RSV Pediatric 05 Jones 508

Centers for Disease Control and Prevention
Draft Interim Clinical Considerations:
Nirsevimab
Jefferson Jones MD MPH FAAP , CDR USPHS
ACIP General MeetingFebruary 23, 2023
162Goals of recommendations
Provide simple, uniform recommendations that apply to most U.S. health
care providers
Provide flexibility for specific situations
163Policy Question
Should one dose of nirsevimab be recommended a) at birth for all
infants born during October to March and b) when entering first RSV
season and <8 months of age for all infants born during April through
September?
164Important considerations for timing of administration
Efficacy beyond 150 days is unknown
Majority of infants will only be eligible for a single dose of nirsevimab
Only 1 dose is recommended per season
If nirsevimab given too early, efficacy might wane during the RSV season
For infants born during October –March, the optimal timing of nirsevimab
dosing is at birth
For infants born during April -September, the ideal timing for nirsevimab
dosing is just before or near the start of the RSV season
165Timing and location of nirsevimab administration
For infants born during Oct–Mar, shortly after birth or as soon as possible
–Administration in hospital prior to discharge would be optimal to
ensure early protection
–If not given prior to discharge, administration at first visit to primary care provider, ideally within 1 week of discharge
For infants born Apr –Sep
–Nirsevimab administration recommended during Oct- Nov (e.g., during
regularly scheduled 2- , 4-, or 6- month well child visits)
166Additional considerations
During COVID-19 pandemic, interseasonal RSV transmission has
occurred
Work Group has expressed it is important to allow for flexibility of
timing in nirsevimab administration during periods of significant
interseasonal RSV transmission
During 2023 -2024 season, nirsevimab may not be available prior to
October 2023
167RSV-associated hospitalization rates in children aged
0-11 months, New Vaccine Surveillance Network
0 1 2 3 4 5 6 7 8 9 10 11
2000-2005 13.5 25.9 14.3 10.3 8.9 4.8 4.1 5.6 3.4 3.8 3.7 2.9
2016-2020 17.6 31.1 22.3 15.6 13.6 10.9 9.6 8.0 7.3 8.4 6.0 6.00510152025303540Hospitalization rate per 1000
Age in months2000-2005 2016-2020
2000 -2005: Adapted from Hall et al, Pediatrics 2013; 2016 -2020: CDC unpublished data
168Timing of beginning nirsevimab administration
If increased RSV transmission is occurring locally in August or September,
nirsevimab could be administered to eligible infants earlier than October, if available
Local epidemiology data may be best indicator but recommend establishing evidence -based threshold
National Respiratory and Enteric Virus Surveillance System (NREVSS)
–May be used as one source of evidence
–Census Division- level or HHS regional -level data recommended1
–In NREVVS, >3% percent positivity of PCR tests for 2 consecutive weeks can indicate increased level of RSV detections
https://www.cdc.gov/surveillance/nrevss/index.html1Data from a single state may not be representative and should be interpreted with caution
169Timing of ending nirsevimab administration
To determine if nirsevimab should continue to be administered to newborns shortly
after birth beyond March, l ocal jurisdictions can alter administration schedules based on
local transmission conditions with clear evidence of ongoing increased transmission
–Local data may be best indicator but recommend establishing evidence -based
threshold
–NREVSS
•May be used as one source of evidence
•Census Division- level or HHS Region- level data recommended1
•For NREVVS data, <5% percent positivity of PCR tests for 2 consecutive weeks
can indicate decreasing transmission
https://www.cdc.gov/surveillance/nrevss/rsv/index.html1Data from a single state may not be representative and should be interpreted with caution
170Tropical climates
Tropical climates (e.g., Hawaii, Guam, and US -affiliated Pacific Islands)
may have RSV seasonality that differs from most of the continental US
or is unpredictable
Nirsevimab administration recommended to newborns shortly after
birth throughout the year
Certain jurisdictions with tropical climates (e.g., Puerto Rico)
recommend birth dose nirsevimab administration d uring Aug– Mar. For
infants born Apr -July, recommended in Aug –Sep.
Consult with local, state, or territorial health department for
recommendations
171Alaska
In Alaska, RSV seasonality is less predictable, and the duration of RSV
activity is often longer than the national average
–Providers are advised to use RSV laboratory surveillance data generated by the state of Alaska to assist in determining the appropriate timing of
nirsevimab
The Alaska Department of Health will continue to provide clinicians with
updated Alaska -specific guidance
172Infants residing in remote areas
Infants born during April– September and residing in remote areas (e.g.,
would require medical evacuation by air for severe disease) can be
given nirsevimab as early as August if there is concern that the infant
may not have access to nirsevimab at th e recommended time (Oct–
Nov)
173Policy question
Should one dose of nirsevimab be recommended for children
<20 months of age entering their second RSV season who are eligible
for palivizumab in their second RSV season?
174Population recommended for nirsevimab when
entering 2nd RSV season
Same groups eligible for palivizumab when entering 2nd RSV season per American
Academy of Pediatrics recommendations
–Children with chronic lung disease of prematurity if require medical support (chronic corticosteroid therapy, diuretic therapy, or supplemental oxygen) during the 6- month period before the start of the second RSV season
–Children who are profoundly immunocompromised
–Children with cystic fibrosis with manifestations of severe lung disease
(previous hospitalization for pulmonary exacerbation in the first year of life or abnormalities on chest XR or CT that persist when stable) or weight for length < 10th percentile
Other conditions are under review
American Academy of Pediatrics Committee on Infectious Diseases and Bronchiolitis Guidelines Committee. Updated guidance for palivizumab prophylaxis among
infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics. 2014 A ug;134(2):415 -20.
175Timing of nirsevimab administration for 2ndRSV
season
Nirsevimab should be administered during October to November
Nirsevimab is not recommend to be used after the 2nd RSV season
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.

Summary: Centers for Disease Control and Prevention Draft Interim Clinical Considerations:  Nirsevimab Jefferson Jones MD MPH FAAP , CDR USPHS ACIP General MeetingFebruary 23, 2023 162Goals of recommendations Provide simple, uniform recommendations that apply to most U.S. health  care providers Provide flexibility for specific situations 163Policy Question Should one dose of nirsevimab be recommended a) at birth for all  infants born during October to March and b) when entering first RSV  season and…


RSV Pediatric 06 Munjal 508

MedicalSafety and Efficacy of
Bivalent RSV Prefusion F Vaccine
in Vaccinated Mothers and their Infants
Iona Munjal, MD
Senior Director, Vaccine Research and Development

178Worldwide Research, Development and Medical
Vaccine Research and DevelopmentBivalent RSV Prefusion F Vaccine
Proposed Indication:
Prevention of lower respiratory
tract disease and severe lower
respiratory tract disease caused by
respiratory syncytial virus (RSV)DOSE LEVEL•120 µg without an adjuvant
•Dose contains 60 µg dose of
each prefusion protein
antigen, in a 0.5 mL injection
PRESENTATION•Single dose 2 mL vial
•1 mL Pre-filled syringe
•Vial adaptor
STORAGE •Refrigeration at 2 °Cto 8°CInfants from birth through 6 months of age by active immunization of pregnant individuals
179Worldwide Research, Development and Medical
Vaccine Research and DevelopmentGroundbreaking Structural Work by NIH Elucidated that RSV F on the
Virus Exists as an Unstable Prefusion Form
Only prefusion F can bind host
cells for RSV to infect
Antibodies specific to the
prefusion form are most effective
at blocking virus infection
McLellan et al. Science, Nov 2013
Postfusion F Trimer
fused membranePrefusion F Trimer
Antigenic Site Ø
(Nirsevimab, AM22)
Viral membraneAntigenic Site II
(Synagis)
Antigenic Site IV
(101- F, AM14)

180Worldwide Research, Development and Medical
Vaccine Research and Development2018 2019 2020 2021 2022+
Phase 1/2
First -in-Human1Adults 18- 85y
Dose Ranging
+/-Al(OH)3 +/-Influenza
Phase 2b2Pregnant Women 18–49y
Safety and ImmunogenicityEarly Efficacy
Phase 2b
3 Nonpregnant Women 18– 49y
Concomitant Tdap
Phase 34 Adults 18- 49y
Lot Consistency Study
Phase 35 Pregnant Women ≤49y
Pivotal Efficacy
1. A Study to Describe the Safety and Immunogenicity of a RSV Vaccine in Healthy Adults. NCT03529773.
2. A Phase 2bPlacebo- Controlled, Randomized Study of an RSV Vaccine in Pregnant Women. NCT04032093.
3. A Study of an RSV Vaccine When Given Together with Tdap in Healthy Nonpregnant Women Aged Between 18 to 49 Years. NCT04071158.
4. Clinical Lot Consistency for RSVpreF in a Population of Healthy Adults 18 to ≤49 Years of Age. NCT05096208.
5. A Trial to Evaluate the Efficacy and Safety of RSVpreF in Infants Born to Women Vaccinated During Pregnancy. NCT04424316 .Pfizer’s RSVpreF Maternal Immunization Clinical Development Program

181Worldwide Research, Development and Medical
Vaccine Research and Development2018 2019 2020 2021 2022+
Phase 1/2
First -in-Human1Adults 18- 85y
Dose Ranging
+/-Al(OH)3 +/-Influenza
Phase 2b2Pregnant Women 18–49y
Safety and ImmunogenicityEarly Efficacy
Phase 2b
3 Nonpregnant Women 18- 49y
Concomitant Tdap
Phase 34 Adults 18- 49y
Lot Consistency Study
Phase 35 Pregnant Women ≤49y
Pivotal Efficacy
1. A Study to Describe the Safety and Immunogenicity of a RSV Vaccine in Healthy Adults. NCT03529773.
2. A Phase 2bPlacebo- Controlled, Randomized Study of an RSV Vaccine in Pregnant Women. NCT04032093.
3. A Study of an RSV Vaccine When Given Together with Tdap in Healthy Nonpregnant Women Aged Between 18 to 49 Years. NCT04071158.
4. Clinical Lot Consistency for RSVpreF in a Population of Healthy Adults 18 to ≤49 Years of Age. NCT05096208.
5. A Trial to Evaluate the Efficacy and Safety of RSVpreF in Infants Born to Women Vaccinated During Pregnancy. NCT04424316 .Pfizer’s RSVpreF Maternal Immunization Clinical Development Program

182Worldwide Research, Development and Medical
Vaccine Research and DevelopmentRSVpreF Elicits Maternal Neutralizing Titer with GMR >12 at Delivery*
Phase 2bCombined A/B 50% Neutralization Geometric Mean Titers & Geometric Mean Ratio vs. Placebo – in Maternal Participants at
Baseline (24- 36 weeks GA), 1M(if Delivery had not Occurred), Delivery and Postpartum; All Evaluable (N=116 participants)
10100100010000100000
Baseline 1 Month Delivery 6 Months Postpartum50% Neutralizing GMT
Placebo 120 μ g17.8
12.4 5.4
Lower Limit of Quantification (L LOQ), RSV A                 LLOQ , RSV B*Mean time from vaccination to delivery, 61.4 days
183Worldwide Research, Development and Medical
Vaccine Research and DevelopmentTransplacental Transfer Ratios >1 Overall and by Geography and
Gestational Age
Combined RSV A/B 50% Neutralization Antibody Infant v. Maternal Ratio for Phase 3 selected dose
Evaluable Population, RSVpreF Groups (N=99)
0.1110
RSV A/B, All
(n=99)Northern
Hemisphere
(n=88)Southern
Hemisphere
(n=11)GA 24 to <27
(n=21)GA 27 to <30
(n=26)GA 30 to <33
(n=26)GA 33 to 36
(n=26)Neutralizing Titer Transfer Ratio
Geography Maternal Gestational Age at Vaccination
184Worldwide Research, Development and Medical
Vaccine Research and DevelopmentRSV A/B Combined 50% Geometric Mean Neutralizing Titers by Month in Infants born to Mothers Vaccinated at 24-36 weeksInfant Neutralizing Titers Remain High Through 6 Months
100100010000100000
0 1 2 3 4 5 6 7RSV A/B Combined Serum Neutralizing
Titer
MonthsRSVpreF 120 μ g
Placebo
Palivizumab reference
---Palivizumab reference line = 50% A/B neutralizing titer of a 100ug/mL palivizumab dose, demonstrated to be efficacious in preventing infant RSV-
associated ICU admission (Forbes ML, Kumar VR, Yogev R, et al. Hum Vaccin Immunother 2014;10:2789 -94.)
185Worldwide Research, Development and Medical
Vaccine Research and Development2018 2019 2020 2021 2022+
Phase 1/2
First -in-Human1Adults 18- 85y
Dose Ranging
+/-Al(OH)3 +/-Influenza
Phase 2b2Pregnant Women 18–49y
Safety and ImmunogenicityEarly Efficacy
Phase 2b
3 Nonpregnant Women 18- 49y
Concomitant Tdap
Phase 34 Adults 18- 49y
Lot Consistency Study
Phase 35 Pregnant Women ≤49y
Pivotal Efficacy
1. A Study to Describe the Safety and Immunogenicity of a RSV Vaccine in Healthy Adults. NCT03529773.
2. A Phase 2bPlacebo- Controlled, Randomized Study of an RSV Vaccine in Pregnant Women. NCT04032093.
3. A Study of an RSV Vaccine When Given Together with Tdap in Healthy Nonpregnant Women Aged Between 18 to 49 Years. NCT04071158.
4. Clinical Lot Consistency for RSVpreF in a Population of Healthy Adults 18 to ≤49 Years of Age. NCT05096208.
5. A Trial to Evaluate the Efficacy and Safety of RSVpreF in Infants Born to Women Vaccinated During Pregnancy. NCT04424316 .Pfizer’s RSVpreF Maternal Immunization Clinical Development Program

186Worldwide Research, Development and Medical
Vaccine Research and DevelopmentA Trial to Evaluate the Efficacy and Safety of RSVpreF in Infants Born to Women Vaccinated During Pregnancy. NCT04424316.MATISSE: A Phase 3 Trial to Evaluate the Efficacy and Safety of RSVpreF in
Infants Born to Women Vaccinated During Pregnancy
7,392 Maternal Participants in 18 Countries
Randomized 1:1 RSVpreF 120µg or Placebo
Pregnant persons ≤49 years between
≥24 and ≤36 weeks gestation
7,128 Infants enrolled

187Worldwide Research, Development and Medical
Vaccine Research and Development
AEs from Consent to 28 Days
a. Screening bloods and fetal anomaly ultrasound (if not standard of care); ROW, Rest of World
b. Fetal dating and dating ultrasounds (if not standard of care).
c. AESI (AE of Special Interest including preterm delivery and asymptomatic SARS -CoV -2 test positive).Maternal Immunogenicity & Safety Assessment Timeline
AESIc, SAEs : Consent to End of Study
7 days e-diary
Screening
Philippines & Africab
Screening
ROWa
Day -90 Day -28 Day 1 Day 7 Day 28 Variable Duration Delivery 6-Months Post Delivery
RTI surveillance : All MA -RTI Events Captured as Endpoints from Vaccination to End of Study
Pre-Screening
Pre-vaccination
Vaccination
Visit 1
1-Month Follow- up
Visit 2
Labor & Delivery
Visit 3
Maternal Follow- Up
Visit 4

188Worldwide Research, Development and Medical
Vaccine Research and Development
AEs for 28 Days
Infant Efficacy, Immunogenicity & Safety Assessment Timeline
AESI, SAEs and NDCMCs: Birth to End of Study
Birth Day 1 28 Days After 6-mo 12-Mo 24-Mo
Delivery & Infant RTI Surveillance Period*
*Starts 72 hours after delivery
18-Mo
Visit 1
 Visit 2
 Visit 3
12-Mo Follow- up
for All Infants
24-mo Follow- up for Infants
Born in Study -year 1
Cord
Blood
Weekly contact with mother /
RTI site visit + nasal swabs for MA -RTI
Monthly contact with mother / RTI hospitalization
& severe LRTI requires RTI visit + nasal swabs
RTISurveillance (e-dairy)
Visit 4
 Visit 5
 Visit 6
AESI (AE of Special Interest including preterm birth, low birth weight, developmental delay, and asymptomatic SARS -CoV -2 test positive)
SAE (Serious Adverse Event)
NDCMC (Newly Diagnosed Chronic Medical Condition)
189Worldwide Research, Development and Medical
Vaccine Research and Developmenta. N = number of participants in the specified vaccine group. This value is the denominator for the percentage calculations.
b. n = Number of participants in the specified category. Demographic Characteristics
(Maternal Safety Population)
RSVpreF 120 μg
(Na=3682) ; n (%)Placebo
(Na=3675) ; n (%)Total
(Na=7357) ; n (%)
Race
White 2383 (64.7) 2365 (64.4) 4748 (64.5)
Black or African American 720 (19.6) 723 (19.7) 1443 (19.6)
Asian 454 (12.3) 464 (12.6) 918 (12.5)
American Indian or Alaskan Native 38 (1.0) 37 (1.0) 75 (1.0)
Native Hawaiian or Other Pacific Islander 9 (0.2) 12 (0.3) 21 (0.3)
Multiracial 30 (0.8) 21 (0.6) 51 (0.7)
Ethnicity
Hispanic/Latino 1049 (28.5) 1075 (29.3) 2124 (28.9)
190Worldwide Research, Development and Medical
Vaccine Research and Development*Average GA at vaccination = 30 weeks
Note: One participant is counted under ≥24 weeks to <28 weeks however actual age was 23 weeks 6 days.
a. N = number of participants in the specified vaccine group. This value is the denominator for the percentage calculations.
b. n = Number of participants in the specified category. Demographic Characteristics (continued 2/2)
(Maternal Safety Population)
RSVpreF 120 μg
(Na=3682) ; n (%)Placebo
(Na=3675) ; n (%)Total
(Na=7357) ; n (%)
Age at Vaccination (years)
N 3682 3675 7357
Mean (SD) 29.1 (5.64) 29.0 (5.74) 29.0 (5.69)
Median (Range) 29.0 (16– 45) 29.0 (14– 47) 29.0 (14– 47)
Gestational Age (GA) at Vaccination*
≥24 weeks to <28 weeks 941 (25.6) 909 (24.7) 1850 (25.1)
≥28 weeks to <32 weeks 1085 (29.5) 1128 (30.7) 2213 (30.1)
≥32 weeks to ≤36 weeks 1653 (44.9) 1632 (44.4) 3285 (44.7)
>36 weeks 3 (<0.1) 6 (0.2) 9 (0.1)
191Worldwide Research, Development and Medical
Vaccine Research and DevelopmentDemographic Characteristics
(Infant Safety Population)
RSVpreF 120 μg
(Na=3568); n (%)Placebo
(Na=3558) ; n (%)Total
(Na=7126) ; n (%)
Sex
Male 1816 (50.9) 1793 (50.4) 3609 (50.6)
Female 1752 (49.1) 1765 (49.6) 3517 (49.4)
Race
White 2294 (64.3) 2284 (64.2) 4578 (64.2)
Black or African American 687 (19.3) 688 (19.3) 1375 (19.3)
Asian 420 (11.8) 430 (12.1) 850 (11.9)
American Indian or Alaskan Native 42 (1.2) 36 (1.0) 78 (1.1)
Native Hawaiian or other Pacific Islander 13 (0.4) 11 (0.3) 24 (0.3)
Multiracial 65 (1.8) 59 (1.7) 124 (1.7)
Ethnicity
Hispanic/Latino 1033 (29.0) 1039 (29.2) 2072 (29.1)
a.N = number of participants in the specified vaccine group. This value is the denominator for the percentage calculations.
b.n = Number of participants in the specified category.
192Worldwide Research, Development and Medical
Vaccine Research and DevelopmentPhase 3 Study Objectives
Safety•Describe the safety profile of RSVpreF
Local reactions and systemic events within 7 days post -vaccination
AEs through 1-month post -vaccination (Maternal)
AEs through 1-month after birth (Infant)
AESIs , SAEs (Maternal and Infant) and NDCMCs (Infant) throughout study
EfficacyPrimary•Prevention of RSV MA -LRTI within 180 days after birth
•Prevention of RSV severe MA -LRTI within 180 days after birth
Secondary•Prevention of RSV MA -LRTIs within 360 days after birth
•Prevention of RSV hospitalization within 360 days after birth
•Prevention of MA -LRTIs due to any cause within 360 days after birth
AE, adverse event; AESI, adverse event of special interest; NDCMC, newly diagnosed chronic medical condition; SAE, serious adver se event;
MA, medically attended; LRTI, lower respiratory tract illness; RSV, respiratory syncytial virus
193Worldwide Research, Development and Medical
Vaccine Research and Development7.2%
0.2%6.2%
0.2%40.6%
10.1%
0102030405060708090100
RSVpreF
120µgPlacebo RSVpreF
120µgPlacebo RSVpreF
120µgPlacebo% of Subjects
Vaccine Group (as Administered)
 Mild  Moderate  SevereLocal Reactions, by Maximum Severity, within 7 Days After Vaccination
Maternal Participants (n=7357)
Induration/Swelling Pain at Injection Site Erythema/Redness
194Worldwide Research, Development and Medical
Vaccine Research and Development2.6% 2.9%46.1%43.8%
31.0%27.6%
20.0% 19.2%26.5%
17.1%
11.6% 10.5%7.8% 7.0%11.2% 11.5%
0102030405060708090100
RSVpreF
120µgPlacebo RSVpreF
120µgPlacebo RSVpreF
120µgPlacebo RSVpreF
120µgPlacebo RSVpreF
120µgPlacebo RSVpreF
120µgPlacebo RSVpreF
120µgPlacebo RSVpreF
120µgPlacebo% of Subjects
Vaccine Group (as Administered)
Mild or 38.0°C to 38.4°C Moderate or 38.5°C to 38.9°C Severe or 39.0°C to 40.0°C >40°CSystemic Events, by Maximum Severity, Within 7 Days After Vaccination
Maternal Participants (n=7357)
Fatigue Headache Muscle Pain Diarrhea Nausea Fever Joint Pain Vomiting
195Worldwide Research, Development and Medical
Vaccine Research and DevelopmentAbbreviations: AESIs = adverse events of special interest; NDCMCs = newly diagnosed chronic medical conditions.
Notes: The severity of the event is in the determination of the investigator. Per statistical analysis plan, 1 month after bi rthor 1 month after vaccination reflects a 30- day period. However, as per protocol, non- serious adverse events were only solicited
through 28 days after birth/vaccination. AESIs and SAEs were solicited throughout the study for maternal participants.a. N = number of participants in the specified vaccine group. This value is the denominator for the percentage calculations. b. n = Number of participants reporting at least 1 occurrence of the specified adverse event. For "any event", n = number of
participants reporting at least 1 occurrence of any adverse event. c. Exact 2- sided confidence interval (CI) calculated using the Clopper and Pearson method. d. An immediate AE is defined as any AE that occurred within the first 30 minutes after
administration of the investigational product for maternal participants.Number (%) of Participants Reporting Adverse Events by Category
Within 1 Month After Vaccination
Maternal Participantsa,b,c
13.8
4.2
<0.11.7 0.5 0.42.70.013.1
3.7<0.1 1.3 0.3 0.22.50.0
0102030405060708090100
Any AE Serious AE Immediate AEᵈ Severe AE Life-threatening
AERelated AESIs AE Leading to
WithdrawalParticipants
Reporting ≥ AE %RSVpreF 120 μg
(N=3682)
Placebo
(N=3675)
196Worldwide Research, Development and Medical
Vaccine Research and DevelopmentAbbreviations: AESIs = adverse events of special interest; NDCMCs = newly diagnosed chronic medical conditions.
Notes: The severity of the event is in the determination of the investigator. Per statistical analysis plan, 1 month after bi rthor 1 month after vaccination reflects a 30- day period. However, as per protocol, non- serious adverse events were only solicited
through 28 days after birth/vaccination. AESIs and SAEs were solicited throughout the study for maternal participants.a. N = number of participants in the specified vaccine group. This value is the denominator for the percentage calculations. b. n = Number of participants reporting at least 1 occurrence of the specified adverse event. For "any event", n = number of
participants reporting at least 1 occurrence of any adverse event. c. Exact 2- sided confidence interval (CI) calculated using the Clopper and Pearson method. d. An immediate AE is defined as any AE that occurred within the first 30 minutes after
administration of the investigational product for maternal participants.Number (%) of Participants Reporting Adverse Events by Category
Within 1 Month After Birth
Infant Participantsa,b,c
37.1
15.5
4.51.0 <0.18.44.8
0.2 0.034.5
15.2
3.81.0 0.07.2 5.9
0.2 0.0
0102030405060708090100
Any AE Serious AE Severe AE Life-threatening
AERelated AESIs Congenital
AnomaliesNDCMCs AE Leading to
WithdrawalParticipants
Reporting ≥ AE %RSVpreF 120 μg
(N=3568)
Placebo
(N=3558)
197Worldwide Research, Development and Medical
Vaccine Research and DevelopmentBirth Outcomes and Developmental Delay – Infant Participants
Infant Participants with Prematurity, Low Birth Weight, or Developmental Delay (Adverse Events of Special Interest)
0.65.6
0.15.1
0.3 0.34.7
0.24.4
0.3
0102030405060708090100
Early Premature
≤ 34 weeksTotal Premature
≤ 37 weeksVery Low Birth Weight
< 1500gLow Birth Weight
<2500gDevelopmental Delay% ParticipantsRSVpreF
(N=3568)
Placebo(N=3558)
198Worldwide Research, Development and Medical
Vaccine Research and DevelopmentDeaths and Fetal Losses Reported in the Trial (all unrelated)
Event TypeRSVpreF 120 μg
(N=3682)Placebo
(N=3675)
Maternal Death: n = 1
•1 in a maternal participant who received RSVpreF Maternal Death 1 (<0.1%) 0
Fetal Demise: n = 18
•18 fetal demises in maternal participants who received
Vaccine/PlaceboFetal death or stillbirth 10 (0.3%) 8 (0.2%)
Event TypeRSVpreF 120 μg
(N=3568)Placebo
(N=3558)
Infant Death: n = 17
•16 due to various causes
•1 infant adjudicated “Acute Respiratory Illness due to RSV” (placebo group)Infant Death 5 (0.1%) 12 (0.3%)
199 Breakthroughs that change patients’ livesMATISSE
Infant Efficacy Endpoints

200Worldwide Research, Development and Medical
Vaccine Research and DevelopmentC3671008: https://clinicaltrials.gov/ct2/show/NCT04424316?term=C3671008&draw=2&rank=1Phase 3 Efficacy Endpoints Defined
Primary Endpoints Criteria
Medically attended
RSV LRTIMedically attended visit and ≥1 :
•tachypnea (RR ≥60 (<2 m [60 days]) or ≥50 (≥2 to 12 m)
•peripheral capillary oxygen saturation (SpO2) measured in room air <95%
•chest wall indrawing
Medically attended
severe RSV LRTIMedically attended visit and ≥1 :
•tachypnea (RR ≥70 (<2 m [60 days]) or ≥60 (≥2 to 12 m)
•SpO2 measured in room air <93%
• high- flow nasal cannula or mechanical ventilation
•ICU admission for >4 hours; unresponsive/unconsciousPositive
validated
RT-PCR
in central
laboratoryWeekly active surveillance for ARI symptoms
Symptoms trigger nasal swab and possibly a visit
Medically attended visit: Infant participant taken to or seen by a healthcare provider (e.g. outpatient or inpatient visit, emer gency room, urgent care, or home visit)
LRTI : Lower respiratory tract illness; SpO2: peripheral capillary oxygen saturation
201Worldwide Research, Development and Medical
Vaccine Research and DevelopmentRSV-Positive MA -LRTI
Time Interval Number of Cases (%) Number of Cases (%) Vaccine Efficacyb(%) (CI*)
90 Days after birth 24 (0.7) 56 (1.6) 57.1 (14.7, 79.8)
120 Days after birth 35 (1.0) 81 (2.3) 56.8 (31.2, 73.5)
150 Days after birth 47 (1.3) 99 (2.8) 52.5 (28.7, 68.9)
180 Days after birth 57 (1.6) 117 (3.4) 51.3 (29.4, 66.8)Maternal Vaccine Group (as Randomized)
RSV-Positive Severe MA -LRTIRSVpreF 120 μg
(Na=3495)Placebo
(Na=3480)
Time Interval Number of Cases (%) Number of Cases (%) Vaccine Efficacyb(%) (CI*)
90 Days after birth 6 (0.2) 33 (0.9) 81.8 (40.6, 96.3)
120 Days after birth 12 (0.3) 46 (1.3) 73.9 (45.6, 88.8)
150 Days after birth 16 (0.5) 55 (1.6) 70.9 (44.5, 85.9)
180 Days after birth 19 (0.5) 62 (1.8) 69.4 (44.3, 84.1)Vaccine Efficacy by Cumulative Days after Birth for Two Primary Endpoints
*99.5% CI for 90 days, 97.58% CI for 120/150/180 days.  CI LB >20% for all time points.
Abbreviations: RSV = respiratory syncytial virus. a. N = number of participants (at risk) in the specified group. These values a re used as the denominators for the percentage calculations. b. Vaccine efficacy was
calculated as 1- (P/[1- P]), where P is the number of cases in the RSVpreF group divided by the total number of cases. The confide nce interval was adjusted using Bonferroni procedure and accounting for the primary
endpoints results.Primary Endpoints:
202Worldwide Research, Development and Medical
Vaccine Research and DevelopmentAbbreviations: MA -LRTI = medically attended lower respiratory tract illness; RSV = respiratory syncytial virus.
a. N = number of participants (at risk) in the specified group. These values are used as the denominators for the percentage calculations.
b. Vaccine efficacy was calculated as 1- (P/[1- P]), where P is the number of cases in the RSVpreF group divided by the total number of cases. The confidence interval was adjusted using Bonferroni procedure and accounting for the primary endpoints results.Secondary Endpoint: RSV -Positive MA-LRTIs within 360 Days After Birth
Maternal Vaccine Group (as Randomized)
RSVpreF 120 μg
(Na=3495)Placebo
(Na=3480)
Time Interval Number of Cases (%) Number of Cases (%) Vaccine Efficacyb(%) (99.17% CI)
210 Days after birth 70 (2.0) 127 (3.6) 44.9 (17.9, 63.5)
240 Days after birth 76 (2.2) 133 (3.8) 42.9 (16.1, 61.6)
270 Days after birth 82 (2.3) 137 (3.9) 40.1 (13.0, 59.2)
360 Days after birth 92 (2.6) 156 (4.5) 41.0 (16.2, 58.9)RSV-Positive MA -LRTIs Occurring Within 360 Days After Birth Met Statistical Criteria for Success
(CI LB>0%)
203Worldwide Research, Development and Medical
Vaccine Research and DevelopmentMaternal Vaccine Group (as Randomized)
RSVpreF 120 μg
(Na=3495)Placebo
(Na=3480)
Time Interval Number of Cases (%) Number of Cases (%) Vaccine Efficacyb(%) (99.17% CI)
90 Days after birth 10 (0.3) 31 (0.9) 67.7 (15.9, 89.5)
180 Days after birth 19 (0.5) 44 (1.3) 56.8 (10.1, 80.7)
360 Days after birth 38 (1.1) 57 (1.6) 33.3 (- 17.6, 62.9)
Abbreviations: EAC = endpoint adjudication committee; RSV = respiratory syncytial virus.
a. N = number of participants (at risk) in the specified group. These values are used as the denominators for the percentage calculations.
b. Vaccine efficacy was calculated as 1- (P/[1-P]), where P is the number of cases in the RSVpreF group divided by the total number of cases. The confidence interval was adjusted using Bonferroni procedure and accounting for the primary endpoints results.Secondary Endpoint: Hospitalizations Due to RSV within 360 Days
After Birth
Hospitalizations Due to RSV through 180 days Met Statistical Criteria for Success (CI LB>0%)
204Worldwide Research, Development and Medical
Vaccine Research and DevelopmentAbbreviations: EAC = endpoint adjudication committee; MA -RTI = medically attended respiratory tract illness; RSV = respiratory s yncytial virus.
a. N = number of participants (at risk) in the specified group. These values are used as the denominators for the percentage calculations.
b. Vaccine efficacy was calculated as 1- (P/[1- P]), where P is the number of cases in the RSVpreF group divided by the total number of cases.Exploratory Endpoint: RSV -Positive MA-RTIs (EAC confirmed) within
180 Days After Birth
Maternal Vaccine Group (as Randomized)
RSVpreF 120 μg
(Na=3495)Placebo
(Na=3480)
Time Interval Number of Cases (%) Number of Cases (%) Vaccine Efficacyb(%) (95% CI)
90 Days after birth 67 (1.9) 110 (3.2) 39.1 (16.7, 55.7)
180 Days after birth 157 (4.5) 253 (7.3) 37.9 (24.0, 49.5)RSV-Positive MA -RTIs through 180 Days After Birth
205Worldwide Research, Development and Medical
Vaccine Research and DevelopmentConsistent efficacy Was Observed Across RSV Subgroup A and B*
RSV Severe MA -LRTI
90, 180 Days
RSV MA -LRTI
90, 180 Days90 Days
180 Days
90 Days
180 DaysCase Split
(RSVpreF/Placebo) VE
6:33 81.8%
4:8 50.0%
2:25 92.0%
19:62 69.4%
7:14 50.0%
11:44 75.0%
Case Split
(RSVpreF/Placebo) VE
24:56 57.1%
8:12 33.3%
17:43 60.5%
57:117 51.3%
19:26 26.9%
38:87 56.3%Vaccine Efficacy (%) (95% CI)
Vaccine Efficacy (%) (95% CI)-100 -50 0 50 100RSV-BRSV-AOverallRSV-BRSV-AOverall

-100 -50 0 50 100RSV-BRSV-AOverallRSV-BRSV-AOverall
 * Exploratory Endpoint –no prespecified criterion for RSV A and B
206Worldwide Research, Development and Medical
Vaccine Research and DevelopmentRSVpreF Efficacious Against Severe Infant MA- LRTI in Phase 3 with a
Favorable Safety Profile
RSV = Respiratory Syncytial Virus; IA: Interim Analysis; MATISSE: MAT ernal Immunization Study for S afety and Efficacy; MA-LRTI: Medically Attended Lower Respiratory Tract Illness; CI: Confidence Interval;
DMC: Data Monitoring Committee; BLA: Biologics License Application; FDA: Food and Drug Administration
Source: Pfizer Press release, Oct 31, 2022Time Period Vaccine Efficacy
First 90 days of life* 81.8% (CI: 40.6%, 96.3%)
Six-month follow -up* 69.4% (CI: 44.3%, 84.1%)
Time Period Vaccine Efficacy
First 90 days of life* 57.1% (CI: 14.7%, 79.8%)
Six-month follow -up* 51.3% (CI: 29.4%, 66.8%)Primary Endpoint: Severe MA -LRTI
Primary Endpoint: MA -LRTI
RSVpreF investigational vaccine was well -tolerated with a favorable benefit -risk profile for the
maternal populations and their newborns.*Confidence intervals are 99.5% CI at 90 days and 97.58% CI at later intervals.
207Worldwide Research, Development and Medical
Vaccine Research and Development•The participants and their families
•The study investigators, nurses, coordinators, and laboratory personnel
•Pfizer essential colleagues and our vendorsThanks to

Summary: MedicalSafety and Efficacy of  Bivalent RSV Prefusion F Vaccine  in Vaccinated Mothers and their Infants Iona Munjal, MD Senior Director, Vaccine Research and Development   178Worldwide Research, Development and Medical Vaccine Research and DevelopmentBivalent RSV Prefusion F Vaccine  Proposed Indication: Prevention of lower respiratory  tract disease and severe lower  respiratory tract disease caused by  respiratory syncytial virus (RSV)DOSE LEVEL•120 µg without an adjuvant •Dose contains 60…


RSV Pediatric 07 Fleming Dutra 508

208
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Work Group considerations regarding maternal RSV
vaccine
Katherine Fleming -Dutra, MD FAAP
Co-lead, Maternal/Pediatric RSV Work
Group
ACIP General Meeting
February 23, 2023

209Should the Pfizer RSV bivalent prefusion F vaccine be recommended for
all pregnant people as a single dose given at 24 ‒36 weeks gestation?
This recommendation would be considered in the context of the current
standard of care for prevention of RSV disease in infants at the time of
ACIP vote. Policy question being considered by the work group
210Dosing window in the trial was 24 through 36 weeks gestation
Currently there are no data available on efficacy stratified by gestational age at time
of administration
Majority of infants in phase 3 trial were born ≥37 weeks gestation (94% in RSV
bivalent preF arm and 95% in placebo arm)
Most doses in the phase 3 trial were given at ≥28 weeks gestation
–25% doses given at ≥24 to <28 weeks
–30% doses given at ≥28 to <32 weeks
–45% doses given at ≥32 to <37 weeks
–0.1% doses given at ≥37 weeksKey considerations regarding RSV bivalent prefusion F
vaccine: timing of dose within pregnancy
Data provided by Pfizer
211All pregnant people in the trial received their first and only dose of RSV
vaccine
Currently there are no data available on
–Efficacy of the first lifetime dose during subsequent pregnancies
–Safety of additional doses given in subsequent pregnanciesKey considerations for RSV bivalent prefusion F vaccine:
number of total lifetime doses
212June 2023
–Summary of GRADE
–Cost effectiveness analysis
–EtR
October 2023
–ACIP vote (if product is licensed by this time)Proposed timeline of future ACIP presentations (tentative)
213

Summary: 208 Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Work Group considerations regarding maternal RSV  vaccine Katherine Fleming -Dutra, MD…


RSV Adults 01 Kotton 508

Centers for Disease Control and Prevention
Adult Respiratory Syncytial Virus (RSV) Session
Camille Kotton, MD
Chair, Adult RSV Work Group
Advisory Committee on Immunization Practices (ACIP)
February 23, 2023
2Adult RSV Work Group Membership
ACIP Voting Members
Camille Kotton (Chair)
Keipp Talbot
Sarah Long
Ex Officio Members
Rachel Zhang (FDA)
Judy Beeler (FDA)
Nicholas Geagan (FDA)
Nadine Peart (FDA)Sonnie Kim (NIH/NIAID)
Jeffrey Kelman (CMS)
Valerie Marshal (OIDP)CDC Lead
Michael Melgar
Consultants
Robert Atmar (Baylor College of Medicine)
Helen Chu (University of Washington)
Marie Griffin (Vanderbilt University Medical Center)Cynthia Lucero -Obusan (Veterans Health Administration)
Tracy Ruckwardt (NIH/NIAID)
Liaisons
Kenneth Schmader (AGS)
Shmuel Shoham (ACP)
Gretchen LaSalle (AAFP)April Killikelly (NACI, PHAC)Winnie Su (NACI, PHAC)Michael Hogue (APhA)Katherine Williams (APTR)Ruth Lynfield (NFID)Jennifer Heath (AIM)
3CDC Contributors
Coronavirus and Other Respiratory
Viruses Division
Fiona Havers
Meredith McMorrow
Diya SurieJennifer DeCuir
Lauren Roper
Mila PrillAmanda Payne
Natalie Thornburg
Melissa CoughlinJefferson Jones
Katherine Fleming-Dutra
Ismael Ortega SanchezImmunization Safety Office
Anne Hause
David Shay
Christine Olson
Immunization Services Division
Neil Murthy
Patricia Wodi
Debra Blog
Andrew LeidnerJamison Pike
4Recap of RSV session, October 2022
Manufacturer safety and efficacy presentation by GSK regarding
adjuvanted candidate RSV vaccine for older adults: RSVpreF3
Manufacturer safety and efficacy presentation by Pfizer regarding
bivalent candidate RSV vaccine for older adults: RSVpreF
Work group interim considerations regarding novel RSV vaccines for older adults
5Recent work group discussion
Cost effectiveness of RSV vaccination among U.S. older adults
GRADE and Evidence to Recommendations for GSK adjuvanted RSVpreF3
GRADE and Evidence to Recommendations for Pfizer bivalent RSVpreF
CDC vaccine safety surveillance systems
6Recent work group discussion
Possible policy recommendations* for RSV vaccination of U.S. older adults
–Should RSV vaccines be recommended for U.S. adults aged ≥65 years?
–Should RSV vaccines be recommended for U.S. adults aged ≥60 years?
*FDA has not yet completed review of safety and efficacy data for the GSK adjuvanted RSVpreF3 vaccine and the
Pfizer bivalent RSVpreF vaccine. ACIP recommendations would be made only if the vaccines are approved and
licensed by FDA.
7Agenda: Thursday February 23, 2023
Cost effectiveness of RSV vaccination
a
mong U.S. older adults
Comparison of RSV vaccination economic a
nalyses performed by U. Michigan/CDC,
GSK, and Pfizer
Evidence to Recommendations framework f
or GSK and Pfizer candidate vaccines
Discussion of vaccine policy optionsD
r. David Hutton
(U. Michigan)
Dr. Ismael Ortega Sanchez
(CDC)
Dr. Michael Melgar (CDC)
D r. Michael Melgar (CDC)

Summary: Centers for Disease Control and Prevention Adult Respiratory Syncytial Virus (RSV) Session Camille Kotton, MD Chair, Adult RSV Work Group Advisory Committee on Immunization Practices (ACIP) February 23, 2023 2Adult RSV Work Group Membership ACIP Voting Members Camille Kotton (Chair) Keipp Talbot Sarah Long Ex Officio Members Rachel Zhang (FDA) Judy Beeler (FDA) Nicholas Geagan (FDA) Nadine Peart (FDA)Sonnie Kim (NIH/NIAID) Jeffrey Kelman (CMS) Valerie Marshal (OIDP)CDC Lead Michael Melgar…


RSV Adults 02 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 Me rcon, MSCDC
•Michael Me lgar, MD
•Mila Prill , MSPH
•Jamison Pike, PhD
•Ismael Ortega - Sanchez, PhD
•Fiona Havers, MD
•Michael Whitaker, MPH
•Christopher Taylor, PhD
2
Conflicts of interest statements
–No known conflict of interests.
3
Methods: Study question
•Determine the cost -ef fectiveness of RSV vaccination by:
•Evaluating the population burden of disease in the US population
• ≥60 years old
• ≥65 years old
• ≥70 years old
• ≥75 years old
• Examining outcomes:
•resource utilization
•total cases
•total costs
•deaths
•quality -ad justed life years
•Comparing vaccination to no vaccination using the incremental cost -
ef
fectiveness ratio
•Scenario analyses exploring uncertainty.
•Perspective: Societal
4
Methods: Intervention(s)
•Target population: US adults, stratified by age
•Interventions: GSK and Pfizer vaccines
•Each compared to No Vaccination
•Base case assumes the age - based RSV vaccination recommendation is
for ages ≥65
•Time horizon: 1 year
•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
–
oRaw reported incidence may be underreported because of imperfect
PCR sensitivity
Base case assumption: 95% sensitivity
Additional scenario: lower sensitivity
Zhang et al study which found decreased RSV PCR sensitivity when paired serology
testing was added as an additional testing method.
7Zhang Y, Sakthivel SK, Bramley A, Jain S, Haynes A, Chappell JD, Hymas W, Lenny N, Patel A, Qi C, Ampofo K, Arnold SR, Self WH, Williams DJ, Hillyard D,
Anderson EJ, Grijalva CG, Zhu Y, Wunderink RG, Edwards KM, Pavia AT, McCullers JA, Erdman DD. Serology Enhances Molecular Diagnosis of Respiratory Virus
Infections Other than Influenza in Children and Adults Hospitalized with Community-Acquired Pneumonia. J Clin Microbiol . 2016 Dec 28;55(1):79-89. doi:
10.1128/JCM.01701-16. PMID: 27795341; PMCID: PMC5228265
Methods: Epidemiology
Hospitalization
Variable Value Range Source
60≤ age ≤64 years 42 29 –103
CDC R SVnet 65≤ age ≤74 years 67 48 –203
age ≥75 years 193 133 –575
•CDC RSVnet data from RSV seasons: 2015- 16, 2016- 17, 2017- 18, and 2018- 19.
•Base value is based upon the average burden adjusted rate over those four seasons.
•“burden adjusted” means it is adjusted for a "Standard" PCR test sensitivity of 95%*.
•Range lower bound is based on the lower 95% confidence limit for the base estimates
•Range upper bound is based on the upper 95% confidence limit but also uses a different
“burden adjustment” multiplier of 1.4x based on a reduced PCR test sensitivity **
* 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)-associated 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.
** Zhang Y , Sakthivel SK, Bramley A, Jain S, Haynes A, Chappell JD, Hymas W, Lenny N, Patel A, Qi C, Ampofo K, Arnold SR, Sel f WH, Williams DJ, Hillyard D, Anderson EJ,
Grijalva CG, Zhu Y , Wunderink RG, Edwards KM, Pavia AT, McCullers JA, Erdman DD. Serology Enhances Molecular Diagnosis of Respir atory Virus Infections Other than
Influenza in Children and Adults Hospitalized with Community -Acquired Pneumonia. J Clin Microbiol. 2016 Dec 28;55(1):79- 89. doi: 10.1128/JCM.01701 -16. PMID:
27795341; PMCID: PMC5228265.8RSV incidence, per 100,000
Hospitalization
Methods: Epidemiology
ED and Outpatient
Variable Value Range Source
RSV incidence, per 100,000
Emergency Department
60≤ age ≤64 years 74 59 –132
McLaughlin 202265≤ age ≤74 years 133 0 –478
age ≥75 years 133 0 –478
RSV Incidence, per 100,000Outpatient
60≤ age ≤64 years 1148 935 –2041
McLaughlin 2022 65≤ age ≤74 years 1519 1109 –2893
age ≥75 years 1519 1109 –2893
9•McLaughlin et. al. is a Pfizer- sponsored meta -analysis
•Range upper bound is based on the upper 95% confidence limit but also uses the authors’
multiplier of 1.5x to adjust for PCR sensitivity
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: Inputs
Variable Value Range Source
RSV mortality per hospitalization
60≤ age ≤64 years 3.9% 3.12% –4.68%
CDC RSVnet 65≤ age ≤74 years 4.3% 3.44% –5.16%
age ≥75 years 5.7% 4.56% –6.84%
10CDC RSVnet data includes the following RSV seasons: 2015 -16, 2016- 17, 2017- 18, and 2018- 19.
Ranges incorporate a 20% increase/reduction from the base case value
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
11
Methods: Efficacy
Variable Value Range Source
Vaccine Efficacy (%)
GSK
Medically attended RSV
LRTI/LRTD (ED, and
hospitalization)87.5% 58.4% –96.2% GSK phase 3 trial
Medically attended RSV ARI
(outpatient)79.0% 54.3% –91.5% GSK phase 3 trial
Pfizer
Medically attended RSV
LRTI/LRTD (ED, and
hospitalization)80.0% 6.3% –97.9% Pfizer phase 3 trial
Medically attended RSV ARI
(outpatient)69.2% 30.0% –88.0% Pfizer phase 3 trial
12
0%10%20%30%40%50%60%70%80%90%100%
0 2 4 6 8 10 12Efficacy
Month
Against RSV-associated ARI (outpatient) Est. Against RSV-associated ARI (outpatient)
Against hospitalization and ED Est. Against hospitalization and EDEfficacy: GSK
average 6-month
efficacy = trial efficacy
Exponential decay
13
0%10%20%30%40%50%60%70%80%90%100%
0 2 4 6 8 10 12Efficacy
Month
Against RSV-associated ARI (outpatient) Est. Against RSV-associated ARI (outpatient)
Against hospitalization and ED Est. Against hospitalization and EDEfficacy: Pfizer
average 6-month
efficacy = trial efficacy
Exponential decay
14
Methods: RSV Medical Costs
Variable Value Range Source
Disease -specific
hospitalization costs (per
hospitalization)
60≤ age ≤64 years $20,330 9,288 –45,454
Ackerson 2020* 65≤ age ≤74 years $20,330 10,491 –43,619
age ≥75 years $21,339 10,491 –43,619
Disease -specific ED costs
(per ED visit)
60≤ age ≤64 years $1,210 -
2016 Marketscan* 65≤ age ≤74 years $1,210 -
age ≥75 years $1,210 -
Disease -specific
outpatient costs (per outpatient visit)
60≤ age ≤64 years $117.58 65.88-145.38 MarketScan
and Medicare FFS, 2020-
202165≤ age ≤74 years $100.86 50.48-120.08
age ≥75 years $100.86 50.48-120.08
*Updated to Q3 2022$ using GDP Deflator15
Methods: Vaccination-Related Costs
Variable Value Range Source
Vaccine, per dose $100 $50-$200 Assumption
Vaccine administration $16.96 -HCPCS 90460 (Physician Fee
Schedule 2022)
16And productivity costs for individuals time at clinic or pharmacy
Methods: RSV Health-Related Quality-of -Life
Variable Value Range Source
QALYs lost due to
Outpatient RSV 0.0185 0.0053- 0.0347 JIVE COVID/RSV
utilities study
(unpublished) Hospitalized RSV 0.0193 0.0095- 0.0316
17
Methods: Additional Inputs
•Also included
–RSV illness productivity costs
–Vaccination productivity costs
–Vaccination adverse events
•Systemic reactions
•Injection site reactions
•Serious adverse events
•Medical costs
•Productivity costs
18
Methods: Sensitivity analyses
•Sensitivity analyses conducted
–One-W ay and Two-Way
–Age- b ased recommendation for RSV vaccination
•age ≥60 years
•age ≥65 years
•age ≥70 years
•age ≥75 years
–Vaccine cost
$50-$200
•Scenario analysis: Higher incidence
19
Results: Base Case
•Cohort of 100,000
•20% vaccination coverage
•Age-bas ed vaccination recommendation: ≥65 years
•$100 vaccine cost
•One Year Time Horizon
20
Health Outcomes
21$100 vaccine cost
One Year Time HorizonCohort:100,000, 20% uptakeAge-based vaccination recommendation: ≥65 years1519
133108
22 6649
651280
111 90
18 5540
541308
11493
19 5555
56
02004006008001000120014001600
No Vaccination GSK Pfizer
Number Needed to Vaccinate, GSK
22One Year Time Horizon
90
1,032
1,348
6,740
27,284
225
2,247 84
893
1,097
5,486
21,442
183
1,829 84
893
895
4,475
16,691
149
1,492 84
893
615
3,076
10,794
103
1,025
 - 5,000 10,000 15,000 20,000 25,000 30,000 35,000 40,000 45,000Number Needed to Vaccinate
age ≥60 years age ≥65 years age ≥70 years age ≥75 years
Number Needed to Vaccinate, Pfizer
23
One Year Time Horizon
103
1,200
1,567
7,835
31,717
261
2,612 95
1,038
1,275
6,377
24,927
213
2,126 95
1,038
1,040
5,202
19,404
173
1,734 95
1,038
715
3,576
12,548
119
1,192
 - 5,000 10,000 15,000 20,000 25,000 30,000 35,000 40,000 45,000Number Needed to Vaccinate
age ≥60 years age ≥65 years age ≥70 years age ≥75 years
Cost per Outcome Averted
($ thousands)
24$100 vaccine cost
One Year Time HorizonAge-based vaccination recommendation: ≥65 years$8 $83 $101 $507 $1,982
$17 $169
$9 $100 $123 $614 $2,402
$20 $205
 $- $500 $1,000 $1,500 $2,000 $2,500 $3,000Cost per Outcome Averted
ThousandsGSK Pfizer
Summary measure(s)
GSK
Costs (M) QALYs LostICER
($/QALY) LYs LostICER
($/LY)
No
Vaccination3.75 75 55
Vaccine 5.59 64 180,720 46 198,676
25QALY = Quality -Adjusted Life -Year
ICER = Incremental Cost -Effectiveness Ratio
LY = Life- Year
Cost, QALY, and LY Results per 100,000 (20% of whom are vaccinated)
Costs in Millions of 2022 dollarsICER values do not depend on cohort size or uptake$100 vaccine costOne Year Time Horizon Age-based vaccination recommendation: ≥65 years
Summary measure(s)
Pfizer
Costs (M) QALYs LostICER
($/QALY) LYs LostICER
($/LY)
No
Vaccination3.75 75 55
Vaccine 5.67 64 189,407 47 240,699
26QALY = Quality -Adjusted Life -Year
ICER = Incremental Cost -Effectiveness Ratio
LY = Life- Year
Cost, QALY, and LY Results per 100,000 (20% of whom are vaccinated)
Costs in Millions of 2022 dollarsICER values do not depend on cohort size or uptake$100 vaccine costOne Year Time Horizon Age-based vaccination recommendation: ≥65 years
Results: Sensitivity analyses,
•Tornado Diagrams
–one parameter varied at a time
•Age and Vaccine Cost
•Higher Incidence / Lower PCR Sensitivity
27
Sensitivity analyses, GSK Tornado Diagram
28$100 vaccine cost
One Year Time HorizonAge-based vaccination recommendation: ≥65 years$0 $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000
Vaccine Cost
Incidence of RSV hospitalization
Outpatient QALYs Lost
GSK Vaccine Effectiveness LRTD
Incidence of outpatient visits for RSV
Cost per Hospitalization
Mortality, adults hospitalized with RSV
GSK Vaccine Effectiveness ARI
ED Incidence
QALYs lost Injection Site ReactionICER ($/QALY)Age ≥65
Low Assumption High Assumption
Sensitivity analyses, Pfizer Tornado
Diagram
29$100 vaccine cost
One Year Time HorizonAge-based vaccination recommendation: ≥65 years
* A
t low Pfizer vaccine efficacy, the ICER rises to $574,730/QALY574,730$0 $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000
Pfizer Vaccine Effectiveness LRTD
Vaccine Cost
Incidence of RSV hospitalization
Outpatient QALYs Lost
Pfizer Vaccine Effectiveness ARI
Incidence of outpatient visits for RSV
Mortality, adults hospitalized with RSV
Cost per Hospitalization
ED Incidence
Probability of Serious Adverse EventICER ($/QALY)Age ≥65
Low Assumption High Assumption
Sensitivity analysis: Vaccine Cost, GSK
30One Year Time Horizon $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000 $500,000
 $50  $75  $100  $125  $150  $175  $200ICER ($/QALY)
Vaccine Cost
age ≥60 years age ≥65 years age ≥70 years age ≥75 years
Sensitivity analysis: Vaccine Cost, Pfizer
31One Year Time Horizon $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000 $500,000
 $50  $75  $100  $125  $150  $175  $200ICER ($/QALY)
Vaccine Cost
age ≥60 years age ≥65 years age ≥70 years age ≥75 years
Sensitivity analyses, Higher Incidence
32•Higher incidence in the next 2 slides
assumes that RT -PCR test sensitivity is
lower than 95% and that additional RSV testing modalities would detect more cases at every level of care
1,2
1For incidence of hospitalization (RSV -NET), in lieu of adjusting observed incidence for RT -PCR sensitivity of 95%, a
1.4x multiplier is implemented based on Zhang et al. 2016 .
Zhang Y, et al. Serology Enhances Molecular Diagnosis of Respiratory Virus Infections Other than Influenza in Children and Ad ults Hospitalized with
Community -Acquired Pneumonia. J Clin Microbiol . 2016 Dec 28;55(1):79 -89. doi: 10.1128/JCM.01701- 16. PMID: 27795341; PMCID: PMC5228265.
2For incidence of outpatient and ED visits (McLaughlin et al. 2022), this applies the authors’ multiplier of 1.5x to the
lower (base case) 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.
Sensitivity analyses, GSK
Higher Incidence
33Age-based vaccination recommendation: ≥65 years
One Year Time Horizon $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000
 $
50  $75  $100  $125  $150  $175  $200ICER ($/QALY)
Vaccine Cost
GSK Base age ≥65 years GSK Higher Incidence age ≥65 years
Sensitivity analyses, Pfizer Higher Incidence
34Age-based vaccination recommendation: ≥65 years
One Year Time Horizon $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000
 $50  $75  $100  $125  $150  $175  $200ICER ($/QALY)
Vaccine Cost
Pfizer Base age ≥65 years Pfizer Higher Incidence age ≥65 years
Limitations
•Model Structure
–No risk groups
–No dynamic transmission. No impact of the vaccine on transmission and
in
direct effects
–No direct medical costs post-di scharge (e.g. rehab)
•Uncertain inputs
–Vaccine cost
–RSV Incidence
–Long-t erm efficacy
35
Summary
•Results vary based on:
–Vaccine Cost
•ICER: ~80,000 -3 85,000 $/QALY
–Vaccine Efficacy
•ICER: ~150,000 -5 75,000 $/QALY
–Ages Vaccinated
•ICER: ~100,000 -2 30,000 $/QALY
–Incidence of Hospitalization
•ICER: ~30,000 -2 50,000 $/QALY
36
Thank You
•Please send comments to:
•dwhutton@umich.edu
37

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 Me rcon, MSCDC •Michael Me lgar, MD •Mila Prill , MSPH •Jamison…


RSV Adults 03 Ortega Sanchez 508

Economics of Vaccinating U.S. Adults ≥60
years-old  against
Respiratory Syncytial Virus
A SUMMARY REPORT COMPARING MODELS FROM:
GSK,Pfizer AND University of Michigan -CDC
Ismael R. Ortega -Sanchez, PhD
NCIRD/CDC
ACIP Meeting, February 23, 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 author list and affiliations, upon request ]
•All authors: No conflicts of interest
2
Economic analysis
Policy questions: Should adults ≥60 years of age (or ≥65 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
Unvaccinated
≥65yr -olds
(or ≥60yr -olds)Intervention
Vaccinating≥65yr -olds
(or ≥60yr -olds)
B
ase-case scenario: What is the incremental cost -effectiveness of vaccinating adults aged
≥65 years (or ≥60 years) using RSV vaccine relative to “No vaccination”?
3
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
4
5Modeling design and assumptions
GSK Pfizer UM-CDC
Static analytical decision-making models ✔ ✔ ✔
Sensitivity analyses (and probabilistic simulation)✔(✔)✔(✔)✔
Hypothe tical popul ation ≥65yrs-old (and ≥60-yrs-old)✔(✔)✔(✔)✔(✔)
Time Frame: at least 1 yr. after a dose of RSV vaccine✔ ✔ ✔
Analytic Horizon: Age-specific Life Expectancy✔ ✔ ✔
Discount rate: 3% ✔ ✔ ✔
Year of econom ic 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 Pfizer UM-CDC
✔ ✔ ✔
✔ ✔ ✔
✔ ✔ ✔
✔ ✔ ✔
✔ ✔ ✔
✔ ✔ ✔
✔ ✔ ✔
✔ ✔ ✔
HCRU = health care resource use
UMich -CDC: Scenario analysis for age group,
$100 vaccine cost and vaccine candidate
7$230
$181
$155
$104 $234
$189
$166
$117
 $- $50 $100 $150 $200 $250
age ≥60 years age ≥65 years age ≥70 years age ≥75 years Incremental Cost per QALY saved
Thousands
Age Group VaccinatedGSK Pfizer
GSK, Pfizer and UM-CDC models comparison:
Selected outcome ratios for RSV vaccines
8UM-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
UM-CDC model : One-way Sensitivity Analyses
Base case: Age ≥65yrs $180,720/QALY (GSK), $189,407/QALY (Pfizer)
9One Year Time Horizon
*
At lower bound of Pfizer vaccine efficacy (VE =6.3%), the ICER rises to >$574 Thousand /QALY$0 $100 $200 $300 $400
Vaccine Cost
Incidence of RSV hospitalization
Outpatient QALYs Lost
GSK Vaccine Effectiveness LRTD
Incidence of outpatient visits for RSV
Cost per Hospitalization
Mortality, adults hospitalized with RSV
GSK Vaccine Effectiveness ARI
ED Incidence
QALYs lost Injection Site ReactionGSK: $/QALY saved ( in thousands )
Low Assumption High Assumption$0 $100 $200 $300 $400
Pfizer Vaccine Effectiveness LRTD
Vaccine Cost
Incidence of RSV hospitalization
Outpatient QALYs Lost
Pfizer Vaccine Effectiveness ARI
Incidence of outpatient visits for RSV
Mortality, adults hospitalized with RSV
Cost per Hospitalization
ED Incidence
Probability of Serious Adverse EventPfizer:  $/QALY ( in thousands )
Low Assumption High Assumption*
GSK model : One-way Sensitivity Analyses
Base case: Age ≥60 years; $ 78,971 /QALY saved
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 <24 months
Probability of death given RSV LRTD
Proportion RSV LRTD within first RSV ARI event
Vaccination costs per administered dose with RSVPreF3 vaccine -Purchase cost per dose – Cost
RSVPreF3 vaccine: Peak % efficacy after first vaccination against RSV LRTD caused by first RSV
infection
Baseline QALYs -General population
Efficacy against RSV ARI: Waning rates first vaccination with RSVPreF3 vaccine <24 months
Probability of AE 'Grade 3 ' after first or revaccination with RSVPreF3 vaccine
10
Pfizer model : One-way Sensitivity Analyses
Base case: Age≥60 years: $50,104/QALY saved
11
Base case

GSK, Pfizer and UM-CDC models comparison:
Selected inputs
12•RSV-hospitalization rate
GSK: Proportion of MA 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)
•Unitary medical cost of RSV outcomes
•GSK: Age -& outcome specific cost for symptomatic RSV LRTD & URTI cases (MA and non -MA) (CMS)
•Pfizer: Age-, outcome- & comorbidity -specific cost for MA RSV
•CDC: Age -& outcome -specific cost for MA RSV
•Initial VE & waning over time
GSK: Phase 3, monthly waning: ARI (5.36%), LRTD (2.63%) until 12mos, then to 0%
Pfizer: Phase 3, flat 7mos, then linear decay to 0% at 24mos
CDC: GSK’s & Pfizer’s phase 3, flat 6mos, exponential decay until 12mos, then to 0%
MA = medically attended, ARI = acute respiratory infection
13UM-CDC GSK Pfizer
Incidence of RSV outpatient
illness (per 100,000 persons per year)1,519
(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)108
(base- case for adults ≥65 years)d256
(for adults ≥65 years)b,e300
(base- case for adults
≥65 years)c
Direct medical costs per RSV hospitalization$20,330 –$21,339
(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 ; unadjusted for under -detection of RT -PCR testing
b Adapted from Belongia et al. Open Forum Infect Dis (2018): https://doi.org/10.1093/ofid/ofy316
c McLaughlin et al. Open Forum Infect Dis (2022): https://doi.org/10.1093/ofid/ofac300 ; Ramirez et al. (under review)
d RSV -NET, CDC unpublished data
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): https://doi.org/10.1093/infdis/jiaa183
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
GSK model : Sensitivity of Cost per QALY saved to RSV -
Related Hospitalization Rates among Adults ≥60 years
14S8: Branche et al. (2022b; high BoD
season [New York City, 2018 -2019]);
S9: Branche et al. (2022b; low BoD
season [Rochester, 2019 -2020]);
S10: Zheng et al. (2022; low SES);
S11: Zheng et al. (2022; medium SES); S12: Zheng et al. (2022; high SES); S13: McLaughlin et al. (2022;
unadjusted);
S14: McLaughlin et al. (2022; adjusted);
S15: Widmer et al. (2012);
S16: Herring et al. (2022; Belongia et al.
[2018] estimate); S17: Herring et al. (2022; Falsey et al.
[2005] estimate); S18: DeMartino et al. (2022);
S19: Fust et al. (2022a and 2022b).
Note: BoD = burden of disease; SES = socioeconomic status.
* Derived from GSK modeling results.

S3:
S6:
S1:
S7:S5:
S4:
S2:
Base- casePfizer model : Sensitivity of Cost per QALY saved to RSV -
Related Hospitalization Rates among Adults ≥60 years
15• S1: Pooled unadjusted rates from
McLaughlin et al. (active prospective
surveillance studies only)1
• S2: Based on pooled adjusted rates from
McLaughlin et al. 1.5 -fold (active
prospective surveillance studies only)1
• S3: Rates in Rochester, NY , averaged
across all study years, from Branche et al.2
• S4: Rates in New York, NY , averaged
across all study years, from Branche et al.2
• S5: Rates averaged across all study years
and accounting for the proportion of RSV-
confirmed cases treated in hospital from
Belongia et al.3
• S6: Rates based on Matias et al.4
• S7: Rates based on Widmer et al.5
Base Case : Ongoing unvetted prospective
study with adjusted RSV detection rates of 1.6-to 1.7-fold. Pfizer Inc. data on file 1. McLaughlin JM, et al. Open Forum Infectious Diseases . 9(7), 2022
2. Branche AR et al. Clinical Infectious Diseases. 2021;74(6):1004- 1011.
3. Belongia et al. Open Forum Infect Dis . 2018;5(12):ofy316.
4. Matias et al. BMC Public Health. 2017;17(1):271.
5. Widmer et al. Influenza and Other Respiratory Viruses . 2014;8(3):347-352.
UM-CDC model : Sensitivity of Cost per QALY saved to RSV -
Related Hospitalization Rates among Adults ≥65 years
16Base case: mean value of the burden adjusted rate over RSV seasons: 2015 -16, 2016- 17, 2017- 18, and 2018- 19. Adjusted rate for 95% sensiti vity of PCR testing. CDC RSVnet
Lower bound: mean of  lower confidence limit estimates across all 4 seasons assuming 95% sensitivity of PCR testing.
Upper bound: mean of upper confidence limit estimates across all 4 seasons assuming 71% sensitivity of PCR testing.$180,720 $189,407
 $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000
0 50 100 150 200 250 300 350Incremental Cost per QALY saved
Incidence of RSV Hospitalization per 100,000 persons per yearGSK
Pfizer
Incidence Range
Minimum
Base Case
Higher Incidence
Scenario
GSK, Pfizer and UM-CDC:  Initial or Early Peak
of Vaccine Efficacy
17a VE over mean 6 –7 months of 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; IDWeek abstract ; VE against acute respiratory illness, regardless of whether medically attended
d Manufacturer phase 3 trial data; GSK: VE against medically attended lower respiratory tract disease; Pfizer: VE against medica lly attended lower respiratory tract illness with ≥3 lower
respiratory symptomse Manufacturer phase 3 trial data; GSK: IDWeek abstract
VE against lower respiratory tract disease, regardless of whether medically attended; Pfizer: IDWeek abstract VE against lower
respiratory tract illness with ≥3 lower respiratory symptoms, regardless of whether medically attended (95% CI applied)UM-CDC GSK Pfizer
GSK vaccine Pfizer vaccine
Vaccine efficacy (VE) against RSV
outpatient illnessa79.0
(54.3– 91.5)b69.2
(30.0– 88.0)b71.7
(56.7– 82.3)c69.2
(30.0– 88.0)b
VE against RSV hospitalization and emergency department visit
a87.5
(58.4– 96.2)d80.0
(6.3– 97.9)d82.6
(57.9– 94.1)e85.7
(37.9– 98.4)e
GSK, Pfizer and UM-CDC: Assumption on
waning of vaccine efficacy (VE) per outcome
18GSKVE 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 monthsResidual 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

Pfizer : Impact of vaccine’s duration of protection
(DoP) assumption on ≥65yrs Cost per QALY saved
19
Base- Case
Base- Case*
* RSV hospitalization incidence labelled “CDC x1.4” used data presented by CDC at IDWeek 2022 (Havers et al. https://doi.org/10.1093/ofid/ofac492.1828 ),
upwardly adjusted by a factor of 1.4 (based on Zhang et al. https://doi.org/10.1128/jcm.01701 -16).
Comparison of GSK and Pfizer vaccines: base case &
scenario $/QALY results using UM-CDC model
20aRecommendation = vaccination at age ≥65 years; vaccine unit cost = $100; incidence rates of RSV outcomes unadjusted for incre ased diagnostic yield from testing
in addition to RT -PCR on a respiratory specimen; vaccine efficacy only considered for one year post -vaccination
b Base case incidence rates adjusted upward for increased diagnostic yield from testing in addition to RT -PCR on a respiratory s pecimen (1.5x for outpatient illness
[McLaughlin et al; Open Forum Infect Dis (2022)], 1.4x for inpatient illness [Zhang et al; J Clin Microbiol (2016)])Scenario GSK Pfizer
Vaccine cost $200 per dose (one year time frame) $374,530 $384,267
Vaccinating adults aged ≥60 years $229,895 $233,779
Medical cost for hospitalization (lower bound) $199,018 $205,236
Base case a (Vaccine Price $100, 1 year time frame) $180,720 $189,407
Higher incidence of RSV b $91,028 $104,160
Vaccine cost $50 per dose (one year time frame) $85,815 $91,977
Limitations
21•Factors not considered that may result in overestimating the ICER
(underestimating the cost -effectiveness) of RSV vaccination
•None of the 3 models included RSV- related medical costs incurred after
discharge from an RSV- associated hospitalization or emergency department
visit:
•Stay in long-term care or rehabilitation facility
•Assisted living at home
•Productivity losses incurred by caregivers whose support is needed post-discharge
•All of the 3 models assumed no indirect effects of vaccination (i.e., no protection against RSV transmission)
•Vaccine efficacy beyond clinical trial follow -up time (6 –7 months) is unknown
•All 3 models assumed non- zero declining efficacy beyond 6– 7 months
(UM-CDC : 12 months, GSK: 12 months, Pfizer : 24 months ).
Conclusion
22•Differences in key inputs among GSK, Pfizer and UM-CDC models explain differences in results:
•Incidence of hospitalization
•Duration of vaccine efficacy
•Medical costs
•Vaccine costs
•Assumptions and selection of input data were crucial in differences in ICERs
•Adjustment approach of incidence rates of Hospitalization, ER and Outpatient
•Selection of medical costs sources and data extraction approach
•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
•Meredith McMorrow
A
lso:
•Adult RSV working group members
•Econ Team members at ISD/NCIRD
23

End of Summary

Summary: Economics of Vaccinating U.S. Adults ≥60  years-old  against  Respiratory Syncytial Virus A SUMMARY REPORT COMPARING MODELS FROM: GSK,Pfizer AND University of Michigan -CDC Ismael R. Ortega -Sanchez, PhD NCIRD/CDC ACIP Meeting, February 23, 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…