02 RSV Adults Gurtman 508

Breakthroughs that change patients’ lives 1 ConfidentialAlejandra Gurtman, MD, FIDSA
Presentation to ACIPJune 21, 2023RSVpreF Older Adults
Clinical Development Program
Updates
2 Confidential WRDM Worldwide Medical & SafetyABRYSVOTM(Respiratory Syncytial Virus Vaccine)
FDA Approval on 5/31/2023RSVpreF Older Adult
–Clinical Development Program Updates
Indication
Active immunization for the prevention of lower respiratory tract disease (LRTD)
caused by respiratory syncytial virus (RSV) in individuals 60 years of age and older
Additional Clinical Trial Data
•RENOIR –End-of -Season 1 and Mid-Season 2 analyses
•RSVpreF/influenza vaccine coadministration study
3 Confidential WRDM Worldwide Medical & SafetyRENOIR
–Phase 3 safety and efficacy study in adults ≥ 60 years of age
38,863 participants enrolled
Healthy or with stable chronic conditions
Randomized 1:1 to receive
RSVpreF 120 μg or placebo
Stratified by age group
60−69 years |70−79 years |≥ 80 years

4 Confidential WRDM Worldwide Medical & SafetyDay 1 D ay 7 Month 1 Month 6 End Season 1 Start Season 2 End Season 2RENOIR Study Design
Reactogenicity
Subset
(n = 7,169)Local Reactions
Systemic Events
Immunogenicity
Subset
(n = 1,050)All Participants
(N = 36,127) Safety: SAEs, NDCMCsSafety: Unsolicited AEs
Weekly active surveillance for acute respiratory symptoms Weekly active surveillance for acute respiratory symptoms
e e
AE, adverse event; NDCMC, newly diagnosed chronic medical condition; SAE, serious adverse event
Day 1 Day 7 Month 1 Month 6 End Season 1 Start Season 2 End Season 2RENOIR Study Design
Reactogenicity
Subset
(n = 7,169)Local Reactions
Systemic Events
Immunogenicity
Subset
(n = 1,050)All Participants
(N = 36,127) Safety: SAEs, NDCMCsSafety: Unsolicited AEs
Weekly active surveillance for acute respiratory symptoms Weekly active surveillance for acute respiratory symptoms
e e
Season 1 Mid-Season 2
5 Confidential WRDM Worldwide Medical & SafetyAE, adverse event; NDCMC, newly diagnosed chronic medical condition; SAE, serious adverse event
Day 1 Day 7 Month 1 Month 6 End Season 1 Start Season 2 End Season 2RENOIR Study Design
Reactogenicity
Subset
(n = 7,169)Local Reactions
Systemic Events
Immunogenicity
Subset
(n = 1,050)All Participants
(N = 36,127) Safety: SAEs, NDCMCsSafety: Unsolicited AEs
Weekly active surveillance for acute respiratory symptoms Weekly active surveillance for acute respiratory symptoms
e e
Season 1 Mid-Season 2
Average Time
since VaccinationNorthern and Southern Hemispheres Northern Hemisphere
13.9 months
6 Confidential WRDM Worldwide Medical & SafetyAE, adverse event; NDCMC, newly diagnosed chronic medical condition; SAE, serious adverse event
Efficacy against RSV -LRTD
–Demonstrated through Mid-Season 2 Analysis
Number of Events
RSVpreF Placebo
Season 1 (N = 36,127) 15 43
Mid-Season 2 (n = 20,019) 23 4565.1%
48.9%
0 20 40 60 80 100
Vaccine Efficacy (%, 95% CI)RSV-LRTD with ≥ 2 symptoms
Mid-Season 2 includes Northern Hemisphere only (US, Canada, Finland) through January 31, 2023Number of Events
RSVpreF Placebo
Season 1 (N = 36,127) 2 18
Mid-Season 2 (n = 20,019) 3 1488.9%
78.6%
0 20 40 60 80 100
Vaccine Efficacy (%, 95% CI)RSV-LRTD with ≥ 3 symptoms
7 Confidential WRDM  Worldwide Medical & Safety
Persistent VE against RSV -LRTD with ≥ 3 Symptoms
through Mid-Season 2
Cumulative Events
RSVpreF 0 1 1 1 2 3 3 4 5
Placebo 0 5 12 15 17 20 24 27 32
40
30
20
10
0
1 74 119 186 235 306 353 417 519
Study DayCases
RSVpreFPlacebo
8 WRDM  Worldwide Medical & SafetyRSV-LRTD, lower respiratory tract disease due to RSV; RSV, respiratory syncytial virus; VE, vaccine efficacy.

9 WRDM  Worldwide Medical & SafetyPersistent VE against RSV -LRTD with ≥ 2 Symptoms
through Mid-Season 2
Cumulative Events
RSVpreF 0 5 8 10 12 18 24 31 38 38
Placebo 0 13 23 31 40 45 57 72 87 88
100
60
40
20
0
1 64 119 176 233 293 349 404 519
Study Day467Cases80
RSVpreFPlacebo
RSV-LRTD, lower respiratory tract disease due to RSV; RSV, respiratory syncytial virus; VE, vaccine efficacy.
10 Confidential WRDM Worldwide Medical & SafetyAdverse Events, by Category, from Vaccination through 1 -Month
Follow Up Visit and through Data Cutoff (31Jan2023): Safety Population
Adverse Event CategoryRSVpreF
N =18,575Placebo
N= 18,288
n(%) (95% CI) n(%) (95% CI)
From Vaccination through 1-Month Fol low-Up Visit
Any Event 1,976 (10.6) (10.2, 11.1) 1,897 (10.4) (9.9, 10.8)
Related 259 (1.4) (1.2, 1.6) 178 (1.0) (0.8, 1.1)
Immed iate AE 37 (0.2) (0.1, 0.3) 33 (0.2) (0.1, 0.3)
Severeor life-threatening 102 (0.5) (0.4, 0.7) 95 (0.5) (0.4, 0.6)
From Vaccination through 31Jan2023
NDCMC 806 (4.3) (4.1, 4.6) 825 (4.5) (4.2, 4.8)
SAE 790 (4.3) (4.0, 4.6) 746 (4.1) (3.8, 4.4)
Related SAE 3 (<0.1) (0.0, 0.1) 0 (0.0, 0.0)
AE leading to withdrawal 12 (<0.1) (0.0, 0.1) 11 (<0.1) (0.0, 0.1)
100 (0.5) (0.4, 0.7) 104 (0.6) (0.5, 0.7) A
E leading to death
Any reactogenicity reported as adverse events (from either reactogenicity subset or non- reactogenicity subset) during the specif ied time period are included in this table.
Immediate AE refers to an AE reported in the 30- minute post -vaccination observation period.
AE, adverse event; NDCMC, newly diagnosed chronic medical condition; SAE, serious adverse event.
11 Confidential WRDM Worl dwide Medical & SafetyAdverse Events, by Category, from Vaccination through 1 -Month
Follow Up Visit and through Data Cutoff (31Jan2023): Safety Population
Adverse Event CategoryRSVpr
eF
N =18,575Placebo
N= 18,288
n(%) (95% CI) n(%) (95% CI)
From Vaccinati on through 1 -Month Follow -Up Visit
Any Event 1,976 (10.6) (10.2, 11.1) 1,897 (10.4) (9.9, 10.8)
Related 259 (1.4) (1.2, 1.6) 178 (1.0) (0.8, 1.1)
Immediate AE 37 (0.2) (0.1, 0.3) 33 (0.2) (0.1, 0.3)
Severe or life -threatening 102 (0.5) (0.4, 0.7) 95 (0.5) (0.4, 0.6)
From Vaccinati on through 31Jan2023
NDCMC 806 (4.3) (4.1, 4.6) 825 (4.5) (4.2, 4.8)
SAE 790 (4.3) (4.0, 4.6) 746 (4.1) (3.8, 4.4)
Related SAE 3 (<0.1) (0.0, 0.1) 0 (0.0, 0.0)
AE leading to wi thdrawal 12 (<0.1) (0.0, 0.1) 11 (<0.1) (0.0, 0.1)
AE leading to death 100 (0.5) (0.4, 0.7) 104 (0.6) (0.5, 0.7)
Any reactogenicity reported as adverse events (from either reactogenicity subset or non- reactogenicity subset) during the specif ied time period are included in this table.
Immediate AE refers to an AE reported in the 30- minute post -vaccination observation period.
AE, adverse event; NDCMC, newly diagnosed chronic medical condition; SAE, serious adverse event.
12 WRDM  Worldwide Medical & SafetyRSVpreF/influenza vaccine coadministration study
13 WRDM  Worldwide Medical & SafetyPhase 3 Study Design and Key ProceduresRSVpreF/SIIV Coadministration in Adults ≥ 65 Years of Age
•Placebo-controlled, double-blind study
•Assessing safety and immunogenicity
(non- i
nferiority)
•Australia (31 sites)
•~1,400 healthy participants ≥ 65 years of age
•Randomized 1:1
•SIIV: Fluad Quadrivalent
•Tim
eframe: April 13, 2022 –October  12, 2022RSVpreF
Placebo
Placebo
RSVpreFRSVpreF/influenza vaccine
coadministration
Coadministration Group (n ≈ 700)
Sequential Administration Group (n ≈ 700)Visit 3 Visit 2 Visit 1
(~ 1 month after Visit 2) (~ 1 month after Visit 1)
SIIV, seasonal inactivated influenza vaccineSIIV
SIIV
14 WRDM  Worldwide Medical & SafetyCoadministration
(RSVpreF + SIIV) / Placebo
(N = 703)
n (%)Sequential Administration
(Placebo + SIIV) / RSVpreF
(N = 696)
n (%)Total
(N = 1,399)
n (%)
Sex
Female 398 (56.6) 372 (53.4) 770 (55.0)
Age at Visit 1 (years)
Mean (SD) 70.7 (4.7)                                  70.7 (4.7) 70.7 (4.7)
Median 70.0 70.0 70.0
Min, max (65, 91) (65, 88) (65, 91)
Age group at Visit 1
65-74 years 567 (80.7) 559 (80.3) 1126 (80.5)
≥ 75 years 136 (19.3) 137 (19.7) 273 (19.5)
Race
White 669 (95.2) 665 (95.5) 1,334 (95.4)
Asian 22 (3.1) 21 (3.0) 43 (3.1)
Multiracial 4 (0.6) 1 (0.1) 5 (0.4)
Other 4 (0.6) 4 (0.5) 8 (0.6)
Not reported or unknown 4 (0.6) 5 (0.7) 9 (0.6)DemographicsRSVpreF/influenza vaccine
coadministration
SIIV, seasonal inactivated influenza vaccine
WRDM  Worldwide Medical & Safety 15Geometric Mean Ratios with 95% CIs –Evaluable RSV Immunogenicity Population and
Evaluable SIIV Immunogenicity Population
.
GMRs and 2- sided confidence intervals (CIs) calculated by exponentiating the mean difference of the logarithms of the titers (coadministration minus sequential -administration) and corresponding
confidence intervals (CIs) (based on Student’s t distribution).
GMR, geometric mean ratio; GMT, geometric mean titer; HAI, hemagglutination inhibition assay; NT, neutralizing titer; RSV, respi ratory syncytial virusNon-inferiority Demonstrated
by SIIV HAI and RSV Neutralizing Titer GMRs
Comparison, by SIIV/RSV Subgroup GMR (95% CI)
SIIV: HAI: H1N1 A/Victoria 0.86 (0.769, 0.963)
SIIV: HAI: H3N2 A/Darwin 0.77 (0.680, 0.866)
SIIV: HAI: B/Austria 0.90 (0.789, 1.019)
SIIV: HAI: B/Phuket 0.87 (0.779, 0.964)
RSVpreF: NT: RSV A 0.86 (0.785, 0.951)
RSVpreF: NT: RSV B 0.85 (0.766, 0.943)
0.667 1.0 1.5
GMT RatioRSVpreF/influenza vaccine
coadministration
16 WRDM  Worldwide Medical & SafetySimilar HAI Titer Seroprotection and Seroconversion at 1 Month
in Coadministration and Sequential Administration Groups
Coadministration
(RSVpreF + SIIV)/PlaceboSequential Administration
(Placebo + SIIV)/RSVpreF
Serostatus, Strain % (95% CI) % (95% CI)
Seroprotection1
1 month after vaccination
H1N1 A/Victoria 91.6 (89.3, 93.6) 94.3 (92.3, 95.9)
H3N2 A/Darwin 87.9 (85.2, 90.3) 91.0 (88.6, 93.0)
B/Austria 85.3 (82.4, 87.9) 89.5 (87.0, 91.7)
B/Phuket 88.4 (85.7, 90.7) 92.6 (90.4, 94.4)
Seroconversion2
H1N1 A/Victoria 36.6 (32.9, 40.3) 43.9 (40.1, 47.7)
H3N2 A/Darwin 58.8 (55.0, 62.6) 62.6 (58.9, 66.3)
B/Austria 39.5 (35.8, 43.3) 47.3 (43.5, 51.1)
B/Phuket 25.3 (22.1, 28.8) 28.0 (24.6, 31.5)
1Seroprotection:  HAI titer ≥ 1:40
2Seroconversion: ≥ 4- fold rise from before to after receipt of SIIV if the HAI titer is ≥1:10 before SIIV or if the after SIIV HAI titer is ≥ 1:40 where the before SIIV is <1:10RSVpreF/influenza vaccine
coadministration
17 WRDM  Worldwide Medical & SafetyParticipants reporting local reactions by maximum severity within 7 days after each vaccination0102030405060708090100
Vaccine as Administered1.3%
10.1%0.7%
7.6%0.9%6.5%0.9%
11.5%0.9%2.1%0.1%0.6%0.1%0.3%0.9%0.7%0.9%2.1%0%
0.3%0%
0.1%0.1%0.6%1.2%Injection Site Pain Redness Swelling
% of Participants
Local r
eactions evaluated on the arm receiving RSVpreF/placebo; no assessment of local reactogenicity at SIIV injection site.
Local reactions after RSVpreF had median onset 2 to 3 days after vaccination and median duration of 1 to 2 days
Only 1 severe local reaction reported (swelling), in the sequential administration group at Visit 2Local Reactions Mostly Mild or ModerateRSVpreF/influenza vaccine
coadministration
SIIV, seasonal inactivated influenza vaccine
18 Confidential WRDM  Worldwide Medical & SafetySystemic Events Mostly Mild or Moderate
0.9%
13.7%
15.4%0.3%
11.3%15.6%
7.5%
10.1%0.6%7.0%
11.5%0.1%5.8%
13.7%0.6%6.1%
14.3%0.1%4.6%
10.4%0.1%5.4%
10.6%
0.6%0.4%0.1%0.4%0.1%0.3%0.1%1.0%0.4%2.7%4.4%0.3%1.2%4.6%1.0%3.7%1.2%4.2%2.0%6.1%0.1%1.2%4.9%1.5%3.2%0.3%1.5%4.5%0.1%5.6%
10.1% 4.8%7.5%2.1%6.9%0.1%3.5%5.8%0.4%4.3%6.8%3.5%5.8%2.2%5.1%0.1%2.8%4.2%0.4%0.3%1.1%0.3%0.3%0.9%0.1%0.7%0.1%1.0%
Fatigue Fever Headache Vomiting Nausea Diarrhea Muscle Pain Joint Pain
*Vaccine as Administered100
90
80s70pant60ci i t
50ar  P of
40 %
302010
0
RSVpreF/influenza vaccine
coadministration
Participants reporting systemic events by maximum severity within 7 days after each vaccination
Systemic events after RSVpreF+SIIV had median onset 2 to 4 days after vaccination and median duration of 1 to 2 days
SIIV, seasonal inactivated influenza vaccine
19 WRDM  Worldwide Medical & SafetyAdverse Events, by Category, within One Month
after Vaccination: Safety PopulationRSVpreF/influenza vaccine
coadministration
Adverse Event CategoryRSVpreF+SIIV
(N = 703)Placeb o+SIIV
(N = 695)Placeb o
(N = 689)RSVpreF
(N = 691)
n(%) n(%) n(%) n(%)
Any event 154 ( 21.9) 134 ( 19.3) 117 (17.0) 115 (16.6)
Related 9 (1.3) 3 (0.4) 3 (0.4) 5 (0.7)
Serious 8 (1.1) 6 (0.9) 2 (0.3) 5 (0.7)
Related 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)
Death 0 (0.0) 1 (0.1) 0 (0.0) 0 (0.0)
Immediate 3 (0.4) 1 (0.1) 1 (0.1) 0 (0.0)
Any reactogenicity reported as adverse events (from either reactogenicity subset or non- reactogenicity subset) during the specif ied time period are included in this table.
Immediate AE refers to an AE reported in the 30- minute post -vaccination observation period.
AE, adverse event; NDCMC, newly diagnosed chronic medical condition; SAE, serious adverse event; SIIV, seasonal inactivated i nfluenza vaccine.
20 Confidential WRDM Worldwide Medical & SafetyRSVpreF Older Adult Clinical Development Program Updates
–Conclusions
•Favorable overall safety profile of RSVpreF
•RSVpreF remained efficacious in prevention of
RSV-LRTD
•Through end of season 1
•In mid-season 2
•Average 13.9 months of follow up since vaccination•RSVpreF safe and well tolerated when
coadministered with influenza vaccine
•Non-inferior immune responses when RSVpreF coadministered with influenza
vaccineRENOIR Phase 3 Pivotal Efficacy
–Season 1 and Mid -Season 2RSVpreF Coadministration with
Influenza Vaccine
21 Confidential Breakthroughs that change patients’ livesThank you

Summary: Breakthroughs that change patients’ lives 1 ConfidentialAlejandra Gurtman, MD, FIDSA Presentation to ACIPJune 21, 2023RSVpreF Older Adults Clinical Development Program Updates 2 Confidential WRDM Worldwide Medical & SafetyABRYSVOTM(Respiratory Syncytial Virus Vaccine) FDA Approval on 5/31/2023RSVpreF Older Adult  –Clinical Development Program Updates Indication Active immunization for the prevention of lower respiratory tract disease (LRTD)  caused by respiratory syncytial virus (RSV) in…


03 RSV Adults Friedland 508

CO-1
GSK’s RSVPreF3 OA Vaccine (AREXVY)
AREXVY was approved by FDA on May 3, 2023, and is indicated for the prevention
of LRTD caused by RSV in adults 60 and older, as a single dose.
ACIP June 21, 2023
Leonard Friedland, MD
Vice President, Scientific Affairs and Public Health
Presentation by GSK at ACIP June 21, 2023

CO-2
Presentation Overview
Efficacy and safety results over 2 full RSV seasons from pivotal Phase 3 Study
▪1 dose of AREXVY provides durable efficacy against RSV -associated LRTD over 2 full
RSV seasons, including against severe RSV disease, in adults with underlying
comorbidities, and across advancing ages
▪2nddose 12 months after 1stdose does not appear to confer additional efficacy in
overall population
Immunogenicity and safety results from 2 co -administration trials with influenza
vaccines (adjuvanted, high dose)
▪AREXVY can be administered with all types of commonly used influenza vaccines
LRTD: lower respiratory tract disease Presentation by GSK at ACIP June 21, 2023

CO-3
Pivotal Efficacy and Safety Study ( AReSVi -006):
Results Through 2 Full RSV Seasons
Phase 3, randomized, placebo -controlled, multi -country study to
demonstrate efficacy and safety of single and annual revaccination
doses in adults 60 years and older
Presentation by GSK at ACIP June 21, 2023
CO-4
Ongoing AReSVi -006 Phase 3 Trial Design
Randomized, placebo -controlled, observer -blind, multi -country efficacy study
Adults
≥ 60 years
N = 24,966
AREXVY
(annual group, dose 2)
Placebo
(AREXVY single dose)R
AREXVY
N = 12,4 67
Placebo
N = 12,499Season 1
2021 –2022Season 2
2022 –2023Season 3
2023 –2024
R
AREXVY
(annual group, dose 3)
Placebo
(AREXVY single dose)
Study Initiated May 2021
(Northern hemisphere)End of S2 Analysis
Mar 2023
End of S1 Analysis
Apr 2022
Placebo
Placebo
*RT-PCR confirmed; †LRTD defined as ≥ 2 lower respiratory symptoms/signs for ≥ 24 hours including ≥1 lower respiratory sign OR ≥ 3 lower
respiratory symptoms for ≥ 24 hours; RT -PCR: reverse transcriptase polymerase chain reactionConfirmatory secondary endpoint: Evaluate efficacy of AREXVY in prevention of RSV* -LRTD†in adults ≥ 60 YOA
over 2 seasons, following a single dose of AREXVY and following annual revaccination dose
▪All RSV -LRTD cases adjudicated by independent external adjudication committee
▪Success criterion: lower limit of 2 -sided 97.5% CI for vaccine efficacy > 20%Mid-S2 Analysis Nov
2022AReSVi -006
Presentation by GSK at ACIP June 21, 2023
CO-5
AReSVi -006 Case Definitions
ARI
≥ 2 respiratory
symptoms or signs
OR
≥ 1 respiratory
and 1 systemic
symptom or sign for
at least 24 hours Respiratory symptoms or signs
▪Fever/feverishness
▪Fatigue
▪Body aches
▪Headache
▪Decreased appetiteUpper respiratory
symptoms or signsLower respiratory
symptomsLower respiratory
signsSystemic
symptoms or signs
▪Sputum
▪Cough
▪Dyspnea▪Wheezing
▪Crackles/rhonchi
▪Tachypnea
▪Hypoxemia
▪O2 supplement▪Nasal congestion
▪Sore throat
LRTD*
≥ 2 lower respiratory symptoms
or signs
(≥ 1 sign)
OR
≥ 3 lower respiratory symptoms
for at least 24 hours ▪Sputum
▪Cough
▪DyspneaLower respiratory
symptomsLower respiratory
signs
▪Wheezing
▪Crackles/rhonchi
▪Tachypnea
▪Hypoxemia
▪O2 supplement
Severe LRTD*
≥ 2 lower respiratory signs
OR
episode preventing normal,
everyday activitiesLower respiratory
signs
▪Wheezing
▪Crackles/rhonchi
▪Tachypnea
▪Hypoxemia
▪O2 supplementAReSVi -006
Presentation by GSK at ACIP June 21, 2023 *USPI case definitions
CO-6
AREXVY Produces Durable Vaccine Efficacy Against RSV -LRTD
Over 2 Full SeasonsAReSVi -006
Median
Follow -Up
(months)AREXVY Placebo
VE
(95% CI)VE
(95% CI) Number of events
Single DoseW/o season
as covariate#W/ season
as covariate¶
Season 1*
VE 16.7 7 / 12,466 40 / 12,49482.6%
(57.9, 94.1)82.6%
(57.9, 94.1)
Mid Season 2
Post dose 114 15 / 12,469 85 / 12,49880.9%#
(66.7, 89.8)77.3%¶
(60.2, 87.9)
Season 2 Only
Post dose 26.4 20 / 4,991 91 / 10,03156.1%
(28.2, 74.4)56.1%
(28.2, 74.4)
Season 1 + 2** 18 30 / 12,469 139 / 12,49874.5%#
(60.0, 84.5)67.2%¶
(48.2, 80.0)
Annual (2 doses, ~12 months apart)
Season 2 Only
Post dose 26.4 20 / 4,966 91 / 10,03155.9%
(27.9, 74.3)55.9%
(27.9, 74.3)
Seasons 1 + 2** 18 30 / 12,469 139 / 12,49874.5%#
(60.0, 84.4)67.1%¶
(48.1, 80.0)
0 20 40 60 80 100Modified exposed set
*96.95% CI for VE 1 ;**97.5% CI for Season 1 + 2 Presentation by GSK at ACIP June 21, 2023
CO-7
AREXVY Produces Durable Vaccine Efficacy Against
RSV-Severe LRTD Over 2 Full SeasonsAReSVi -006
Presentation by GSK at ACIP June 21, 2023Modified exposed set
*96.95% CI for VE 1 ;**97.5% CI for Season 1 + 2Median
Follow -Up
(months)AREXVY Placebo
VE
(95% CI)VE
(95% CI) Number of events
Single DoseW/o season
as covariate#W/ season
as covariate¶
Season 1*
VE 16.7 1 / 12,466 17 / 12,49494.1%
(62.4, 99.9)94.1%
(62.4, 99.9)
Mid Season 2
Post dose 114 4 / 12,469 33 / 12,49886.8%#
(63.0, 96.6)84.6%¶
(56.4, 96.1)
Season 2 Only
Post dose 26.4 5 / 4,991 28 / 10,03164.2%
(6.2, 89.2)64.2%
(6.2, 89.2)
Season 1 + 2** 18 7 / 12,469 48 / 12,49882.7%#
(61.6, 93.4)78.8%¶
(52.6, 92.0)
Annual (2 doses, ~12 months apart)
Season 2 Only
Post dose 26.4 5 / 4,966 28 / 10,03164.1%
(5.9, 89.2)64.1%
(5.9, 89.2)
Seasons 1 + 2** 18 7/12,469 48/ 12,49882.7%#
(61.6, 93.4)78.8%¶
(52.5, 92.0)
0 20 40 60 80 100
CO-8
AREXVY Produces Durable Vaccine Efficacy Against RSV -LRTD in
Vulnerable Populations Over 2 Full Seasons
Vaccine efficacy in frail participants cannot be concluded due to low number of cases accrued  AREXVY PlaceboVE
(95% CI)VE
(95% CI) Number of events
Season 1*
(Median follow -up = 6.7 months)
≥ 1 pre -existing
comorbidity of interest1 / 4,937 18 / 4,86194.6%
(65.9, 99.9)94.6%
(65.9, 99.9)
Pre-frail 1 / 4,792 14 / 4,77892.9%
(53.4, 99.8)92.9%
(53.4, 99.8)
Single dose over 2 seasons†
(Median follow -up = 18 months)W/o season
as covariate#W/ season
as covariate¶
≥ 1 pre -existing
comorbidity of interest16 / 4,983 72 / 4,91974.5%#
(55.7, 86.1)66.7%¶
(41.8, 82.0)
Pre-frail 8 / 4,794 47 / 4,77980.0%#
(57.3, 91.8)73.3%¶
(42.4, 89.2)
0 20 40 60 80 100
Comorbidities of interest include chronic obstructive pulmonary disease, asthma, any chronic respiratory or pulmonary disease, and chronic heart failure
(cardiorespiratory condition) and diabetes mellitus type 1 or type 2 and advanced liver or renal disease (endocrine or metabo liccondition
*April 2022 analysis; †From 15 days post Dose 1 up to end of Season 2 in Northern HemisphereAReSVi -006
Presentation by GSK at ACIP June 21, 2023
CO-9
AREXVY PlaceboVE
(95% CI)VE
(95% CI) Number of events
Season 1*
(Median follow -up = 6.7 months)
≥ 60 YOA*** 7 / 12,466 40 / 12,49482.6%
(57.9, 94.1)82.6%
(57.9, 94.1)
60 –69 YOA 4 / 6,963 21 / 6,97981.0%
(43.6, 95.3)81.0%
(43.6, 95.3)
70 –79 YOA 1 / 4,487 16 / 4,48793.8%
(60.2, 99.9)93.8%
(60.2, 99.9)
Single dose over 2 seasons†
(Median follow -up = 18 months)W/o season
as covariate#W/ season
as covariate¶
≥ 60 YOA**** 30 / 12,469 139/ 12,49874.5%#
(60.0, 84.5) 67.2%¶
(48.2, 80.0)
60 –69 YOA 17/ 6,963 74/ 6,98172.9%#
(53.7, 85.0)65.4%¶
(40.4, 80.9)
70 –79 YOA 9 / 4,489 55/ 4,48980.7%#
(60.6, 91.6)74.9%¶
(48.4, 89.2)AREXVY Produces Durable Vaccine Efficacy Against RSV LRTD
Across Advancing Ages Over 2 Full Seasons
Vaccine efficacy in adults ≥ 80 years of age cannot be concluded due to low number of cases accrued  0 20 40 60 80 100
*April 2022 analysis; ***96.95% CI; ****97.5% CI; YOA: years of age;
†From 15 days post Dose 1 up to end of Season 2 in Northern HemisphereAReSVi -006
Presentation by GSK at ACIP June 21, 2023
CO-10
AREXVY Produces Durable Vaccine Efficacy Against RSV -A LRTD
and RSV -B LRTD Over 2 Full Seasons
*April 2022 analysis; †From 15 days post Dose 1 up to end of Season 2 in Northern HemisphereAReSVi -006
Presentation by GSK at ACIP June 21, 2023AREXVY PlaceboVE
(95% CI)VE
(95% CI) Number of events
Season 1*
(Median follow -up = 6.7 months)
RSV-A 2/ 12,466 13/ 12,49484.6%
(32.1, 98.3)84.6%
(32.1, 98.3)
RSV-B 5/ 12,466 26/ 12,49480.9%
(49.4, 94.3)80.9%
(49.4, 94.3)
Single dose over 2 seasons†
(Median follow -up = 18 months)W/o season
as covariate#W/ season
as covariate¶
RSV-A 6/ 12,469 48/ 12,49885.2%#
(65.4, 94.8)80.5%¶
(54.0, 93.2)
RSV-B 24/ 12,469 90/ 12,49868.5%#
(50.2, 80.8)59.7%¶
(35.8, 75.5)
0 20 40 60 80 100
CO-11
Reactogenicity Profile of 2ndDose in Line with 1stDose
Solicited AEs Reported Within 4 Days of Vaccination (Solicited Safety Set)
AREXVY Season 1 n=879; Placebo Season 1 n=878; 2 doses Season 2 n=326 (received AREXVY in Season 1 and Season 2);
1 dose Season 2 n=345 (received AREXVY in Season 1 and Placebo  in Season 2);
Placebo Season 2 n=666 (received Placebo in Season 1 and Season 2)AReSVi -006: Season 2
Presentation by GSK at ACIP June 21, 2023Local Systemic8.1
1.19.8
0.9 0.160.9
9.352.1
9.0 7.66.0
0.87.1
0.3 0.318.0
6.416.9
5.8 7.233.7
16.130.1
12.8 12.0
2.00.31.80.3 0.627.2
12.622.1
12.29.029.0
8.225.2
5.87.8
020406080100
RSVPreF3 OA
Placebo
Annual
1 dose
Placebo
RSVPreF3 OA
Placebo
Annual
1 dose
Placebo
RSVPreF3 OA
Placebo
Annual
1 dose
Placebo
RSVPreF3 OA
Placebo
Annual
1 dose
Placebo
RSVPreF3 OA
Placebo
Annual
1 dose
Placebo
RSVPreF3 OA
Placebo
Annual
1 dose
Placebo
RSVPreF3 OA
Placebo
Annual
1 dose
Placebo
RSVPreF3 OA
Placebo
Annual
1 dose
Placebo
Erythema Pain Swelling Arthralgia Fatigue Fever Headache MyalgiaAREXVY
AREXVY
AREXVY
AREXVY
AREXVY
AREXVY
AREXVY
AREXVY2 doses AREXVY
(1st& 2ndseason)1 dose AREXVY (1stseason)
/ Placebo (2ndseason)Placebo
(1st& 2nd season)1 dose AREXVY
(1stseason)Season 22 doses
2 doses
2 doses
2 doses
2 doses
2 doses
2 doses
2 doses% of
Participants
CO-12
Safety Profile of 2ndDose in Line with 1stDose
Unsolicited AEs, SAEs, fatal SAEs, and pIMDs
AREXVY Season 1 n=12,467; Placebo Season 1 n=12,499; 2 doses Season 2 n=4,966 (received AREXVY in Season 1 and Season 2); 1 d oseSeason 2 n=4,991
(received AREXVY in Season 1 and Placebo in Season 2); Placebo Season 2 n=10,033 (received Placebo in Season 1 and Season 2)
DLP: data lock point; pIMD :potential immune -mediated diseaseAReSVi -006
Presentation by GSK at ACIP June 21, 2023Unsolicited AEs
Within 30 daysSAEs
Up to 6 months post
vaccinationUp to DLP (Season 2)pIMDs Fatal SAEs33.0
17.828.5
15.8 14.9
4.2 4.0 4.2 4.4 4.6
0.4 0.5 0.4 0.5 0.4 0.3 0.3 0.3 0.4 0.3
020406080100
AREXVY
Placebo
2 doses
1 dose
Placebo
AREXVY
Placebo
2 doses
1 dose
Placebo
AREXVY
Placebo
2 doses
1 dose
Placebo
AREXVY
Placebo
2 doses
1 dose
Placebo% of
Participants
2.0 1.3 2.2 1.1 1.2Grade 32 doses AREXVY
(1st& 2ndseason)1 dose AREXVY (1stseason)
/ Placebo (2ndseason)Placebo
(1st& 2nd season)1 dose AREXVY
(1stseason)Season 2
CO-13
Influenza Vaccine Co -administration Studies:
Immunogenicity and Safety
Open -label, randomized, controlled, multi -country studies to evaluate immune
response, safety, and reactogenicity of AREXVY when co -administered with
influenza vaccines in adults aged 60 years and above (RSV OA=ADJ -007) or
65 years and above (RSV OA=ADJ -008 and RSV OA=ADJ -017)
Presentation by GSK at ACIP June 21, 2023
CO-14
Phase 3 Influenza Vaccine Co -Administration Studies: Designs1−3
Open -label, randomized controlled studies evaluating immunogenicity, safety, and
reactogenicity of AREXVY co -administered with:
▪FLU-QIV (RSV OA=ADJ -007; Southern hemisphere)1
▪FLU-QIV-HD (RSV OA=ADJ -008; Northern hemisphere)2
▪FLU-aQIV (RSV OA=ADJ -017; Europe)3
Co-Ad group: Participants receiving single dose of RSVPreF3 OA investigational vaccine and single dose of FLU vaccine at Visit 1 . Control group: Participants
receiving a single dose of FLU vaccine at Visit 1 (Day 1), followed by a single dose of the RSVPreF3 OA investigational vacci ne at Visit 2. FLU-aQIV : adjuvanted
quadrivalent influenza vaccine; FLU -QIV: quadrivalent influenza vaccine; FLU -QIV-HD: quadrivalent influenza vaccine -high dose. 1. ClinicalTrials.gov, 2022.
NCT04841577. https://clinicaltrials.gov/ct2/show/NCT04841577 ; 2. ClinicalTrials.gov, 2023. NCT05559476. https://clinicaltrials.gov/ct2/show/NCT05559476 ;
3. ClinicalTrials.gov, 2023. NCT05568797. https://clinicaltrials.gov/ct2/show/NCT05568797 .  Accessed May 2023
Co-administration
(AREXVY + FLU)
Older Adults
FLU-QIV: ≥ 60 YOA
N = 8681
FLU-QIV-HD: ≥ 65 YOA
N = 1,0082
FLU-aQIV: ≥ 65 YOA
N = 1,0263
Control
(FLU)
Visit 1
(Day 1)Visit 2
(Day 31)Day 61R
Control
(AREXVY)
Co-Ad
Control
Co-Ad
Safety Monitoring
through 6 monthsBlood sampling
AREXVY
FLU
Presentation by GSK at ACIP June 21, 2023

CO-15
Co-Administration of AREXVY and Licensed FLU -QIV-HD
*RSV -A preliminary, final results pending
Flu response evaluated using HI and RSV response evaluated using NAb (ED 60); HI: Hemagglutination RSV OA=ADJ -008: FLU QIV -HD
AntibodyCo-Ad
NControl
NGMT Ratio (Control Over Co -Administration)
1 Month After Vaccination
Per Protocol SetGMT Ratio
(95% CI)
Flu A/Darwin H3N2 458 4410.98
(0.84, 1.14)
Flu A/Victoria H1N1 452 4350.93
(0.80, 1.08)
Flu B/Austria/Victoria 458 4410.95
(0.88, 1.03)
Flu B/Phuket/Yamagata 456 4410.92
(0.84, 1.02)
RSV-A* 459 3581.18
(1.04, 1.35)
RSV-B 459 3571.02
(0.89, 1.16)
0.5 1 1.5
Presentation by GSK at ACIP June 21, 2023Success Criteria: Upper limit ≤ 1.5 of 2 -sided 95% CI for Group GMT Ratio (Control Group divided by Co -Ad Group)
for RSV vaccine and for each of FLU vaccine strains
CO-16
Co-Administration of AREXVY and Licensed Flu -Adjuvanted QIV
*Lower HI titers observed than expected, investigation ongoing; **RSV -A preliminary, final results pending
Flu response evaluated using HI and RSV response evaluated using NAb (ED 60); HI: Hemagglutination RSV OA=ADJ -017: FLU aQIV
Presentation by GSK at ACIP June 21, 2023Success Criteria: Upper limit ≤ 1.5 of 2 -sided 95% CI for Group GMT Ratio (Control Group divided by Co -Ad Group)
for RSV vaccine and for each of FLU vaccine strainsAntibodyCo-Ad
NControl
NGMT Ratio (Control Over Co -Administration)
1 Month After Vaccination
Per Protocol SetGMT Ratio
(95% CI)
Flu A/Darwin H3N2* 433 4021.31
(1.13, 1.52)
Flu A/Victoria H1N1 424 3981.03
(0.91, 1.18)
Flu B/Austria/Victoria 433 4020.97
(0.89, 1.05)
Flu B/Phuket/Yamagata 432 4021.04
(0.95, 1.12)
RSV-A** 475 3770.98
(0.87, 1.11)
RSV-B 473 3771.16
(1.03, 1.31)
0.5 1 1.5 2
CO-17
Modified Set: Solicited Local AEs Within 4 Days Post Vaccination
Grade 3: > 100 mm for erythema and swelling; Grade 3 pain: significant pain at rest; prevents normal everyday activities. Fever: temperature ≥ 38.0 C/100.4 F
by any route (oral, axillary or tympanic); Grade 3 fever: > 39.0 C/102.2 F.
Grade 3 headache, fatigue, myalgia, arthralgia: preventing normal activity4.0% 4.6%47.0%
42.5%
4.5% 5.6%
0% 0%1.2% 0.5%
0% 0.2%
020406080100
Co-Ad
Visit 1FLU
Visit 1Co-Ad
Visit 1FLU
Visit 1Co-Ad
Visit 1FLU
Visit 1FLU-QIV-HD
Erythema SwellingPain
4.3% 4.3%55.6%
46.3%
4.0% 4.3%
0.2% 0.3%2.1%0.3%0% 0.3%020406080100
Co-Ad
Visit 1AREXVY
Visit 2Co-Ad
Visit 1AREXVY
Visit 2Co-Ad
Visit 1AREXVY
Visit 2AREXVY
Erythema Swelling
% of
ParticipantsPainRSV OA=ADJ -008: FLU QIV -HD
Presentation by GSK at ACIP June 21, 2023Co-Ad Grade 3 FLU AREXVY
CO-18
Exposed Set: Solicited Local AEs Within 7 Days Post Vaccination
4.5% 3.7%51.7%
44.8%
3.9% 4.3%
0% 0%0.2% 0%0% 0%020406080100
Co-Ad
Visit 1FLU
Visit 1Co-Ad
Visit 1FLU
Visit 1Co-Ad
Visit 1FLU
Visit 1FLU-aQIV
Erythema Swelling Pain
11.8%9.5%65.9%
58.8%
8.7%6.0%
1.9% 1.3%0.6% 0.2%1.0% 0.7%020406080100
Co-Ad
Visit 1AREXVY
Visit 2Co-Ad
Visit 1AREXVY
Visit 2Co-Ad
Visit 1AREXVY
Visit 2AREXVY
Erythema Swelling
% of
ParticipantsPainRSV OA=ADJ -017: FLU aQIV
Grade 3: > 100 mm for erythema and swelling; Grade 3 pain: significant pain at rest; prevents normal everyday activities. Fever: temperature ≥ 38.0 C/100.4 F
by any route (oral, axillary or tympanic); Grade 3 fever: > 39.0 C/102.2 F.
Grade 3 headache, fatigue, myalgia, arthralgia: preventing normal activity Presentation by GSK at ACIP June 21, 2023Co-Ad Grade 3 FLU AREXVY
CO-19
Modified Set: Solicited Systemic AEs Within 4 Days
Post Vaccination
Grade 3: >100 mm for erythema and swelling. Grade 3 pain: significant pain at rest; prevents normal everyday activities.
Fever: temperature ≥ 38.0 °C/100.4°F by any route (oral, axillary or tympanic); Grade 3 fever: > 39.0 °C/102.2°F.
Grade 3 headache, fatigue, myalgia, arthralgia: preventing normal activityRSV OA=ADJ -008: FLU QIV -HD
Presentation by GSK at ACIP June 21, 202316.1%13.8%13.0%30.5%
22.0% 23.5%
2.1% 0.7% 2.0%24.3%
17.1% 19.0%40.2%
34.1%
31.3%
0.7% 0.7% 0.3% 0.9% 1.2% 0.5%0.2% 0.2% 0.5%1.9%0% 0.3%1.4% 1.4%0.3%
020406080100
Co-Ad
Visit 1FLU
Visit 1AREXVY
Visit 2Co-Ad
Visit 1FLU
Visit 1AREXVY
Visit 2Co-Ad
Visit 1FLU
Visit 1AREXVY
Visit 2Co-Ad
Visit 1FLU
Visit 1AREXVY
Visit 2Co-Ad
Visit 1FLU
Visit 1AREXVY
Visit 2Arthralgia Fatigue Fever Headache MyalgiaSolicited Systemic Adverse Events
% of
ParticipantsCo-Ad Grade 3 FLU AREXVY
CO-20
Exposed Set: Solicited Systemic AEs Within 7 Days
Post Vaccination
Grade 3: >100 mm for erythema and swelling. Grade 3 pain: significant pain at rest; prevents normal everyday activities.
Fever: temperature ≥ 38.0 °C/100.4°F by any route (oral, axillary or tympanic); Grade 3 fever: > 39.0 °C/102.2°F.
Grade 3 headache, fatigue, myalgia, arthralgia: preventing normal activityRSV OA=ADJ -017: FLU aQIV
Presentation by GSK at ACIP June 21, 202325.8%
15.6% 17.1%45.7%
28.7%29.9%
2.1% 0.6% 1.1%32.2%
19.5%23.7%39.0%
23.0%31.9%
0% 0% 0.2%0.2% 0.2% 0.2%0.2% 0% 0.2% 0% 0.2% 0% 0% 0.2% 0%
020406080100
Co-Ad
Visit 1FLU
Visit 1AREXVY
Visit 2Co-Ad
Visit 1FLU
Visit 1AREXVY
Visit 2Co-Ad
Visit 1FLU
Visit 1AREXVY
Visit 2Co-Ad
Visit 1FLU
Visit 1AREXVY
Visit 2Co-Ad
Visit 1FLU
Visit 1AREXVY
Visit 2% of
ParticipantsArthralgia Fatigue Fever Headache MyalgiaSolicited Systemic Adverse EventsCo-Ad Grade 3 FLU AREXVY
CO-21
Summary of Findings
1 dose of AREXVY provides durable efficacy against RSV -associated LRTD for 2 full RSV
seasons, including against severe RSV disease, in adults with underlying comorbidities, and
across advancing ages
Revaccination after 12 months does not appear to confer additional efficacy benefit for overall
population; future data will inform optimal timing of revaccination
Reactogenicity and safety profiles of 2nddose in line with 1stdose; important for future
revaccination consideration
Across all studies no new cases of GBS, ADEM, or other neuroinflammatory demyelinating
disorders with additional exposure
Presentation by GSK at ACIP June 21, 2023
AREXVY can be administered with all types of commonly used influenza vaccines

QA-22
AReSVi -004 Phase 3 Trial Design1
*Primary endpoints: NAb geometric mean titers (RSV -A and RSV -B) at Day 1 (pre -vaccination), D31, M6, and M12 post -dose 1; †CMI response in terms of frequency of
RSVPreF3 -specific CD4+ and/or CD8+ T -cells expressing at least 2 activation markers. CD: cluster of differentiation; CMI: cell -mediated immune
1. ClinicalTrials.gov. 2021. NCT04732871. https://clinicaltrials.gov/ct2/show/NCT04732871 (accessed May 2023)AReSVi -004
AREXVY: 1 initial dose, annual revaccination
Older adults
≥ 60 years
N=1653
Randomized
3:1:1
AREXVY: 1 initial dose, revaccination M24
AREXVY: 1 dose, no revaccination
Day 1
 Month 12 Month 24
Primary objective: Evaluate humoral immune response following 1 -dose primary schedule up to 12 months post -dose 1*
Key secondary objectives: Evaluate humoral and CMI† responses following 1 -dose primary schedule and revaccination
doses, up to study end (Month 36)
Safety monitoring: Throughout studyR
Study initiated Feb 2021
QA-23
Immunogenicity Overview Through Month 18 Post Vaccination
RSV-B Serum Neutralization Titers
 RSV-A Serum Neutralization Titers
 RSVPreF3 -specific CD4+ T -cells
Timepoint (days)
RSVPreF 3 CD4+ T -cells, /106cells (GM) GMT (ED60)
GMT (ED60)
Timepoint (days) Timepoint (days)020004000600080001000012000
0 200 400 600**~10X
**~3X~6X
020004000600080001000012000
0 200 400 600**~8.X
**~2.4X**~4X
05001000150020002500
0 200 400 6001 dose 2 doses 1 dose 2 doses 1 dose 2 doses
M6 M12 M18 D0 M6 M12 M18 D0 M6 M12 M18 D0**”~2 -4X* **2-3X
**versus before vaccination 1; CD4+ T -cells expressing ≥2 activation markers including ≥1 cytokine among CD40L, 4 -1BB, IL -2, TNF -α, IFN-γ, IL-13, IL -17 (events/106
cells; by intracellular staining). ED: Estimated Dilution; ED60: serum dilution inducing 60% inhibition in plaque -forming units; GMT: geometric mean titer; IL:
interleukin; TNF: tumor necrosis factorAReSVi -004
*RSV -A preliminary, final results pending

Summary: CO-1 GSK’s RSVPreF3 OA Vaccine (AREXVY) AREXVY was approved by FDA on May 3, 2023, and is indicated for the prevention  of LRTD caused by RSV in adults 60 and older, as a single dose. ACIP June 21, 2023 Leonard Friedland, MD Vice President, Scientific Affairs and Public Health   Presentation by GSK at ACIP June 21, 2023  CO-2 Presentation Overview Efficacy and safety results over 2 full RSV seasons from pivotal Phase 3 Study ▪1 dose of AREXVY provides durable efficacy against RSV -associated…


04 RSV Adults Hutton 508

Economic Analysis of RSV
Vaccination in Older Adults
David W. Hutton, PhD, MS
Associate Professor, Health Management and Policy, School of Public Health
Associate Professor of Global Public Health, School of Public Health
Associate Professor, Industrial and Operations Engineering, College of Engineering
University of Michigan

Research Team
University of Michigan
•David Hutton, PhD
•Lisa Prosser, PhD
•Angela Rose, MPH
•Kerra Mercon , MSCDC
•Michael Melgar , MD
•Mila Prill, MSPH
•Jamison Pike, PhD
•Ismael Ortega -Sanchez, PhD
•Fiona Havers, MD
•Michael Whitaker, MPH
•Christopher Taylor, PhD
•Amadea Britton, MD
2
Conflicts of interest statements
–No known conflict of interests.
3
Methods: Study question
•Determine the cost -effectiveness of RSV vaccination by:
•Evaluating the population burden of disease in the US
population
•Comparing vaccination to no vaccination using the incremental
cost-effectiveness ratio
•Scenario analyses exploring uncertainty.
•Perspective: Societal
•Major updates:
•Update to base case incidence of RSV
•Incorporation of season 2 efficacy of a single vaccine dose
•Alignment of vaccine price with that assumed by manufacturers
4
Methods: Intervention(s)
•Target population: US adults, stratified by age
•Interventions: Pfizer and GSK vaccines
•Each compared to No Vaccination
•Base case assumes the age -based RSV vaccination
recommendation is for ages ≥65
•Timeframe: 2 years
•Analytic horizon: lifetime
•Discounting rate: 3%
5
Methods: Decision Tree Model
No
Vaccination
VaccinationInfection Hospitalization
ED
None of the aboveOutpatientAlive
DeadInfection
Adverse
EventsSystemic Reaction
Injection Site Reaction
None of the aboveSerious Adverse EventInfection Infection
6
Methods: Epidemiology
•Incidence of RSV
–Raw reported incidence may be underreported
because of imperfect PCR sensitivity
▪Base case assumption: 1.5x multiplier was applied to
crude incidence estimates
▪Lower bound: lower multiplier assuming 95% PCR
sensitivity (fewer missed cases)
▪Higher bound: upper bound from base case assumption
7For incidence of inpatient (RSV -NET), outpatient, and ED visits (McLaughlin et al. 2022), this applies the McLaughlin et al. mul tiplier of 1.5x to the crude
incidence estimates.
•McLaughlin JM, et al. Rates of Medically Attended RSV Among US Adults: A Systematic Review and Meta -analysis. Open Forum Infect Dis. 2022 Jun 17;9(7):ofac300. doi:
10.1093/ ofid/ofac300. PMID: 35873302; PMCID: PMC9301578.
Other studies speak directly to under -detection of RSV infection through use of upper respiratory PCR alone:
•Onwuchekwa C, Moreo LM, Menon S, Machado B, Curcio D, Kalina W, Atwell JE, Gessner BD, Siapka M, Agarwal N, Rubbrecht M. Under -ascertainment of Respiratory Syncytial
Virus infection in adults due to diagnostic testing limitations: A systematic literature review and meta -analysis. The Journal o f Infectious Diseases. 2023 Jan 20.
•Ramirez J, Carrico R, Wilde A, Junkins A, Furmanek S, Chandler T, Schulz P, Hubler R, Peyrani P, Liu Q, Trivedi S. Diagnosis of Respiratory Syncytial Virus in Adults Substantially
Increases When Adding Sputum, Saliva, and Serology Testing to Nasopharyngeal Swab RT –PCR. Infectious Diseases and Therapy. 2023 May 6:1 -1.
Methods: Epidemiology
Hospitalization
Variable Value Range Source
age 60 to <65 years 65.5 47.2 –101.3
CDC RSV -NETage 65 to <70 years 93.8 65.9 –149.1
age 70 to <75 years 118.7 85.5 –183.1
age ≥75 years 302.9 212.6 –489
•CDC RSV -NET data from RSV seasons: 2016 -17, 2017 -18, 2018 -19, and 2019 -2020.
•Base value is based upon the average burden adjusted rate over those four seasons where
“burden adjusted” means it is adjusted for 1.5x based on a reduced PCR test sensitivity *
•Range lower bound is based upon the average burden adjusted rate over those four seasons,
but it uses a different “burden adjustment” multiplier of a "Standard" PCR test sensitivity of
95%**.
•Range upper bound is based on the upper 95% confidence limit for the base estimates
* Kujawski SA, Whitaker M, Ritchey MD, Reingold AL, Chai SJ, Anderson EJ, Openo KP , Monroe M, Ryan P , Bye E, Como -Sabetti K, Bar ney GR, Muse A, Bennett NM, Felsen
CB, Thomas A, Crawford C, Talbot HK, Schaffner W, Gerber SI, Langley GE, Kim L. Rates of respiratory syncytial virus (RSV) -assoc iated hospitalization among adults with
congestive heart failure -United States, 2015 -2017. PLoS One. 2022 Mar 9;17(3):e0264890. doi: 10.1371/journal.pone.0264890. PMID: 35263382; PMCID: PMC8906631.
** McLaughlin JM, et al. Rates of Medically Attended RSV Among US Adults: A Systematic Review and Meta -analysis. Open Forum Infe ct Dis. 2022 Jun 17;9(7):ofac300.
doi: 10.1093/ ofid/ofac300. PMID: 35873302; PMCID: PMC9301578.8RSV incidence, per 100,000, Hospitalization
Methods: Epidemiology
ED and Outpatient
Variable Value Range Source
RSV incidence, per 100,000
Emergency Department
age 60 to <65 years 110.4 74 –132
McLaughlin 2022 age 65 to <74 years 200 133 –478
age ≥75 years 200 133 –478
RSV Incidence, per 100,000
Outpatient
age 60 to <65 years 1722 1148 –2041
McLaughlin 2022 age 65 to <74 years 2278 1519 –2893
age ≥75 years 2278 1519 –2893
9•McLaughlin et. al. is a Pfizer -sponsored meta -analysis
McLaughlin JM, Khan F, Begier E, Swerdlow DL, Jodar L, Falsey AR. Rates of Medically Attended RSV Among US Adults: A
Systematic Review and Meta -analysis. Open forum infectious diseases 2022 Jul (Vol. 9, No. 7, p. ofac300).
Methods: Incidence
Seasonality
Source: NREVSS (2015 -19)0%5%10%15%20%25%30%
Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug SepFraction of Annual Infections
10
0%10%20%30%40%50%60%70%80%90%100%
0 2 4 6 810 12 14 16 18 20 22 24 26 28 30 32 34 36Efficacy
Month
Against medically-attended RSV- LRTI/LRTD (hospitalization and ED)
Est. Against medically-attended RSV- LRTI/LRTD (hospitalization and ED)
Against medically-attended RSV-associated ARI (outpatient)
Est. Against medically-attended RSV-associated ARI (outpatient)
11Efficacy of a single vaccine dose
over time: Pfizer
Linear decay to
0% by 24 months84.6%
65.2%75.0%
55.0%
0%10%20%30%40%50%60%70%80%90%100%
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36Efficacy
Month
Against medically-attended RSV- LRTI/LRTD (hospitalization and ED)
Est. Against medically-attended RSV- LRTI/LRTD (hospitalization and ED)
Against medically-attended RSV-associated ARI (outpatient)
Est. Against medically-attended RSV-associated ARI (outpatient)87.5%
52.9%79.0%
27.8%Linear decay to
0% by 24 months
12Efficacy of a single vaccine dose
over time: GSK
Upper and Lower Bound Efficacy
Duration Scenarios
13GSK Pfizer
0%20%40%60%80%100%
0 20 40Efficacy
MonthAgainst medically-attended
RSV- LRTI/LRTD
(hospitalization and ED)
Base Shorter Longer0%20%40%60%80%100%
0 20 40Efficacy
MonthAgainst medically-attended
RSV- LRTI/LRTD
(hospitalization and ED)
Base Shorter Longer
Methods: RSV Medical Costs
Variable Value Range Source
Disease -specific
hospitalization costs (per
hospitalization)
age 60 to <65 years $21,417 9,288 –45,454
Ackerson 2020* age 65 to <75 years $21,417 10,491 –43,619
age ≥75 years $22,425 10,491 –43,619
Disease -specific ED costs
(per ED visit)
age 60 to <65 years $1,210 -
2016 Marketscan* age 65 to <75 years $1,210 -
age ≥75 years $1,210 -
Disease -specific
outpatient costs (per
outpatient visit)
age 60 to <65 years $117.58 65.88 -145.38 MarketScan
and Medicare FFS, 2020 -
2021age 65 to <75 years $100.86 50.48 -120.08
age ≥75 years $100.86 50.48 -120.08
*Updated to Q3 2022$ using GDP Deflator14
Methods: Additional Inputs
•Also included
–RSV mortality
–RSV QALYs lost
–RSV illness productivity costs
–Vaccination healthcare and productivity costs
–Vaccination adverse events
•Systemic reactions
•Injection site reactions
•Serious adverse events
•Medical costs
•Productivity costs
•These assumption remain unchanged from
February
15
Methods: Sensitivity analyses
•Sensitivity analyses conducted
–One-Way and Two -Way
–Age-based recommendation for RSV vaccination
•age ≥65 years
•age 60 to <65 years
–Vaccine cost
▪$180 -$340
•Scenario analysis: shorter and longer duration of
efficacy
16
Results: Base Case
•Cohort of US adult population age 65+ as
of 2020 Census
•Vaccine Cost:
–Pfizer: $200
–GSK: $270
•Two Year Timeframe
17
Number Needed to Vaccinate,
Pfizer
18
Two Year Timeframe
52
617
1,040
5,201
26,671
173
1,734 40
340
401
2,007
7,842
67
669
 - 5,000 10,000 15,000 20,000 25,000 30,000Number Needed to Vaccinate
 Age 60-64 age ≥65 years
Net Cost per Outcome Averted,
Pfizer
19Two Year Timeframe
Age-based vaccination recommendation: ≥65 years
Pfizer vaccine cost: $200Outpatient ED Hospitalizations ICU Stays Deaths
≥65 years $5,600 $48,000 $57,000 $280,000 $1,100,000
60 to <65 $9,400 $110,000 $190,000 $930,000 $4,800,000
Number Needed to Vaccinate,
GSK
20Two Year Timeframe
57
669
1,128
5,639
28,919
188
1,880 43
369
435
2,176
8,503
73
725
 - 5,000 10,000 15,000 20,000 25,000 30,000 35,000Number Needed to Vaccinate
 age 60 to <65 years age ≥65 years
Net Cost per Outcome Averted,
GSK
21Two Year Timeframe
Age-based vaccination recommendation: ≥65 years
GSK vaccine cost: $270Outpatient ED Hospitalizations ICU Stays Deaths
≥65 years $9,300 $80,000 $94,000 $470,000 $1,800,000
60 to <65 $14,000 $170,000 $290,000 $1,400,000 $7,300,000
Summary measure(s)
Pfizer
Age-based vaccination
recommendation: ≥65 years ICER ($/QALY) ICER ($/LY)
94,673 112,806
22QALY = Quality -Adjusted Life -Year
ICER = Incremental Cost -Effectiveness Ratio
LY = Life -Year
ICER values do not depend on cohort size or uptake
$200 vaccine cost
Two Year Timeframe Age-based vaccination
recommendation: 60 to <65
years ICER ($/QALY) ICER ($/LY)
218,350 313,379
Summary measure(s)
GSK
Age-based vaccination
recommendation: ≥65 years ICER ($/QALY) ICER ($/LY)
167,301 187,853
23QALY = Quality -Adjusted Life -Year
ICER = Incremental Cost -Effectiveness Ratio
LY = Life -Year
ICER values do not depend on cohort size or uptake
$270 vaccine cost
Two Year Timeframe Age-based vaccination
recommendation: 60 to <65
years ICER ($/QALY) ICER ($/LY)
372,656 478,947
Results: Sensitivity analyses,
•Tornado Diagrams
–one parameter varied at a time
•Age and Vaccine Cost
•Vaccine Duration
24
Sensitivity analyses, Pfizer
Tornado Diagram
25$200 vaccine cost
Two Year Timeframe
Age-based vaccination recommendation: ≥65 years, VE=Vaccine Efficacy LRTD= Lower Respiratory
Tract Disease, S1=Season 1, S2=Season 2.$0 $50,000 $100,000 $150,000 $200,000
Vaccine Cost
VE against hospitalization and ED S2
Incidence of RSV hospitalization
VE against hospitalization and ED S1
Cost per Hospitalization
Outpatient QALYs Lost, Adult
Incidence of outpatient visits for RSV
Mortality, adults hospitalized with RSV
VE against oupatient illness S2
ED IncidenceICERAge ≥65
Low Assumption High Assumption
Sensitivity analyses, GSK
Tornado Diagram
26$270vaccine cost
Two Year Timeframe
Age-based vaccination recommendation: ≥65 years, VE= Vaccine Efficacy, LRTD= Lower Respiratory
Tract Disease, S1=Season 1, S2=Season 2.$0 $50,000 $100,000 $150,000 $200,000 $250,000 $300,000
Incidence of RSV hospitalization
VE against hospitalization and ED S2
Vaccine Cost
Outpatient QALYs Lost, Adult
Cost per Hospitalization
VE against hospitalization and ED S1
Incidence of outpatient visits for RSV
Mortality, adults hospitalized with RSV
VE against oupatient illness S2
ED IncidenceICERAge ≥65
Low Assumption High Assumption
 $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000 $500,000
 $150  $175  $200  $225  $250  $275  $300  $325  $350ICER
Vaccine Cost
Age 60-64 age ≥65 yearsSensitivity analysis: Vaccine
Cost, Pfizer
27Two Year Timeframe
 $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000 $500,000
 $150  $175  $200  $225  $250  $275  $300  $325  $350ICER
Vaccine Cost
Age 60-64 age ≥65 yearsSensitivity analysis: Vaccine
Cost, GSK
28Two Year Timeframe
0%20%40%60%80%100%
0 20 40Efficacy
MonthAgainst medically-attended RSV-
LRTI/LRTD (hospitalization and ED)
Base Shorter Longer0%20%40%60%80%100%
0 20 40Efficacy
MonthAgainst medically-attended RSV-
LRTI/LRTD (hospitalization and ED)
Base Shorter LongerPfizer GSKVaccine Efficacy Duration
Scenarios
29
Sensitivity analyses, Pfizer:
Varying Duration of Efficacy
 $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000 $500,000
 $150  $175  $200  $225  $250  $275  $300  $325  $350ICER
Vaccine Cost
Pfizer Base age ≥65 years
Pfizer Zero Efficacy after 14 months age ≥65 years
Pfizer Zero Efficacy after 36 months age ≥65 years
30Age-based vaccination recommendation: ≥65 years
Sensitivity analyses, GSK:
Varying Duration of Efficacy
 $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000 $500,000
 $150  $175  $200  $225  $250  $275  $300  $325  $350ICER
Vaccine Cost
GSK Base age ≥65 years
GSK Zero Efficacy after 18 months age ≥65 years
GSK Zero Efficacy after 36 months age ≥65 years
31Age-based vaccination recommendation: ≥65 years
Limitations
•Model Structure
–No risk groups
–No dynamic transmission. No impact of the vaccine
on transmission and indirect effects
•Uncertain inputs
–Vaccine cost
–RSV Incidence
–Long -term efficacy
32
Summary
•Vaccination potentially Cost -Effective
•Results vary based on:
–Vaccine Cost
•ICER: 80,000 –220,000 $/QALY
–Incidence of RSV Hospitalization
•$50,000 -230,000 $/QALY
–Vaccine Efficacy
•ICER: ~80,000 -270,000 $/QALY
–Ages Vaccinated
•ICER: ~50,000 -370,000 $/QALY
–Duration of Efficacy
•ICER: ~80,000 -170,000 $/QALY33
Thank You
•Please send comments to:
•dwhutton@umich.edu
34

Summary: Economic Analysis of RSV  Vaccination in Older Adults  David W. Hutton, PhD, MS Associate Professor, Health Management and Policy, School of Public Health Associate Professor of Global Public Health, School of Public Health Associate Professor, Industrial and Operations Engineering, College of Engineering University of Michigan  Research Team University of Michigan •David Hutton, PhD •Lisa Prosser, PhD •Angela Rose, MPH •Kerra Mercon , MSCDC •Michael Melgar , MD •Mila Prill, MSPH •Jamison…


05 RSV Adults Ortega Sanchez 508

Economics of Vaccinating U.S. Adults ≥60
years -old against
Respiratory Syncytial Virus
UPDATED SUMMARY COMPARING MODELS FROM:
GSK,Pfizer AND University of Michigan -CDC
Ismael R. Ortega -Sanchez, PhD
NCIRD/CDC
ACIP Meeting, June 21, 2023
1Disclaimer : The findings and conclusions in this report are those of the authors and do not necessarily represent the views of
the Centers for Disease Control and Prevention.
National Center for Immunization & Respiratory Diseases
Conflict of interest
•GSK model : Daniel Molnar et al.,  [complete list and affiliations, upon request]
•GSK manufactures the adjuvanted RSVPreF3 vaccine
•RTI Health Solutions was funded by GSK
•Pfizer model : Derek Weycker et al., [complete list and affiliations, upon request]
•Pfizer manufacturers the bivalent RSVpreF vaccine
•Policy Analysis Inc. was funded by Pfizer
•UM-CDC model : David W Hutton et al. from Univ Michigan, …, Ismael R Ortega -
Sanchez et al. from CDC [complete list and affiliations, upon request ]
•All authors: No conflicts of interest
2
Economic analysis
Policy questions: Should adults  ≥65 years of age (or ≥60 years of age) receive
one dose of Respiratory Syncytial Virus (RSV) vaccine (GSK or Pfizer product) for
the prevention of RSV disease and its complications?
Question : Is vaccinating adults aged ≥65 years (or ≥60 years) against RSV cost-
effective ?
Comparator Intervention
Base -case scenario: What is the incremental cost-effectiveness of vaccinating adults aged
≥65 years (or ≥60 years) using RSV vaccine relative to “No vaccination”?
3Unvaccinated
≥65yr -olds
(or ≥60yr -olds)Vaccinating
≥65yr -olds
(or ≥60yr -olds)
Focus on key features for model comparison
•Modeling approach
•Targeted population(s)
•Perspective (healthcare vs. societal)
•Intervention strategy and comparator
•Inputs for RSV disease burden, vaccine efficacy, and costs
•Incidence of RSV disease, rates of outcomes
•Direct and indirect costs of RSV disease
•Intervention: Vaccine efficacy , duration of protection , safety and program
costs
•Assumptions
•Strong, influential assumptions
4Note : For this and all slides, to specifically identify changes and updates from those presented last February 2023, the text wil l
appear either highlighted, marked in red or with the word updated at the top of the slide or table.
5Modeling design and assumptions
GSK Pfizer UM-CDC
Static analytical decision -making models ✔ ✔ ✔
Sensitivity analyses (and probabilistic simulation)✔(✔)✔(✔)✔
Hypothetical population ≥65yrs -old (and ≥60 -yrs-old) ✔(✔)✔(✔)✔(✔)
Time Frame: at least 2 yr. after a dose of RSV vaccine✔ ✔ ✔
Analytic Horizon: Age -specific Life Expectancy✔ ✔ ✔
Discount rate: 3% ✔ ✔ ✔
Year of economic outcomes measured: 2022 ✔ ✔ ✔
Societal perspective (and healthcare perspective)✔(✔)✔(✔)✔(✔)
6Inputs and main outcomes
Prevention of:
•Outpatient visits for RSV
•RSV hospitalizations
•RSV-associated deaths
QALYs saved
$/QALY saved
Number needed to
vaccinate (NNV) to avert an:
•Outpatient visit for RSV
•RSV hospitalization
•RSV-associated death
GSK
UpdatedPfizer
UpdatedUM-CDC
Updated
✔ ✔ ✔
✔ ✔ ✔
✔ ✔ ✔
✔ ✔ ✔
✔ ✔ ✔
✔ ✔ ✔
✔ ✔ ✔
✔ ✔ ✔
HCRU = health care resource use
GSK, Pfizer and UM-CDC models comparison:
Selected outcome ratios for RSV vaccines (Feb 2023)
7UM-CDC
model
Vac Price
$100GSK
model
Vac Price
$148
$ / QALY gained
Vaccinating adults ≥65 yrs. 180,720 68,489
Vaccinating adults ≥60 yrs. 229,895 78,971
$ / hospitalization averted
Vaccinating  adults ≥65 yrs. 101,406 57,114
Vaccinating adults ≥60 yrs. 133,992 69,638GSK vaccine
UM-CDC
model
Vac Price
$100Pfizer
model
Vac Price
$200
$ / QALY gained
Vaccinating adults ≥65 yrs. 189,407 43,749
Vaccinating adults ≥60 yrs. 233,779 50,197
$ / hospitalization averted
Vaccinating  adults ≥65 yrs. 122,886 19,845
Vaccinating adults ≥60 yrs. 161,310 23,271Pfizer vaccine
GSK, Pfizer and UM-CDC models comparison:
Selected outcome ratios for RSV vaccines (June 2023)
8UM-CDC
model
Vac Price
$270GSK
model
Vac Price
$270
$ / QALY gained
Vaccinating adults ≥65 yrs. 167,301 55,088
Vaccinating adults ≥60 yrs. 205,638 64,348
$ / hospitalization averted
Vaccinating adults ≥65 yrs. 94,375 43,456
Vaccinating adults ≥60 yrs. 120,056 53,644GSK vaccine
UM-CDC
model
Vac Price
$200Pfizer
model
Vac Price
$200
$ / QALY gained
Vaccinating adults ≥65 yrs. 94,673 19,585
Vaccinating adults ≥60 yrs. 118,735 23,921
$ / hospitalization averted
Vaccinating  adults ≥65 yrs. 56,571 8,797
Vaccinating adults ≥60 yrs. 75,382 10,982Pfizer vaccine
$50 $100 $150 $200
Vaccine Cost
VE against hospitalization and ED S2
Incidence of RSV hospitalization
VE against hospitalization and ED S1
Cost per Hospitalization
Outpatient QALYs Lost, Adult
Incidence of outpatient visits for RSV
Mortality, adults hospitalized with RSV
VE against oupatient illness S2
ED Incidence
Low Assumption High Assumption
$50 $100 $150 $200 $250 $300
Incidence of RSV hospitalization
VE against hospitalization and ED S2
Vaccine Cost
Outpatient QALYs Lost, Adult
Cost per Hospitalization
VE against hospitalization and ED S1
Incidence of outpatient visits for RSV
Mortality, adults hospitalized with RSV
VE against oupatient illness S2
ED IncidenceGSK: $/QALY gained (thousands)
Low Assumption High AssumptionUM-CDC model : Updated One-way Sensitivity Analyses
Base case: Age ≥65yrs; $1 67,301/QALY (GSK), $94,673/QALY (Pfizer)
9Vaccine cost per dose $270/dose (GSK) , $200/dose (Pfizer)
Two-year time frame
Age-based vaccination recommendation: ≥65 years, VE=Vaccine Efficacy LRTD= Lower Respiratory Tract Disease, S1=Season 1, S2=Seas on 2.
GSK model : Updated One-way Sensitivity Analyses
Base case: Age ≥60 years; $ 64,348 /QALY saved*
10* GSK base -case vaccine price = $270/dose, three -year time frame
Average annual incidence of first RSV ARI event
Percentage of RSV LRTD cases resulting in hospitalization
Efficacy against RSV LRTD: Waning rates first vaccination with RSVPreF3 vaccine <36 months
RSVPreF3 vaccine: Peak % efficacy after first vaccination against RSV LRTD caused by first RSV infection
Probability of death given RSV LRTD
Vaccination costs per administered dose with RSVPreF3 vaccine -Purchase cost per dose –Cost
Proportion RSV LRTD within first RSV ARI event
Baseline QALYs -General population
Efficacy against RSV ARI: Waning rates first vaccination with RSVPreF3 vaccine <36 months
RSVPreF3 vaccine: Peak % efficacy after first vaccination against first RSV ARI event
Direct cost per RSV LRTD event @ 1stinfection -Unvaccinated

Pfizer model : Updated One-way Sensitivity Analyses
Base case: Age≥60 years: $23,921/QALY saved*
11Base case
* Pfizer base -case vaccine price = $200/dose,  RSV -H= RSV -associated hospitalization
GSK, Pfizer and UM-CDC models comparison:
Selected inputs
12•RSV-hospitalization rate
GSK: Proportion of medically attended RSV hospitalized cases identified by PCR, differentiated by age
(Belongia, 2018)
Pfizer : Differentiated by age and comorbidity profile (Pfizer data on file)
CDC: Differentiated by age (four RSV seasons in CDC RSV -NET data )
•Initial VE & waning over time: (updated data from GSK’s & Pfizer’s phase 3)
GSK: VE peaks in month 2, wanes linearly, reaching 0% at 34 or 43mos (depending on outcome)
Pfizer: VE is flat 7mos, wanes linearly thereafter, reaches 0% at 24mos
CDC: Step -wise: VE flat 7mos, partial drop & flat 7 -14mos ( Pfizer), 7 -18mos (GSK), reaches 0% at 24mos
•Unitary medical cost of RSV outcomes
GSK: Age -& outcome specific cost for symptomatic RSV LRTD & URTI cases (medically attended and
non-medically attended) (data from Centers for Medicare and Medicaid Services)
Pfizer: Age-, outcome -& comorbidity -specific cost for medically attended RSV illness
CDC: Age -& outcome -specific cost for medically attended RSV illness
ARI = acute respiratory infection
LRTD = lower respiratory tract disease
URTI = upper respiratory tract illness
13UM-CDC GSK Pfizer
Incidence of RSV outpatient illness
(per 100,000 persons per year)2,278
(base -case for adults ≥65 years)a1,348
(for adults ≥65 years)b2,430
(base case for adults
≥65 years)c
Incidence of RSV hospitalization
(per 100,000 persons per year)162
(base -case for adults ≥65 years)d256.3
(for adults ≥65 years)b,e300
(base -case for adults
≥65 years)c
Direct medical costs per RSV
hospitalization$21,417 –$22,425
(age -dependent)f$13,112 –$26,224
(age -dependent)g,h$12,048 –$38,380
(age -and comorbidity -
dependent)h,i
a McLaughlin et al. Open Forum Infect Dis (2022): https://doi.org/10.1093/ofid/ofac300
b Adapted from Belongia et al. Open Forum Infect Dis (2018): https://doi.org/10.1093/ofid/ofy316
c Adapted from McLaughlin et al. Open Forum Infect Dis (2022): https://doi.org/10.1093/ofid/ofac300 ; Ramirez et al. Infect Dis Ther (2023): https://doi.org/10.1007/s40121 -023-00805 -1
d RSV-NET, CDC unpublished data. Age -specific hospitalization rate per 100,000: 65.5 (60 to <65yrs), 93.8 (65 to <70yrs), 118.7 (7 0 to <75yrs) and 302.9 (75+yrs). Crude surveillance rates were
upwardly adjusted 1.5x due to incomplete case detection from reliance on upper respiratory RT -PCR (McLaughlin et al. Open Forum Infect Dis (2022): https://doi.org/10.1093/ofid/ofac300
e Adapted from Falsey et al. NEJM (2005): https://doi.org/10.1056/nejmoa043951 ; Herring et al. Vaccine (2022): https://doi.org/10.1016/j.vaccine.2021.12.002
f Ackerson et al. J Infect Dis (2020). Updated to Q3 2022$ using GDP Deflator: https://doi.org/10.1093/infdis/jiaa183 ; Branche et al. Clin Infect Dis (2022): https://doi.org/10.1093/cid/ciab595
g CMS Medicare Inpatient Hospitals (DRG Average Payments from 2019 dataset)
h Kaiser Family Foundation (How much more than Medicare do private insurers pay? 2020): https://www.kff.org/medicare/issue -brief/how -much -more -than -medicare -do-private -insurers -
pay-a-review -of-the-literature/
i Merative MarketScan Commercial Claims and Encounters (CCAE) and Medicare Supplemental Coordination of Benefits (MDCR) Databases (2016 -2019)GSK, Pfizer and UM-CDC models: Key differences in
model inputs
UM-CDC model : Sensitivity of Cost per QALY saved to RSV -Related
Hospitalization Rates among Adults ≥65 years: 2-year timeframe
14Base case for Pfizer and GSK are shown with blue and orange solid filled diamond markers, respectively : Estimated using the adjusted mean RSV -related hospitalization rate over RSV seasons: 2015 -16,
2016 -17, 2017 -18, and 2018 -19. Adjusted rate for lower sensitivity of PCR testing. CDC RSVnet
Blue ball markers : Estimated usin g Pfizer vaccine VE and price input data for the specific hospitalization rate as reported by the reference .
Orange ball markers : Estimated usin g GSK vaccine VE and price input data for the specific hospitalization rate as reported by the reference .
Labels in markers: They refer to the specific source of the RSV -associated hospitalization rate used in the estimation of either vaccine cost per QALY saved. Parentheses include either the year of the
publication or the place where the data for the study was collected.  Pfizer BasePfizer Branche (Rochester)
Pfizer Branche (NYC)
Pfizer Belongia
Pfizer Widmer (2012)Pfizer Widmer (2014)GSK BaseGSK Branche (Rochester)
GSK Branche (NYC)
GSK Belongia
GSK Widmer (2012)GSK Widmer (2014)
 $- $40,000 $80,000 $120,000 $160,000 $200,000 $240,000
 -  50  100  150  200  250  300Incremental cost per QALY gained
RSV-related hospitalization rate per 100,000
UM-CDC model : Sensitivity of Cost per QALY saved to RSV -Related
Hospitalization Rates among Adults ≥65 years: 2-year timeframe
15Pfizer BasePfizer Branche (Rochester)
Pfizer Branche (NYC)
Pfizer Belongia
Pfizer Widmer (2012)Pfizer Widmer (2014)GSK BaseGSK Branche (Rochester)
GSK Branche (NYC)
GSK Belongia
GSK Widmer (2012)GSK Widmer (2014)
 $- $40,000 $80,000 $120,000 $160,000 $200,000 $240,000
 -  50  100  150  200  250  300Incremental cost per QALY gained
RSV-related hospitalization rate per 100,000
Base case for Pfizer and GSK are shown with blue and orange solid filled diamond markers, respectively : Estimated using the adjusted mean RSV -related hospitalization rate over RSV seasons: 2015 -16,
2016 -17, 2017 -18, and 2018 -19. Adjusted rate for lower sensitivity of PCR testing. CDC RSVnet
Blue ball markers : Estimated usin g Pfizer vaccine VE and price input data for the specific hospitalization rate as reported by the reference .
Orange ball markers : Estimated usin g GSK vaccine VE and price input data for the specific hospitalization rate as reported by the reference .
Labels in markers: They refer to the specific source of the RSV -associated hospitalization rate used in the estimation of either vaccine cost per QALY saved. Parentheses include either the year of the
publication or the place where the data for the study was collected.
UM-CDC model : Sensitivity of Cost per QALY saved to RSV -Related
Hospitalization Rates among Adults ≥65 years: 2-year timeframe
16Pfizer BasePfizer Branche (Rochester)
Pfizer Branche (NYC)
Pfizer Belongia
Pfizer Widmer (2012)Pfizer Widmer (2014)GSK BaseGSK Branche (Rochester)
GSK Branche (NYC)
GSK Belongia
GSK Widmer (2012)GSK Widmer (2014)
 $- $40,000 $80,000 $120,000 $160,000 $200,000 $240,000
 -  50  100  150  200  250  300Incremental cost per QALY gained
RSV-related hospitalization rate per 100,000$55.1K, GSK (3-yr TF)
$19.6K, Pfizer
Base case for Pfizer and GSK are shown with blue and orange solid filled diamond markers, respectively : Estimated using the adjusted mean RSV -related hospitalization rate over RSV seasons: 2015 -16,
2016 -17, 2017 -18, and 2018 -19. Adjusted rate for lower sensitivity of PCR testing. CDC RSVnet
Blue ball markers : Estimated usin g Pfizer vaccine VE and price input data for the specific hospitalization rate as reported by the reference .
Orange ball markers : Estimated usin g GSK vaccine VE and price input data for the specific hospitalization rate as reported by the reference .
Labels in markers: They refer to the specific source of the RSV -associated hospitalization rate used in the estimation of either vaccine cost per QALY saved. Parentheses include either the year of the
publication or the place where the data for the study was collected.
UM-CDC model : Sensitivity of Cost per QALY saved to RSV -Related
Hospitalization Rates among Adults ≥65 years: 2-year timeframe
17Pfizer BasePfizer Branche (Rochester)
Pfizer Branche (NYC)
Pfizer Belongia
Pfizer Widmer (2012)Pfizer Widmer (2014)GSK BaseGSK Branche (Rochester)
GSK Branche (NYC)
GSK Belongia
GSK Widmer (2012)GSK Widmer (2014)
 $- $40,000 $80,000 $120,000 $160,000 $200,000 $240,000
 -  50  100  150  200  250  300Incremental cost per QALY gained
RSV-related hospitalization rate per 100,000$70.1K, GSK (2-yr TF)
$19.6K, Pfizer
Base case for Pfizer and GSK are shown with blue and orange solid filled diamond markers, respectively : Estimated using the adjusted mean RSV -related hospitalization rate over RSV seasons: 2015 -16,
2016 -17, 2017 -18, and 2018 -19. Adjusted rate for lower sensitivity of PCR testing. CDC RSVnet
Blue ball markers : Estimated usin g Pfizer vaccine VE and price input data for the specific hospitalization rate as reported by the reference .
Orange ball markers : Estimated usin g GSK vaccine VE and price input data for the specific hospitalization rate as reported by the reference .
Labels in markers: They refer to the specific source of the RSV -associated hospitalization rate used in the estimation of either vaccine cost per QALY saved. Parentheses include either the year of the
publication or the place where the data for the study was collected.
GSK, Pfizer and UM-CDC:  Initial or Early Peak of
Vaccine Efficacy & Decline in Season 2 ( updated )
18a VE over median (GSK) or mean (Pfizer) 7 months for season 1, VE through a median 18 months (GSK) or 14 months (Pfizer) for season 2 as reported in the follow up in phase 3 clinical trials
b Manufacturer phase 3 trial data; VE against medically attended acute respiratory illness
c GSK phase 3 trial data; VE against acute respiratory illness, regardless of whether medically attended. Reported peak value atmonth 2.
d GSK phase 3 trial data; VE against medically attended lower respiratory tract disease
e Pfizer phase 3 trial data; VE against medically attended lower respiratory tract illness with ≥3 lower respiratory symptoms
f GSK phase 3 trial data; VE against lower respiratory tract disease, regardless of whether medically attended. Reported peak value at month 2.UM-CDC Model GSK Model Pfizer Model
GSK vaccine Pfizer vaccine GSK vaccine Pfizer vaccine
Vaccine efficacy (VE) against RSV
outpatient illnessa Season 179.0
(54.3 –91.5)b65.2
(36.0 –82.0)bSeason 1 Peak: 74.2
(56.4 –94.0)
Weighted linear regression
over time of estimated
efficacy from clinical trialc65.1
(35.9 –82.0)b
Season 227.8
(0 –60.4)b55.0
(0 –82.0)b55.0
(95% CI: -3.4–82.0)b
VE against RSV hospitalization and
emergency department visitaSeason 187.5
(58.9 –97.6 )d84.6
(32.0 –98.3)eSeason 1 Peak: 88.0
(65.8 –99.2)
Weighted linear regression
over time of estimated
efficacy from clinical trialf84.6
(32.0 –98.3)e
Season 252.9
(0 –81.2)d75.0
(0 –97.4)e75.0
(95% CI: -25.3 –97.4)e
GSK, Pfizer and UM-CDC: Assumption on waning of
vaccine efficacy (VE) per outcome ( Feb 2023 )
19GSKVE peaks at 2 months then wanes per month
RSV-ARI = 5.36% points per month (range: 0.00 -
13.37%)
RSV-LRTD = 2.63% points per month (range: 0.00 -
10.95%)
No residual protection after 12 monthsPfizerInitial VE assumed to persist for 7 months,
Then to decline linearly to 0% effectiveness at 24
months
Residual though declining protection up to 24
monthsUM-CDCVaccine and outcome -specific
For both vaccines:
Exponential decay up to 12 months
and then 0% afterwards; calibrated such that the
first 6 months VE equals the trial estimate

GSK, Pfizer and UM-CDC: Assumption on waning of
vaccine efficacy (VE) per vaccine & outcome ( June 2023 )
20
GSK
UM-CDC UM-CDC
The pink -shaded areas denote a higher level of uncertainty of the waning assumption beyond available phase 3 data
Feb 2023GSK: Residual Vaccine Effectiveness (Feb 2023
ACIP) and updated analyses ( June 2023 )
21RSV LRTD : 50% of peak VE ( 88% )
assumed in month 1, peak VE
declines by 2.10% (2.63% in Feb)
monthly rate beginning in month 2
though 20-month maximum follow
up of trial .  Assumed to follow
linear decline trend afterwards.
Reaches 0% in month 43
RSV ARI : 50% of peak VE ( 74% )
assumed in month 1, peak VE
declines by 2.26% (5.36% in Feb)
monthly rate beginning in month 2
though 20-month maximum follow
up of trial .  Assumed to follow
linear decline trend afterwards.
Reaches 0% in month 34
The pink -shaded area denotes a higher level of uncertainty of the waning assumption beyond
available phase 3 data
Pfizer : Residual Vaccine Effectiveness (Feb
2023 ACIP) and updated analyses ( June 2023 )
22
Hospitalization or ED : Initial
VE (84.6%) assumed to
persist for 7 months, to
decline to 75% at 14 months,
and then decline to 0% at
24thmonth
Outpatient : Initial VE ( 65.1% )
assumed to persist for 7
months, to decline to 55% at
14 months, and then decline
to 0% at  24thmonth
The pink -shaded area denotes a higher level of uncertainty of the waning assumption beyond
available phase 3 data
UM-CDC: Updated assumption on waning of
vaccine efficacy per vaccine and outcome
23Hospitalization or ED: Initial VE (87.5%
GSK; 84.6% Pfizer ) assumed to persist
for 7 months, to drop to 52.9% ( GSK),
75%( Pfizer) and remain flat from
month 8 to month 18 ( GSK) or month
14 (Pfizer ), and then decline linearly to
0% at month 24.
Medically attended (Outpatient):
Initial VE (79% GSK; 65.2% Pfizer )
assumed to persist for 7 months, to
drop to 27.8% ( GSK), 55%( Pfizer ) and
remain flat from month 8 to month 18
(GSK), month 14 ( Pfizer ), and then
decline linearly to 0% at month 24
GSK
Pfizer87.5%
52.9%79.0%
27.8%
84.6%
75.0%
65.2%
55.0%
The pink rectangle highlights the difference in duration of protection assumption between vaccines
Comparison of GSK and Pfizer vaccines: Update base
case & scenario $/QALY results using UM-CDC model
24aIncidence rates: Lower incidence assumes 95% RT -PCR test sensitivity, Higher rate incorporates the upper limit of the 95% CI ar ound the base case incidence rate
estimate.
b Recommendation = vaccination at age ≥65 years; incidence rates of RSV outcomes upwardly adjust 1.5x to account for incomple te RT-PCR sensitivity on a
respiratory specimen (McLaughlin et al; Open Forum Infect Dis 2022); vaccine efficacy only considered for two years post -vaccina tionScenario GSK Pfizer
Vaccinating adults aged 60 to <65 years only $372,656 $218,250
Lower incidence of RSVain adults ≥65 years $276,393 $161,487
Vaccine cost $340 per dose $220,864 $187,865
Vaccinating adults ≥60 years, $205,638 $118,735
Residual vaccine protection = 0% at 18 (GSK) or 14 (Pfizer) months $170,022 $135,886
Base caseb(Vacc price $270 GSK, $200 Pfizer , adults ≥65yrs) $167,301 $94,673
Vaccine cost $180 per dose $98,485 $81,358
Higher incidence of RSVbin adults ≥65 years $84,736 $40,467
Limitations
25•Factors not considered that may result in overestimating the ICER
(underestimating the cost -effectiveness) of RSV vaccination
•All of the 3 models assumed no indirect effects of vaccination (i.e., no protection against RSV
transmission)
Except UM-CDC model
•Manufacturers models do not include RSV -related medical costs incurred after discharge
from an RSV -associated hospitalization or emergency department visit:
•Stay in long -term care or rehabilitation facility
•Manufacturers models do not include potential vaccine -associated serious
adverse events (SAEs)
•Quality of life impact, resource utilization and costs associated with hypothetical SAEs
•Vaccine efficacy beyond clinical trial follow -up time (beyond 14 months, Pfizer
or 18 months, GSK) is unknown
•All 3 models assumed non -zero declining efficacy beyond 14 or18 months
Conclusion
26•Differences in key inputs among GSK, Pfizer and UM-CDC models explain differences in results:
•Annual incidence of RSV hospitalization and outpatient disease
•Initial vaccine (season 1) and waning of protection (VE season 2+)
•Selection of medical costs sources and data extraction approach
•Resulting ICERs depended heavily on assumptions and selection of input data
•Annual incidence of RSV Hospitalization
•Vaccine costs (e.g., increase in GSK vaccine price)
•Base -case in the 3 models:
•Vaccination would significantly reduce RSV disease burden in older adults
•VE clinical trials data and assumptions support impact on disease reduction
•Economic value of RSV vaccines appear to be costly and could be cost-effective
•RSV incidence, related healthcare costs, initial VE and duration combined with reasonable
vaccine price would determine the cost-effectiveness value of RSV vaccination
Acknowledgements
From NCIRD/CDC
•Michael Melgar
•Jamison Pike
•Fiona Havers
•Amadea Britton
Also:
•Adult RSV working group members
•Andrew Leidner and the Econ Team members at ISD/NCIRD
27

Summary: Economics of Vaccinating U.S. Adults ≥60  years -old against  Respiratory Syncytial Virus UPDATED SUMMARY COMPARING MODELS FROM: GSK,Pfizer AND University of Michigan -CDC Ismael R. Ortega -Sanchez, PhD NCIRD/CDC ACIP Meeting, June 21, 2023 1Disclaimer : The findings and conclusions in this report are those of the authors and do not necessarily represent the views of  the Centers for Disease Control and Prevention.  National Center for Immunization & Respiratory Diseases Conflict of interest…