=100; Open -label V116Day 30
V116V116or
orPCV15
PPSV23
Prevaccination
Immunogenicity
(Day 1)
eVRC , solicited AEs
Serious and nonserious AEs Serious AEs
Postvaccination
Immunogenicity
(Day 30)
Participants used an electronic Vaccine Report Card ( eVRC ) to report solicited AEs Days 1 -5 postvaccination and other AEs through Day 30 postvaccination21Vaccine -experienced
Immunogenicity
assessment
Safety
assessment
Confidential
In adults ≥50 years:
To evaluate the serotype -specific opsonophagocytic activity
(OPA) geometric mean titers (GMTs) at 30 days postvaccination
for all serotypes included in V116V116 -006 Primary study objectivesVaccine -experienced
Primary safety Primary immunogenicity
•To evaluate the safety and tolerability of V116 as
assessed by the proportion of participants with adverse
events (AEs)
–Solicited injection site events Day 1 –5 postvaccination:
erythema, swelling, injection -site pain
–Solicited systemic events Days 1–5 postvaccination:
headache, myalgia, fatigue
–Serious vaccine -related events Day 1 through the duration of
participation in the study
22
Confidential
V116 -006 Participant Characteristics
Enrollment is balanced in each cohort and reflects the pneumococcal vaccination history
23Cohort 1 (prior PPSV23) Cohort 2 (prior PCV13) Cohort 3
V116
N=229PCV15
N=119V116
N=174PPSV23
N=85V116
N=105
Sex
Male 112 (48.9) 59 (49.6) 74 (42.5) 36 (42.4) 50 (47.6)
Female 117 (51.1) 60 (50.4) 100 (57.5) 49 (57.6) 55 (52.4)
Age ( yr)
50 to 64 48 (21.0) 25 (21.0) 80 (46.0) 39 (45.9) 17 (16.2)
≥65 181 (79.0) 94 (79.0) 94 (54.0) 46 (54.1) 88 (83.8)
Mean ±SD 68.7 ±7.5 69.0 ±7.1 65.5 ±7.8 65.4 ±6.6 71.0 ±7.6
Median (range) 69.0 (50 to 86) 69.0 (51 to 88) 66.0 (50 to 83) 65.0 (51 to 81) 71.0 (53 to 91)
Race
Asian 96 (41.9) 47 (39.5) 55 (31.6) 25 (29.4) 13 (12.4)
Black or African American 6 (2.6) 3 (2.5) 3 (1.7) 1 (1.2) 6 (5.7)
Multiple 2 (0.9) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.0)
White 125 (54.6) 69 (58.0) 116 (66.7) 59 (69.4) 85 (81.0)
Ethnicity
Hispanic or Latino 21 (9.2) 17 (14.3) 34 (19.5) 16 (18.8) 14 (13.3)
Time since last pneumococcal
vaccination
1 to 4 years 108 (47.2) 54 (45.4) 135 (77.6) 66 (77.6) 78 (74.3)
5 to 9 years 85 (37.1) 45 (37.8) 33 (19.0) 18 (21.2) 27 (25.7)
≥10 years 36 (15.7) 20 (16.8) 6 (3.4) 1 (1.2) 0 (0.0)Vaccine -experienced
Confidential
V116 -006 Cohort 1: ≥50 years of age who previously received PPSV23
V116 elicits comparable immune responses to PCV15; higher immune responses for serotypes unique to V116
2402,0004,0006,0008,000
8 9N 10A 11A 12F 15A 15C 16F 17F 20A 23A 23B 24F 31 35BObserved GMTUnique serotypes
V116 (N=229) PCV15 (N=119)02,0004,0006,0008,000
3 6A 7F 19A 22F 33FObserved GMTCommon serotypes
V116 (N=229) PCV15 (N=119)Vaccine -experienced
Confidential
V116 -006 Cohort 2: ≥50 years of age who previously received PCV13
V116 elicits comparable immune responses to PPSV23; higher immune responses for serotypes unique to V116
2502,5005,0007,50010,00012,500
3 7F 8 9N 10A 11A 12F 17F 19A 20A 22F 33FObserved GMTCommon serotypes
V116 (N=174) PPSV23 (N=85)02,5005,0007,50010,00012,500
6A 15A 15C 16F 23A 23B 24F 31 35BObserved GMTUnique serotypes
V116 (N=174) PPSV23 (N=85)Vaccine -experienced
Confidential
*Prior PCV13+PPSV23 [n=45], PCV15+PPSV23 [n=5], PPSV23+PCV13 [n=54], PCV15 [n=1], or PCV20 [n=0] 02,0004,0006,0008,000
3 6A 7F 8 9N 10A 11A 12F 15A 15C 16F 17F 19A 20A 22F 23A 23B 24F 31 33F 35BObserved GMT
05001,000
Serotype 3Observed GMTcohort 1 cohort 2 cohort 3V116 -006 Cohort 3: ≥50 years of age who previously received other pneumococcal vaccine(s)*
V116 is immunogenic in individuals who previously received a pneumococcal vaccine
26Participants who received V116Vaccine -experienced
Integrated Summary of Safety
27Integrated Analysis of Safety in the
Phase 3 Clinical Development Program
Confidential
V116 is well tolerated in adults ≥18 years of age with a safety profile comparable to
currently licensed pneumococcal vaccines
28a Only participants from V116 -005 vaccinated with V116 in the sequential group are included in the V116 group.
bControl  group includes participants vaccinated with PCV15, PCV20, or PPSV23
cAs determined by the investigator; all injection site adverse events are assessed as vaccine -related
d6 deaths in the V116 group in the Integrated Safety Summary; 7 deaths in the V116 group across the Phase 3 studies when the c oncomitant group from P005 is included. Adverse Event Summary
(V116 -003, V116 -004, V116 -005a, V116 -006) V116
(N=4,020)Control b
(N=2,018)
n (%) n (%)
With adverse events (Day 1 –30) 2695 (67.0) 1386 (68.7)
With vaccine -related adverse events (Day 1 -30)c2555 (63.3) 1297 (64.3)
Solicited 2516 (62.6) 1279 (63.4)
Unsolicited 313 (7.8) 123 (6.1)
with SAEs (Day 1 -Day 30)                        14                                      (0.3)                                    7                                       (0.3)
with vaccine -related SAEs (Day 1 -Day 30)                   2                                       (0.0)                                    0                                       (0.0)
with SAEs within 30 minutes postvaccination                                          1                                       (0.0)                                    0                                       (0.0)
Who diedd6                                       (0.1)                                    3                                       (0.1)
with vaccine -related deathsc0 (0.0) 0 (0.0)Integrated Safety
Solicited events include erythema, injection site pain, injection site swelling, fatigue, headache, and myalgia were solicite d from Day 1 through Day 5 postvaccination. Pyrexia was defined as
temperature ≥100.4 °F (38.0 C) solicited from Day 1 through Day 5 postvaccination.Frequency and intensity of solicited adverse events were comparable in V116 and control groups
Solicited adverse events by intensity (%)
0%10%20%30%40%50%60%
V116 Control V116 Control V116 Control V116 Control V116 Control V116 Control V116 ControlPotentially Life-threatening (Grade 4)
Severe (Grade 3)
Moderate (Grade 2)
Mild (Grade 1)
Injection site
erythemaInjection site pain Injection site
swellingFatigue Myalgia Headache PyrexiaIntegrated Safety
V116, n= 4,020      Control, n=2,018Majority of events were
≤3 days in duration
29
Phase 3 Supportive Studies
30V116 -007: V116 in Adults Living with HIV
V116 -005: V116 with Concomitant Quadrivalent Influenza Vaccine (QIV)
V116 -004: V116 Lot Consistency
Confidential
02,0004,0006,0008,00010,00012,00014,000
15A 15C 16F 23A 23B 24F 31 35BObserved GMTUnique serotypes
V116 + Placebo (N = 156) PCV15 + PPSV23 (N = 156)04,0008,00012,00016,00020,000
3 6A 7F 8 9N 10A 11A 12F 17F 19A 20A 22F 33FObserved GMTCommon serotypes
V116 + Placebo (N = 156) PCV15 + PPSV23 (N = 156)V116 -007: In adults living with HIV, V116 elicits comparable immune responses
to PCV15+PPSV23, & higher immune responses for unique serotypesAdults Living with HIV
31
Confidential
V116 -005: V116 elicits robust immune responses when administered
concomitantly with influenza vaccine
32•V116 administered
concomitantly with influenza
vaccine is noninferior to V116
administered sequentially
with influenza vaccine for 20
of 21 serotypes
•QIV administered
concomitantly is noninferior
to QIV administered
sequentially for 3 of 4 strains GMT ratio
Concomitant/Sequential
(95% CI)Pneumococcal
serotype
3 0.84 (0.72, 0.97)
6A 0.79 (0.66, 0.94)
7F 0.73 (0.63, 0.85)
8 0.71 (0.61, 0.82)
9N 0.67 (0.57, 0.79)
10A 0.76 (0.65, 0.91)
11A 0.64 (0.54, 0.75)
12F 0.76 (0.62, 0.94)
15A 0.71 (0.60, 0.85)
15C 0.71 (0.58, 0.87)
16F 0.69 (0.59, 0.81)
17F 0.73 (0.62, 0.86)
19A 0.75 (0.65, 0.85)
20A 0.74 (0.63, 0.87)
22F 0.77 (0.65, 0.91)
23A 0.78 (0.63, 0.96)
23B 0.56 (0.44, 0.72)
24F 0.72 (0.61, 0.86)
31 0.68 (0.56, 0.83)
33F 0.84 (0.70, 1.01)
35B 0.77 (0.67, 0.89)
0.25 0.5 1 2
GMT Ratio Log10 Scale
(Concomitant Group/Sequential Group)Concomitant Influenza
32
Confidential
V116 -004: V116 Immune responses were equivalent across 3 manufacturing lots
33Pneumococcal
serotypeV116 Lot 1 vs V116 Lot 2
n1=(502 -527), n2=(505 -533)V116 Lot 1 vs V116 Lot 3
n1=(502 -527), n2=(513 -533)V116 Lot 2 vs V116 Lot 3
n1=(505 -533), n2=(513 -533)
3
6A
7F
8
9N
10A
11A
12F
15A
15C
16F
17F
19A
20A
22F
23A
23B
24F
31
33F
35B
0.5 2 0.5 2 0.5 2 1 1 1
GMT Ratio Log10 Scale
Note: dashed lines indicate the margins for the equivalence testLot Consistency
Phase 3 Summary &
Conclusions
34
Confidential
V116 Phase 3 Clinical Development Summary
35In adults ≥18 years of age, who are pneumococcal vaccine -naïve and vaccine
experienced, with and without risk conditions:
•V116 elicits robust immune responses to all 21 serotypes contained in the vaccine
•V116 is noninferior to PCV20 for all common serotypes and superior to PCV20 for 10 of 11
serotypes unique to V116 in pneumococcal vaccine -naïve adults ≥50 years of age.
•V116 is immunogenic in pneumococcal vaccine experienced adults , regardless of the prior
vaccine received
•V116 is immunogenic when administered concomitantly with inactivated influenza vaccine .
•V116 is well -tolerated  with a safety profile generally comparable to currently licensed
pneumococcal vaccines.
V116 is the first adult specific PCV with the potential for broad public health impact through the prevention of invasive dis ease
and pneumonia due to S. pneumoniae .
Confidential
Thank you
Slide is intentionally blank

Summary: V116: An Investigational Adult Specific Pneumococcal  Conjugate Vaccine Key Results from the Phase 3 Clinical Development Program ACIP Meeting, 29 -Feb -2024 Heather Platt, M.D., on behalf of the V116 team Distinguished Scientist, Global Clinical Development Merck Research Laboratories Merck & Company, Inc. Presentation Rationale for Development of V116  Overview of V116 Adult Clinical Development Program  Immunogenicity Results •Vaccine naïve adults ≥18 years of age •Vaccine experienced…


05 Pneumococcal Moro 508

National Center for Emerging and Zoonotic Infectious Diseases
Post -licensure safety surveillance of 20 -valent
pneumococcal conjugate vaccine (PCV20)
among U.S. adults in the Vaccine Adverse
Event Reporting System (VAERS)
Pedro L. Moro, MD, MPH
Immunization Safety Office
Division of Healthcare Quality Promotion Centers for Disease Control and Prevention (CDC)
Advisory Committee on Immunization Practices (ACIP)
February 29, 2024
Disclaimer
The findings and conclusions in this presentation are
those of the author and do not necessarily represent the official position of the CDC
The use of product trade names is for identification purposes only
2
Background on pre -l icensure safety of 20 -valent
pneumococcal conjugate vaccine (PCV20)
Adverse events following PCV20 reported to the Vaccine
A
dverse Event Reporting System (VAERS)
Adverse events of special interest: Guillain -Barr é
Syndrome (GBS)
Summary
3Topics
Background: Pre -licensure clinical trials PCV20
1 Pfizer’s Adult and Pediatric Clinical Trial Programs for 20 -Valent Pneumococcal Conjugate Vaccine Presented at IDWeek  2020. October 21, 2020.
2 Kobayashi M, Farrar JL, Gierke R, et al. Use of 15 -Valent Pneumococcal Conjugate Vaccine and 20 -Valent Pneumococcal Conjugate V accine Among U.S. Adults: Updated Recommendations of the Advisory
Committee on Immunization Practices — United States, 2022. MMWR Morb  Mortal Wkly  Rep 2022;71:109 –117. DOI: http://dx.doi.org/10.15585/mmwr.mm7104a1
3 Prevnar20 vaccine insert https://www.fda.gov/vaccines -blood -biologics/vaccines/prevnar -20 Pre-licensure clinical trial data of PCV20 in adults has been reassuring
Six randomized controlled trials in adults aged ≥ 18 years, which included more than
6,000 participants1,2
Most common adverse reactions were injection site pain, muscle pain, fatigue, headache, and joint pain
2,3
Serious adverse events (SAEs) balanced among vaccinees and controls2
No SAEs or deaths considered to be related to study vaccines3
No cases of Guillain -Barré Syndrome (GBS) identified in prelicensure studies2,3
4
Introduction
June 8, 2021 –  PCV20 approved for adults aged ≥ 18 years
by the FDA
October 20, 2021 – ACIP recommendation
PCV20 for adults aged ≥65
PCV20 for adults aged 19– 64 years with underlying medical
conditions
FDA: Food and Drug Administration
ACIP: Advisory Committee on Immunization Practices
5
Objectives
Describe the safety profile of reports submitted to the
V
accine Adverse Event Reporting System (VAERS) following
PCV20 in
Adults aged ≥65 years
Adults aged 19 –64 years
6
VAERS
Strengths
National data
Accepts reports from anyone
Rapidly detects safety signals
Can detect rare adverse events
Data available to publicLimitations
Reporting bias
Inconsistent data quality and
completeness
Lack of unvaccinated comparison group or denominator
Generally cannot assess causality
•VAERS accepts all reports from all reporters without making judgments on
causality or judging clinical seriousness of the event
•As a hypothesis generating system, VAERS identifies potential vaccine safety concerns that can be studied in more robust data systems
7
Methods – 1: PCV20
Searched VAERS database for U.S. PCV20 reports during:
•October 21, 2021 through December 31, 2023 for adults aged ≥ 19 years
(19– 64 years and ≥ 65 years)
Signs and symptoms of AEs coded using Medical Dictionary for Regulatory
Activities (MedDRA)1 Preferred Terms (PTs)
•PTs are not mutually exclusive
•A single report may be assigned more than one PT
Review of serious2 reports and medical records; categorized main diagnosis
in a MedDRA system organ class
Case definitions for AESIs: Guillain -Barré Syndrome3
1  https://www.meddra.org/   ; 2 Based on the Code of Federal Regulations 21 CFR 600.80 ; 3Sejvar JJ, et al.  Brighton Collaboration GBS Working Group. Guillain -Barré syndrome and
Fisher syndrome: case definitions and guidelines for collection, analysis, and presentation of immunization safety data. Vacc ine. 2011 Jan 10;29(3):599 -612. doi:
10.1016/j.vaccine.2010.06.003. Epub 2010 Jun 18. PMID: 206004918
Methods – 2: PCV20
Reporting rates
•Use of doses distributed of PCV20 in the United States during 2022 a nd
2023 (20,
579,720 doses)
Empirical Bayesian data mining (FDA)*
•Used to detect disproportional reporting for the entire post marketing
pe
riod for each product
•Identifies adverse events reported more frequently than expected afterv
accine of interest compared with other vaccines in the VAERS database
•Analysis by age groups and se rious reports.**
9*The presence of disproportionality may not  suggest a safety signal.  Conversely, the absence of disproportionality does not  confirm the absence of a safety signal
nor negate a signal detected by other methods.
**A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that meets any of the following criteria: 1. Resul ts in death; 2. Is life -threatening;
3.Re
quires inpatient hospitalization or prolongation of existing hospitalization; 4. Results in persistent or significant disab ility/incapacity; 5. Is a congenital
anomaly/birth defect. [FDA regulatory definition; U.S. Code of Federal Regulations, 21 CFR 600.80. Postmarketing reporting of adverse experiences (2014).
Available at: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=600.80 ]
PCV20 reports to VAERS, October 2021 –December 2023
19 – 64 years ≥ 65 years ≥ 19 years All2
Characteristics1                      N (%) N (%) N (%) N (%)
Total reports 798 1,178 1,976 2,393
Female 582 (72.9) 846 (71.8) 1,428 (72.3) 1,598 (66.7)
Male 212 (26.6) 330 (28.0) 542 (27.4) 680 (28.4)
Unknown sex 4 (0.5) 1 (0.1) 5 (0.3) 115 (4.8)
Serious reports349 (6.1) 70 (5.9) 119 (6) 149 (6.2)
Deaths 2 (0.3) 9 (0.8) 11 (0.6) 20 (0.8)
Median age [IQR] in years 54 [45,60] 69 [66,75] 65 [56,70]
Median onset interval [IQR] in days 1 [0,2] 1 [0,2] 1 [0,2] 1 [0,1]
Received PCV20 alone 438 (54.9) 711 (60.4) 1,149 (58.1) 1,412 (59.0)
3 Based on the Code of Federal Regulations if one of the following is reported: death, life -threatening illness, hospitalization o r prolongation of hospitalization
                    or permanent disability 101 U.S. primary reports (foreign reports excluded) ; 2Includes reports in adults aged ≥19 years and 176 reports in persons aged 0 -18 years and 241 reports of unknown age
Most common signs and symptoms1 in reports to VAERS following
PCV20 in adults aged 19 –64 years, October 2021– December 2023
PCV20  Non- serious (N=749) N (%)
Injection site reaction 227 (30)
Pain 129 (17)
Erythema 117 (16)
Fever 103 (14)
Pain in extremity 90 (12)
Peripheral swelling 77 (10)
Headache 59 (8)
Skin warm 59 (8)
Fatigue 56 (7)
Arthralgia 52 (7)
1 Coded using the MedDRA  Preferred Terms;  more than one MedDRA  Preferred Term  may be assigned to a single report (i.e., not mutually exclusive) 11PCV20  Serious (N=49) N (%)
Fever 14 (29)
Dyspnea 12 (25)
Condition aggravated 10 (20)
Cough 10 (20)
Pain 10 (20)
Nausea 9 (18)
Pain in extremity 8 (16)
Dizziness 7 (14)
Fatigue 7 (14)
Headache 7 (14)
Most common signs and symptoms1 in reports to VAERS following
PCV20 in adults aged ≥65 years, October 2021 –December 2023
PCV20  non- serious (N=1,108) N (%)
Injection site reaction 417 (35)
Pain 180 (15)
Pain in extremity 162 (14)
Erythema 158 (13)
Fever 135 (12)
Peripheral swelling 103 (9)
Rash 99 (8)
Fatigue 96 (8)
Headache 88 (7)
Pruritus 78 (7)
1 Coded using the MedDRA  Preferred Terms;  more than one MedDRA  Preferred Term  may be assigned to a single report (i.e., not mutually exclusive) 12PCV20 Serious (N=70) N (%)
Pain 14 (20)
Asthenia 13 (19)
Gait disturbance 11 (16)
Guillain Barre Syndrome 11 (16)
Dyspnea 8 (11)
Fatigue 8 (11)
Fever 8 (11)
Chest pain 7 (10)
Death 7 (10)
Dysphagia 7 (10)
Empirical Bayesian data mining (as of January 26, 2024)
Disproportional reporting observed for:
•PT for “Guillain -Barré Syndrome” when limited to serious reports
(EB05=3.6)1
•When not limited to serious reports EB05=1.87
131 EB05 = Empirical Bayesian data mining threshold for statistical alert; alert considered if EB05 >2.0
Reports to VAERS of Guillain Barre Syndrome after PCV20 vaccination
among adults aged ≥19 years (as of December 31, 2023)
11 verified reports of Guillain Barré Syndrome2
•Median age (range), years: 66 years (46 -79 y ears)3
•Median time to onset (range), days: 14 days (0 -23)
•4 males, 7 females
•All verified reports met Brighton Collaboration criteria for
G
BS:
–2 were Brighton level 1, 6 were level 2 and 3 were level 3
•Other vaccines during same visit (5 of 11):
– Two RZV (Shingrix)
– One F luad  quadrivalent
– One bivalent mRNA COVID - 19 (Pfizer), HD -IIV4, RSV ( Arexvy )
– One Tdap (Boostrix)Preliminary reports of Guillain
Barre Syndrome (N=20)
Under
review1
(n=4)
Excluded
based upon
chart review
(n=5)
Verified GBS by chart review (n=11) 1 Awaiting medical records
2 One patient had a norovirus infection 1 -2 days before neurological symptoms
3 No GBS reports in persons aged <19 years 14
Reporting rate for GBS after PCV20, 2022 –2023
Reporting rate: 0.5 cases per million doses distributed or 0.9 cases per
100,000 person- years (background rate 1.72 cases per 100,000 persons -
years) 1
1Gubernot D, et al. U.S.  Population- B ased background incidence rates of medical conditions for use in safety assessment of
CO VID -19 vaccines.  V accine.  2021;  39:  3666–3677.
15
Summary
VAERS received 1,976 reports after PCV20 in adults during October 2021–
December 2023
•798 in adults aged 19– 64 years; 93.9% non- serious
•1,178 in adults aged ≥65 years; 94.1% non- serious
Most commonly reported adverse events were injection site (e.g. injection site erythema) and systemic reactions (e.g. fever, headache); consistent
with findings from pre -licensure studies
16
Summary (continued)
Disproportionate reporting for Guillain -Barré Syndrome (GBS) identified in
VAERS after PCV20 vaccine (11 verified GBS cases in adults)
Potential safety signals detected in VAERS need to be evaluated in more robust
population -based active systems such as the Vaccine Safety Datalink (VSD) or
Center for Medicaid Services (CMS)

Separate studies currently in progress in the VSD (CDC) and CMS (FDA) to assess PCV20 vaccine safety
CDC and FDA will continue to closely monitor the safety of PCV20
17
Acknowledgements
CDC Immunization Safety Office
•VAERS Team
•Clinical Immunization Safety Assessment (CISA) Project
Food and Drug Administration
•Office of Biostatistics and Pharmacovigilance, Center for Biologics Evaluation
an
d Research
Butantan  In stitute, Sao Paulo, Brazil
18
For more information, contact CDC
1-800- CDC- INFO (232 -4636)
TTY:  1 -888- 232- 6348    www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
Photo credit: James Gathany
(https://wwwn.cdc.gov/phil/
Details.aspx?pid=8876)

Summary: National Center for Emerging and Zoonotic Infectious Diseases Post -licensure safety surveillance of 20 -valent  pneumococcal conjugate vaccine (PCV20)  among U.S. adults in the Vaccine Adverse  Event Reporting System (VAERS) Pedro L. Moro, MD, MPH Immunization Safety Office Division of Healthcare Quality Promotion Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) February 29, 2024 Disclaimer The findings and conclusions in this presentation…


05 Pneumococcal Forshee 508

FDA CBER:
Safety Assessment of 20- valent Pneumococcal Conjugate
Vaccine (PCV20)
ACIP February 2024
Richard Forshee, PhD
Office of Biostatistics and Pharmacovigilance
Center for Biologics Evaluation and Research
US Food and Drug Administration
2
Disclaimer
•The BEST Initiative and its studies are funded by the U.S.
Food and Drug Administration (FDA)
•There are no potentially conflicting relationships to disclose
•The findings and conclusions in this presentation are those of the authors and do not necessarily represent the official position of FDA, the Centers for Medicare & Medicaid Services, or Acumen, LLC
3
•Acute Myocardial Infarction
•Myocarditis/Pericarditis
•Anaphylaxis
•Atrial Fibrillation
•Bell’s Palsy
•Cardiomyopathy; Heart Failure
•Cellulitis and Infection
•Cholecystitis or Cholelithiasis
•Guillain -Barré syndrome
•Immune Thrombocytopenia
•Thrombocytopenia
•Transient Ischemic AttackIs there an elevated risk for the listed health outcomes*
following PCV20 vaccination?
* The list of health outcomes were identified via literature review
4
Near Real -Time Monitoring: Medicare Fee -for-Service (FFS)
Population (Age ≥ 65 years)
DesignConcurrent Comparator Cohort Design1 for Near Real -Time Sequential Analysis
Self-controlled case series planned to verify detected signals
Data Sources Centers for Medicare & Medicaid Services (CMS) – Shared Systems Data (SSD)
Study  PopulationMedicare FFS beneficiaries (age ≥ 65 years) receiving one dose of PCV 15 or PCV 20
on or after the licensing date for the product-Two product populations analyzed separately
Study PeriodLicensing date (PCV 15 = July 16, 2021 and PCV 20 = July 1, 2021) through the end of
each calendar month (most recent update through November 30, 2023)
Health OutcomesThe 12 pre-specified health outcomes identified by claims algorithms and monitored
within the follow -up window for each vaccinated beneficiary
1. Klein, N.P ., et al., Surveillance for Adverse Events After COVID -19 mRNA Vaccination. JAMA, 2021. 326(14): p. 1390- 1399.
5
Near Real -Time Monitoring: Medicare Fee -for-Service (FFS)
Population (Age ≥ 65 years)
Statistical
Analyses•Descriptive and Sequential analyses were performed monthly
•Bayesian Poisson Regression was used to estimate the posterior distribution of incidence rate ratio (IRR) between pre-specified post -vaccination risk and comparison
windows for each outcome
•Age, Sex, Immunocompromised Conditions*, Concomitant Influenza Vaccination**, and Months Post -Surveillance Start Date were included as
adjustment covariates
•Adjustment for claims delay was made
•Safety signal was assessed by evaluating if:
•The 95% Credible Interval (CI) exceeds 1 –Weak Signal
•The 98% Credible Interval (CI) exceeds 1 – Strong Signal
* Immunocompromised conditions was identified using administrative codes indicating presence of immunocompromising conditions  or use of immunosuppressive therapies2
** Concomitant influenza vaccination is defined as seasonal influenza vaccination events that happened on or within 42 days prio r to PCV 20 vaccination date
2. Greenberg JA, et al., Validation of a Method to Identify Immunocompromised Patients with Severe Sepsis in Administrative Data bases. Ann Am Thorac  Soc. 2016;13(2):253- 258.
6
Uptake of PCV15 or PCV20 Vaccines in the Medicare FFS 65+
years Population; Monthly (top) and Cumulative (bottom) Counts*
* Data cut: 11/30/2023Total PCV 15 uptake:    53,018
Total PCV 20 Uptake: 2,832,555
7
Descriptive Characteristics of PCV 20 Vaccinees (N = 2,832,555)
Beneficiary Characteristics Number of
Vaccinees% of
Vaccinees
Race/Ethnicity
 Asian 70,416 2.49%
 Black 155,878 5.50%
 Hispanic 41,611 1.47%
 Alaska Native/American Indian 6,964 0.25%
 White 2,410,290 85.09%
 Other 57,163 2.02%
 Missing/Unknown 90,233 3.19%
Age (years)
 65-69 1,242,140 43.85%
 70-74 599,077 21.15%
 75-79 461,978 16.31%
 80-84 291,753 10.30%
 85-89 154,499 5.45%
 90-94 64,176 2.27%
 95+ 18,932 0.67%Beneficiary Characteristics Number of
Vaccinees% of
Vaccinees
Sex
 Female 1,614,235 56.99%
 Male 1,218,320 43.01%
Urban/Rural
 Urban 2,375,807 83.88%
 Rural 455,787 16.09%
 Missing/Unknown 961 0.03%
Immunocompromised Status
 Yes 144,510 5.10%
 No 2,688,045 94.90%
Medicare -Medicaid Dual Eligibility Status**
 Yes 264,266 9.33%
 No 2,568,289 90.67%
Concomitant Influenza Vaccination***
 Yes 496,007 17.51%
 No 2,336,548 82.49%
* Data cut: 11/30/2023
** Medicare- Medicaid dual eligibility status is defined as ever being dual eligible within the 3 months prior to the vaccination  date
*** Concomitant influenza vaccination is defined as seasonal influenza vaccination events that happened on or within 42 days prior to PCV 20 vaccination date
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Outcome Count and Incidence Rate (IR) among PCV20 vaccinated population*
Health Outcome Risk
Window**
(days)Comparison
Window
(days)Total
N (IR***)Risk Window
N (IR****)Comparison
Window
N (IR****)
Acute Myocardial Infraction 1-28 29-56 3,274 (970) 1,699 (965) 1,575 (975)
Myocarditis/Pericarditis 1-21 22-42 80 (31) 43 (32) 37 (29)
Anaphylaxis 0-1 3-16 25 (20) - (26) - (20)
Atrial Fibrillation 1-42 43-84 17,925 (3,879) 9,709 (3,908) 8,216 (3,845)
Bell’s Palsy 1-42 43-84 1,090 (207) 624 (220) 466 (191)
Cardiomyopathy; Heart
Failure1-42 43-84 16,263 (3,503) 8,778 (3,518) 7,485 (3,486)
Cellulitis and Infection 1-7 8-14 3,187 (3,548) 1,660 (3,685) 1,527 (3,410)
Cholecystitis or Cholelithiasis 1-28 29-56 665 (195) 323 (182) 342 (210)
Guillain -Barré Syndrome 1-42 43-84 29 (6) - (8) - (4)
Immune Thrombocytopenia 1-42 43-84 49 (10) 30 (11) 19 (8)
Thrombocytopenia 1-28 29-56 3,552 (1,053) 1,787 (1,015) 1,765 (1,093)
Transient Ischemic Attack 1-28 29-56 621 (182) 318 (179) 303 (186)
* Data cut: 11/30/2023, # of PCV 20 total uptake: 2,832,555
** Risk and comparison windows are defined as the number of days post vaccination *** All IRs expressed as IR per 100,000 person -years
**** For the health outcome that has risk or comparison windows count less than 11, the counts for both windows are masked by  “-”
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IRR between Risk and Comparison Windows with 95% and 98% CI among
PCV20 Vaccinated Population*
Health Outcome IRR** 95% CI 98% CI
Acute Myocardial Infraction 0.95 (0.89, 1.02) (0.87, 1.03)
Myocarditis/Pericarditis 1.05 (0.69, 1.64) (0.64, 1.77)
Anaphylaxis 1.11 (0.31, 3.12) (0.22, 3.78)
Atrial Fibrillation 0.98 (0.95, 1.01) (0.95, 1.02)
Bell’s Palsy 1.13 (1.00, 1.29) (0.97, 1.32)
Cardiomyopathy; Heart Failure 0.96 (0.93, 0.99) (0.92, 1.00)
Cellulitis and Infection 1.06 (0.99, 1.14) (0.97, 1.15)
Cholecystitis or Cholelithiasis 0.85 (0.73, 1.00) (0.71, 1.03)
Guillain -Barré Syndrome 2.19 (0.97, 5.42) (0.82, 6.50)
Immune Thrombocytopenia 1.35 (0.75, 2.50) (0.67, 2.78)
Thrombocytopenia 0.89 (0.83, 0.95) (0.82, 0.97)
Transient Ischemic Attack 0.94 (0.80, 1.11) (0.78, 1.14)
* Data cut: 11/30/2023, # of PCV 20 total uptake: 2,832,555** IRR = Incidence rate ratioNo statistically
significant elevated
risk was detected
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Estimated Posterior Distributions of IRR from Sequential Analyses at
Different Data Cuts – Myocarditis/Pericarditis
Median of the Posterior Distribution
(IRR = 1.05)
IRR = 1, meaning no rate difference
in the health outcome between risk and comparison windows
IRR posterior distribution from Bayesian model using data through November 2023
11
Estimated Posterior Distributions of IRR from Sequential
Analyses at Different Data Cuts – All  Health Outcomes

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Summary
•Incidence rates post PCV 20
•Incidence rates for Myocarditis/Pericarditis, Anaphylaxis, Guillain -Barré
Syndrome and Immune Thrombocytopenia are less than  100 cases per 100,000
person -years
•Signal detection
•The estimated IRRs and CIs did not identify statistically significant risk
elevation following PCV 20 vaccination for any of the outcomes (no significant
evidence that IRR > 1)
•We continue to monitor and evaluate the health outcomes
Note: Summary based on results from data cut: 11/30/2023
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Limitations for Sequential Monitoring
•Statistically significant results may appear and disappear from
month to month due to use of Bayesian methods.
•Events were not chart- confirmed and the Positive Predictive
Value (PPV) for some outcomes are likely low, e.g. The PPV for
Bell’s Palsy was 12.66% and the PPV for ITP was 4.00% in a
recent study.
•Residual confounding may still exist given the limited number
of variables being adjusted in the regression model
•Large uncertainty of incidence rate ratios for certain outcomes
•Small number of events, wide credible intervals
14
Future Planning
•Active monitoring to continue monthly
•End of surveillance analysis may be performed using the self- controlled
case series (SCCS) method for each outcome where there is sufficient
sample size for a powered analysis
15
Summary of Evidence
•No GBS signal in clinical trials
•GBS signal for PCV20 in VAERS
•Currently no GBS signal in Medicare sequential
monitoring. Monitoring is ongoing.
•Significant uncertainty because of the small number of cases observed
•Limitations in VAERS and Medicare studies
16
Acknowledgements
FDA CBER
Xinyi Ng
Richard ForsheeWhitney SteeleBarbee Whitaker
www.bestinitiative.orgAcumenYue WuMao HuJing WangNatalie SistoYoganand ChillarigeBing LyuJianfeng ZhuangPurva ShahWenxuan ZhouHolin ChenSamikshya SiwakotiYenlin LaiCenters for Medicare
and Medicaid Services (CMS)

Summary: FDA CBER:  Safety Assessment of 20- valent Pneumococcal Conjugate  Vaccine (PCV20) ACIP February 2024 Richard Forshee, PhD Office of Biostatistics and Pharmacovigilance Center for Biologics Evaluation and Research US Food and Drug Administration 2 Disclaimer •The BEST Initiative and its studies are funded by the U.S.  Food and Drug Administration (FDA) •There are no potentially conflicting relationships to disclose •The findings and conclusions in this presentation are those of the authors and…