03 RSV Mat Ped Fleming Dutra 508

Centers for Disease Control and Prevention
Evidence to Recommendations Framework:
Pfizer Maternal RSVpreF Vaccine
Katherine Fleming -Dutra, MD
Co-Lead, Respiratory Syncytial Virus Vaccines -Pediatric/Maternal Work Group
Coronavirus and Other Respiratory Viruses Division
National Center for Immunization and Respiratory Diseases
June 22, 2023
2Evidence to Recommendations (EtR) Framework
Policy Question
▪Should vaccination with Pfizer RSVPreF vaccine (120µg antigen, 1 dose
IM given 24 –36 weeks gestation) be recommended for pregnant people
to prevent RSV disease in infants?
RSVpreF is a bivalent recombinant stabilized prefusion F protein subunit vaccine
3Evidence to Recommendations (EtR) Framework
PICO Question
▪Population Pregnant people 24 –36 weeks gestation
Intervention Pfizer RSVPreF Vaccine
Comparison No vaccine
Outcomes▪Medically attended RSV -associated lower respiratory tract infection in infants
▪Hospitalization for RSV -associated lower respiratory tract infection in infants
▪Intensive care unit (ICU) admission from RSV hospitalization in infants
▪Mechanical ventilation from RSV hospitalization in infants
▪RSV-associated death in infants
▪All-cause hospitalization for lower respiratory tract infection in infants
▪All-cause medically attended lower respiratory tract infection in infants
▪Serious adverse events in pregnant people
▪Reactogenicity (grade 3+) in pregnant people
▪Serious adverse events in infants
▪Preterm birth
4Evidence to Recommendations (EtR) Framework
EtR Domain Question(s)
Public Health Problem ▪Is the problem of public health importance?
Benefits and Harms ▪How substantial are the desirable anticipated effects?
▪How substantial are the undesirable anticipated effects?
▪Do the desirable effects outweigh the undesirable effects?
Values ▪Does the target population feel the desirable effects are large relative
to the undesirable effects?
▪Is there important variability in how patients value the outcome?
Acceptability ▪Is the intervention acceptable to key stakeholders?
Feasibility ▪Is the intervention feasible to implement?
Resource Use ▪Is the intervention a reasonable and efficient allocation of resources?
Equity ▪What would be in the impact of the intervention on health equity?
EtRDomain: Public Health Problem
Is the problem of public health importance?
6RSV is the leading cause of hospitalization in U.S.
infants1
▪Most (68%) infants are infected in the first year of life
and nearly all (97%) by age 2 years2
▪2-3% of young infants will be hospitalized for RSV3,4,5
▪RSV is a common cause of lower respiratory tract
infection in infants
▪Highest RSV hospitalization rates occur in first months
of life and risk declines with increasing age in early
childhood3,5
▪79% of children hospitalized with RSV aged <2 years
had no underlying medical conditions3
1Suh et al. JID 2022 . 2Glezen et al, Arch Dis Child, 1986 ; 3Hall et al, Pediatrics, 2013 ; 4Langley & Anderson, PIDJ, 2011 ; 5CDC NVSN data
Image: Goncalves et al. Critical Care
Research and Practice 2012
7Seasonality of RSV transmission —National Respiratory
and Enteric Virus Surveillance System, NREVSS1, 2017 –
2020
0510152025
27293133353739414345474951 135791113151719212325
Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun% PCR results RSV -positive
Epidemiologic week
Abbreviation : PCR = polymerase chain reaction; RSV = respiratory syncytial virus. 1. https://www.cdc.gov/mmwr/volumes/72/wr/mm7214a1.htm
* 3-week centered moving averages of percentage of RSV -positive PCR results nationwide. The black dotted line represents the thr eshold for a seasonal epidemic (3% RSV -positive laboratory PCR results).
8Changes in seasonality of RSV transmission following
SARS -CoV2 introduction —NREVSS1, 2017 –2023
0510152025
27293133353739414345474951 135791113151719212325
Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun% PCR results RSV -positive
Epidemiologic week2017 –18 2018 –19 2019 –20 2020 –21 2021 –22 2022 –23
Abbreviation : PCR = polymerase chain reaction; RSV = respiratory syncytial virus. 1. https://www.cdc.gov/mmwr/volumes/72/wr/mm7214a1.htm
* 3-week centered moving averages of percentage of RSV -positive PCR results nationwide. The black dotted line represents the thr eshold for a seasonal epidemic (3% RSV -positive laboratory PCR results).
9Public Health Problem -Work Group Interpretation
▪Is RSV among infants of public health importance?
NoProbably
NoProbably
YesYes VariesDon’t
know
EtRDomain: Benefits and Harms
How substantial are the desirable anticipated effects?
How substantial are the undesirable anticipated effects?
Do the desirable effects outweigh the undesirable effects?
11GRADE Outcomes, Importance, and Data Sources:
Pfizer maternal RSVpreF vaccine
Outcome Importance1 Data sources
Benefits
Medically attended RSV -associated lower respiratory tract infection in infants Critical Phase 3 RCT
Hospitalization for RSV -associated lower respiratory tract infection in infants Critical Phase 3 RCT
ICU admission from RSV hospitalization in infants Important No data
Mechanical ventilation from RSV hospitalization in infants Important No data
RSV-associated death in infants Important Phase 3 and phase 2b2RCT
All-cause medically attended lower respiratory tract infection in infants Important Phase 3 RCT
All-cause hospitalization for lower respiratory tract infection in infants Important No data
Harms
Serious adverse events in pregnant people Critical Phase 3 and phase 2b2RCT
Reactogenicity (grade 3+) in pregnant people Important Phase 3 and phase 2b2RCT
Serious adverse events in infants Critical Phase 3 and phase 2b2RCT
Preterm birth (<37 weeks) Critical Phase 3 and phase 2b2RCT
RCT = Randomized -controlled trial
1 Three options: Critical; Important but not critical; Not important for decision making
2 Among phase 2b trial participants, only those who received the vaccine formulation of the phase 3 trial were included
12Efficacy estimates and concerns in certainty of
assessment, benefits : Pfizer maternal RSVpreF vaccine
Outcome Importance1 Data sources Manufacturer
calculated vaccine
efficacy (97.58% or
99.17% CI)2Concerns in certainty
assessment
Benefits
Medically attended RSV -associated lower respiratory tract infection in
infants (0 –180 days)Critical Phase 3 RCT 51.3% (29.4, 66.8) None
Hospitalization for RSV -associated lower respiratory tract infection in
infants (0 –180 days)Critical Phase 3 RCT 56.8% (10.1, 80.7) Imprecision (serious)3
ICU admission from RSV hospitalization in infants Important No data
Mechanical ventilation from RSV hospitalization in infants Important No data
RSV-associated death in infants Important Phase 3 and phase 2b4
RCT1 RSV -associated death occurred in the placebo arm of the
phase 3 trial that was recorded at day 120 after birth. No
RSV-associated deaths were recorded in the phase 2b trial.
All-cause medically attended lower respiratory tract infection in
infants (0 –180 days)Important Phase 3 RCT 2.5% ( -17.9, 19.4) Imprecision (serious)3
All-cause hospitalization for lower respiratory tract infection in infants Important No data
RCT = Randomized -controlled trial
1 Three options: Critical; Important but not critical; Not important for decision making
2 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 the Bonferroni procedure and accounting for the primary endpoints results. 97.58% confidence interval used for medically attended RSV -associated lower
respiratory tract infection in infants, 99.17% confidence interval used for other endpoints.
3 Serious concern for imprecision due to the width of the confidence interval containing estimates for which different policy decisions might be considered
4  Among phase 2b trial participants, only those who received the vaccine formulation of the phase 3 trial were included
13Efficacy estimates and concerns in certainty of
assessment, harms : Pfizer maternal RSVpreF vaccine
Outcome Importance1Data sources Relative Risk2 (95%
confidence interval)Concerns in certainty
assessment
Harms
Serious adverse events in pregnant people Critical Phase 3 and
phase 2b2RCT1.06 (0.95, 1.17) Imprecision (serious)3
Reactogenicity (grade 3+) in pregnant people Important Phase 3 and
phase 2b2RCT0.97 (0.72, 1.31) Indirectness (serious)4
Serious adverse events in infants Critical Phase 3 and
phase 2b2RCT1.01 (0.91, 1.11) Imprecision (serious)3
Preterm birth (<37 weeks) Critical Phase 3 and
phase 2b2RCT1.20 (0.99, 1.46) Imprecision (very serious)5
RCT = Randomized -controlled trial
1 Three options: Critical; Important but not critical; Not important for decision making
2 Pooled relative risk estimates were independently calculated using counts of events and participants in the phase 3 trial i nterim analysis, and phase 2b trial among those
who received the phase 3 vaccine formulation
3 Serious concern for imprecision due to the width of the confidence interval containing estimates for which different policy decisions might be considered
4 Serious concern for indirectness as these data only includes systemic reactions
5 Very serious concern for imprecision due to the width of the confidence interval containing estimates for which different p olicy decisions might be considered and not
meeting optimal information size requirements
14Summary of GRADE: Pfizer maternal RSVpreF vaccine
Outcome Importance Design (# of
studies)Findings Evidence Type
Benefits
Medically attended RSV -associated lower respiratory
infection in infants Critical RCT (1) Pfizer RSVPreF maternal vaccine is effective in preventing medically
attended RSV -associated lower respiratory infection in infants High
Hospitalization for RSV -associated lower respiratory
tract infection in infants Critical RCT (1) Pfizer RSVPreF maternal vaccine may be effective in preventing
hospitalization for RSV -associated lower respiratory tract infection in
infants Moderate
ICU admission from RSV hospitalization in infants Important No data Not evaluated
Mechanical ventilation from RSV hospitalization in
infants Important No data Not evaluated
RSV-associated death in infants Important RCT (2) 1 event observed in a placebo recipient among both trials Not evaluated
All-cause medically attended lower respiratory tract
infection in infants Important RCT (1) Pfizer RSVPreF maternal vaccine is not effective in preventing all -cause
medically attended lower respiratory tract infection in infants Moderate
All-cause hospitalization for lower respiratory tract
infection in infants Important No data Not evaluated
Harms
Serious adverse events in pregnant people Critical RCT (2) SAEs in pregnant people were balanced between vaccine and placebo
groupsModerate
Reactogenicity (grade 3+) in pregnant people Important RCT (2) Reactogenicity in pregnant people was balanced between vaccine and
placebo groupsModerate
Serious adverse events in infants Critical RCT (2) SAEs in infants were balanced between vaccine and placebo groups Moderate
Preterm birth (<37 weeks) Critical RCT (2) Preterm births were unbalanced between vaccine and placebo groups Low
15Summary of GRADE: Pfizer maternal RSVpreF vaccine
15Overall
evidence type:
Low

16Outcome: Preterm births (n=2 studies), Pfizer maternal
RSVpreF vaccine
16Publication Definition Events/Vaccine
(n/N)Events/Placebo
(n/N)Relative Risk (95% CI)
Phase 3<34 weeks 21/3568 12/3558 1.75 (0.86, 3.54)
<37 weeks 201*/3568 169/3558 1.19 (0.97, 1.45)
Phase 2b<34 weeks 0/115 1/117 0.34 (0.01, 8.24)
<37 weeks 6/115 3/117 2.03 (0.52, 7.94)
*When reported as an adverse event of special interest, 202 preterm births occurred in the vaccine arm; the relative risk is minimally changed at 1.19 (0.98, 1.45) when using this count
17Outcome: Preterm births (n=2 studies), Pfizer maternal
RSVpreF vaccine
▪Measures of effect
–Relative risk: 1.20 (0.99, 1.46)
–Absolute risk*:  9 more per 1,000 (from 0 fewer to 22 more)
▪Concerns in certainty assessment:
–Very se rious concern for imprecision due to the width of the
confidence interval containing estimates for which different policy
decisions might be considered and not meeting optimal information
size requirements
▪Evidence type: Low
*Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up. Abso lute risk estimates should be
interpreted in this context.
18Preterm birth rates in maternal RSV vaccine clinical
trials: GSK
▪Trial of a similar GSK maternal RSV vaccine (stabilized prefusion F protein vaccine
without an adjuvant) was halted due to an imbalance of preterm births
▪Imbalance of neonatal deaths was a consequence of preterm birth imbalance
▪Imbalance in preterm births was seen in low and middle -income countries (RR: 1.57,
95% CI: 1.17, 2.10) but not high -income countries (RR: 1.04, 95% CI: 0.68, 1.58)
▪Imbalance was observed from April -December 2021, but not consistently after
December 2021
▪Reason for the imbalance remains unclear
Study vaccine given at 240/7to 340/7weeks gestation
Vaccines and Related Biological Products Advisory Committee February 28 -March 1, 2023 Meeting Briefing Document -Sponsor GSK ( fda.gov)Outcome Vaccine group, n (%)
N=3,496Placebo group, n (%)
N=1,739Relative Risk
(95% CI)
Preterm birth <37 weeks 238 (6.81%) 86 (4.95) 1.38 (1.08, 1.75)
Neonatal death 13 (0.37%) 3 (0.17%) 2.16 (0.62, 7.55)
19Preterm birth rates in maternal RSV vaccine clinical
trials: Novavax
▪Phase 3 clinical trial in 4,636 women randomized 2:1, vaccine to placebo
▪Vaccine formulation: 120μg of recombinant RSV F protein nanoparticle vaccine
adsorbed to 0.4mg of aluminum (Novavax vaccine was not stabilized in the
prefusion form)
▪Maternal vaccine did not reach primary efficacy endpoints and thus did not move
forward, but there were no safety concerns (preterm births or other) in this trial
Preterm Birth Definition Preterm Birth in Vaccine group,
n (%)
N=2,986Preterm Birth in Placebo,
n (%)
N=1,554
<37 weeks among infants* 175 (5.9%) 96 (6.2%)
*Study vaccine given at ≥28 through 36 weeks and 0 days gestation. Data from Table 1 among infants for whom the protocol -mandated dating ultrasonography result was
available for calculating gestational age.
1. Madhi SA, Polack FP , Piedra PA, et al. Respiratory syncytial virus vaccination during pregnancy and effects in infants. N Engl J Med 2020;383:426 -39. DOI:
10.1056/NEJMoa1908380
20Preterm birth and low birth weight outcomes in
maternal RSV vaccine clinical trials: Pfizer RSVpreF
vaccine phase 3 trial data
*Confidence intervals not reported for these estimates.
Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Presentation -Review of Efficacy and Safety of Respiratory Syncytial Virus Vaccine (ABRYSVO)
(fda.gov)RSVpreF vaccine group
N=3,568Placebo group
N=3,558
Preterm birth (<37 weeks) 5.7% (95% CI: 4.9%, 6.5%) 4.7% (95% CI: 4.1%, 5.5%)
Late preterm birth (≥34 to
<37 weeks)5.0%* 4.4%*
Low birth weight ( ≤2500g) 5.1% (95% CI: 4.4%, 5.8%) 4.4% (95% CI: 3.7%, 5.0%)
21Infant deaths in maternal RSV vaccine clinical trials:
Pfizer RSVpreF vaccine phase 3 trial data
▪Infant deaths (all -cause) through 24 months of age: 5 (0.1%) in the
RSVpreF group vs 12 (0.3%) in placebo group
▪Among infant deaths in the RSVpreF group
–4 of 5 deaths were considered unrelated to the investigational product
by FDA
–1 death was in an infant with extreme prematurity (27 weeks) and
prematurity -related complications, and FDA was unable to exclude
possibility of relationship to investigational product
Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Presentation -Review of Efficacy and Safety of Respiratory Syncytial Virus Vaccine (ABRYSVO)
(fda.gov)
22
Time from Vaccination to Birth Among Preterm and
Term Births, Infant Participants, Safety Population:
Pfizer RSVpreF vaccine phase 3 trial data
▪Median gestational age at vaccination in trial was 31 weeks
Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Presentation -Review of Efficacy and Safety of Respiratory Syncytial Virus Vaccine (ABRYSVO)
(fda.gov)
23Subgroup analysis of gestational age at birth among
live births by country income level : Pfizer RSVpreF
vaccine phase 3 trial data
▪In high -income countries, preterm birth rate was 5.1% (126/2494) in
RSVpreF recipients vs 5.1% (126/2484) placebo recipients
▪Imbalance was most prominent in upper middle income countries: 7.5%
(72/964) in RSVpreF recipients vs. 4.1% (39/961) in placebo recipients
Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDA
24
Subgroup analysis of gestational age at birth among
live births, South Africa and US: Pfizer RSVpreF vaccine
phase 3 trial data
Trial was conducted in 18 countries.
Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDA▪In South Africa, preterm birth rate was 8.3% (39/469) in RSVpreF recipients
vs 4.0% (19/471) placebo recipients
▪In US, preterm birth rate was 5.7% (94/1654) in RSVpreF recipients vs. 5.3%
(87/1644) in placebo recipients
25VRBPAC discussion regarding preterm births: Pfizer
RSVpreF vaccine
▪An imbalance was seen in preterm births in both phase 2b and phase 3
trials, but the imbalance was not statistically significant
▪Preterm birth rate in trials was lower than background incidence rate of
preterm birth (~10% in US), but the trial had multiple exclusion criteria
selecting for a population at lower risk of preterm birth
▪Trial was underpowered to detect a 20% relative increase in preterm birth
181st Meeting of the Vaccines and Related Biological Products Advisory Committee –YouTube
Preterm Birth | Maternal and Infant Health | Reproductive Health | CDC
26VRBPAC discussion regarding preterm births: Pfizer
RSVpreF vaccine (cont.)
▪Imbalance was still present but less pronounced when comparing
prevalence of low birth weight
▪Most preterm births were late preterm ( ≥34 to <37 weeks)
▪Most preterm births were >30 days after vaccination
▪Preterm birth imbalance was most prominent in a single country, South
Africa
▪VRBPAC voted 14 -0 that the data supported effectiveness of Pfizer
maternal RSVpreF and voted 10 -4 that data supported safety
181st Meeting of the Vaccines and Related Biological Products Advisory Committee -YouTube
27Other considerations: Inflammatory neurologic events
Pfizer RSVPreF Vaccine
▪Same Pfizer RSV vaccine, formulation and dose approved for use in older adults
▪Within the main phase 3 trial for this product among adults ages ≥ 60 years (RENOIR)
a potential neurologic safety signal was identified
▪A total of 3 cases of potential inflammatory neurologic events were recorded among
20,255 investigational vaccine recipients across all clinical trials. No cases were
observed among placebo recipients.
https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023 -06-21-23/06 -RSV-Adults -Melgar -508.pdf)
28Other considerations: Inflammatory neurologic events
Pfizer RSVPreF Vaccine (cont.)
▪No Guillain -Barré Syndrome (GBS) or other demyelinating events were
reported in the phase 2b or 3 trials among pregnant people1
▪Background rate of GBS in pregnant people is much lower than among
older adults2,3
–Incidence rate of GBS in pregnant people in the Vaccine Safety Datalink during
2004 -2015: 2.8 (95% CI 0.5 –9.3) per million person -years (based on 2 cases)2
1.Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDA
2.Myers TR, McCarthy NL, Panagiotakopoulos L, Omer SB. Estimation of the Incidence of Guillain -Barré Syndrome During Pregnancy in the United States. Open Forum
Infect Dis. 2019 Mar 15;6(3):ofz071. doi: 10.1093/ ofid/ofz071.
3.Sejvar JJ, Baughman AL, Wise M, Morgan O. Population Incidence of Guillain -Barré Syndrome: A Systematic Review and Meta -Analysis. Neuroepidemiology
2011;36:123 –133
29Benefits and Harms Pfizer Maternal RSVPreF Vaccine
▪How substantial are the desirable anticipated effects?
–How substantial are the anticipated effects for:
•Medically attended RSV -associated lower respiratory infection in infants
•Hospitalization for RSV -associated lower respiratory tract infection in
infants
•ICU admission from RSV hospitalization in infants
•Mechanical ventilation from RSV hospitalization in infants
•RSV-associated death in infants
•All-cause hospitalization for lower respiratory tract infection in infants
•All-cause medically attended lower respiratory tract infection in infants
Minimal Small Moderate Large Varies Don’t know
30Benefits and Harms Pfizer Maternal RSVPreF Vaccine
▪How substantial are the undesirable anticipated effects?
–How substantial are the anticipated effects for:
•Serious adverse events in pregnant women
•Reactogenicity (3+ or higher) in pregnant women
•Serious adverse events in infants
•Preterm birth
Minimal Small Moderate Large Varies Don’t know
Minority Opinion
31Benefits and Harms Pfizer Maternal RSVPreF Vaccine
▪Do the desirable effects outweigh the undesirable effects?
–What is the balance between the desirable effects relative to the
undesirable effects?
Favors intervention (Pfizer Maternal RSVPreF
Vaccine)
Favors comparison (No intervention)
Favors both
Favors neither
Unclear
EtRDomain: Values
Criterion 1: Does the target population feel that the desirable effects are
large relative to undesirable effects?
Criterion 2: Is there important uncertainty about, or variability in, how
much people value the main outcomes?
33University of Iowa, RAND, and CDC Values Survey,
December 21, 2022 -January 2, 2023
▪523 participants
–Pregnancy status:*
•58.1% currently pregnant
•44.9% given birth in the last 12 months
–Race and Ethnicity:*
•66.0% Non -Hispanic White
•16.5% Non -Hispanic Black
•9.8% Hispanic
•7.7% Other Race/Ethnicity
▪68% of respondents had knowledge of RSV prior to taking survey
*Participants were able to select all applicable answer choices.
CDC and University of Iowa/RAND survey, unpublished
3461% of respondents said they ‘definitely’ or ‘probably’
would get an RSV vaccine while pregnant
CDC and University of Iowa/RAND survey, unpublished
35Among those who did not respond that they “definitely would” get an RSV
vaccine while pregnant, safety concerns, lack of RSV knowledge, and concerns
about vaccination causing or intensifying RSV infection were the top reasons
for not wanting an RSV vaccine during pregnancy
CDC and University of Iowa/RAND survey, unpublished
3622% of respondents did not want any vaccines or were unsure about how
many vaccines they would be willing to get in the same healthcare visit
during pregnancy
Prefer not to say
0%Unsure
10%No vaccines
12%One vaccine
17%Two vaccines
32%
Three vaccines
9%Four vaccines
20%
0%10%20%30%40%50%60%70%80%90%100%% of respondents (n=523)
CDC and University of Iowa/RAND survey, unpublished
37
Tdap vaccine coverage among pregnant women (n=838),
by race and ethnicity —Internet Panel Survey, United
States, April 2020 –April 2022
Flu, Tdap, and COVID -19 Vaccination Coverage Among Pregnant Women –United States, April 2022 | FluVaxView | Seasonal Influenza (Flu) | CDC
38Values
▪Criterion 1: Do pregnant people feel that the desirable effects are large
relative to undesirable effects?
No Probably No Probably Yes Yes Varies Don’t know
39Values
▪Criterion 2: Is there important uncertainty about, or variability in, how
much pregnant people value the main outcomes?
Important uncertainty or variability
Probably important uncertainty or variability
Probably not important uncertainty or variability
No important uncertainty or variability
No known undesirable outcomes
Minority Opinion
EtRDomain: Acceptability
Is the intervention acceptable to key stakeholders?
41Maternity healthcare professionals survey —England,
2019
▪Obstetrician and midwife support of RSV vaccine, if it was routinely
recommended:
–47% definitely
–34% likely
–14% not sure
–4% unlikely
–0.5% very unlikely
Wilcox, CR; Calvert, A; Metz, J et al. Attitudes of Pregnant Women and Healthcare Professionals Toward Clinical Trials and Routine Implementation of Antenatal Vacci nation
Against Respiratory Syncytial Virus: A Multicenter Questionnaire Study. The Pediatric Infectious Disease Journal 38(9):p 944 -951, September 2019. | DOI:
10.1097/INF.0000000000002384
42Acceptability
▪Is RSV prevention with Pfizer maternal RSVPreF vaccine acceptable to
key stakeholders?
No Probably No Probably Yes Yes Varies Don’t know
EtRDomain: Feasibility
Is the intervention feasible to implement?
44Storage and handling requirements
▪Supplied as single 0.5 mL dose, or as a 5 -pack or 10 -pack of single -dose
kits
▪Reconstitution required: single dose vial of lyophilized powder,
reconstitution supplies included in kit
▪Product should be refrigerated (2 –8°C) in original container, protected
from light
▪After reconstitution, the product should be administered within 4
hours, otherwise discarded
ShowLabeling.aspx (pfizer.com) and Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Presentation -Bivalent RSV Prefusion F
Vaccine for Maternal Immunization to Protect Infants (fda.gov)
45Timing of RSVPreF vaccination during pregnancy
▪Trial dosing was between 24 through 36 weeks gestation
▪Median gestational age at vaccination in phase 3 trial was 31 weeks1
▪Administration of maternal RSVPreF vaccine during regularly scheduled
prenatal visits and bundling with recommended screening tests and
other recommended vaccinations could also improve feasibility
–Tdap recommended every pregnancy, preferably during the early part
of gestational weeks 27 through 362
–Glucose challenge test recommended at 26 -28 weeks gestation3
1. FDA. Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Presentation -Review of Efficacy and Safet y of Respiratory Syncytial
Virus Vaccine (ABRYSVO) (fda.gov)
2. CDC, https://www.cdc.gov/vaccines/vpd/dtap -tdap -td/hcp/recommendations.html
3. US HHS OASH, https://www.womenshealth.gov/pregnancy/youre -pregnant -now -what/prenatal -care -and-
tests#:~:text=Typically%2C%20routine%20checkups%20occur%3A,for%20weeks%2036%20to%20birth
46Efficacy against medically attended RSV -associated
lower respiratory tract disease by gestational age at
vaccination
Subgroup Gestational Age at
VaccinationRSVpreF
(N= 3495)
nRSVpreF
(N= 3495)
# cases (%)Placebo
(N=3480)
nPlacebo
(N=3480)
# cases (%)VE (%) (95% CI)
Interim analysis at 180 days -- -- -- -- --
≥24 weeks to <28 weeks 890 22 (2.5) 866 27 (3.1) 20.7 ( -44.6, 57.0)
≥28 weeks to <32 weeks 1030 11 (1.1) 1070 35 (3.3) 67.4 (34.2, 85.0)
≥32 weeks to ≤36 weeks 1572 24 (1.5) 1539 55 (3.6) 57.3 (29.8, 74.7)
Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Presentation -Review of Efficacy and Safety of Respiratory Syncytial Virus Vaccine (ABRYSVO)
(fda.gov)Source: adapted from Pfizer 1008 CSR
Abbreviations: RSV= respiratory syncytial virus; VE= vaccine efficacy; CI= confidence interval
Note: this subgroup analysis did not appear in the FDA Briefing Document
47Potential considerations for timing of RSV vaccine
dosing during the year
▪RSV vaccine dosing could be implemented for pregnant people as a
seasonal campaign or year -round
▪Year -round dosing
–Simplify implementation and potentially increase vaccine uptake
–Protect infants in the event of atypical RSV seasonality
–Is less cost -effective
▪Limited benefit for doses given during March -May changes benefit/risk
calculation
48Potential considerations for timing of RSV vaccine
dosing during the year (cont.)
▪Some U.S. jurisdictions have different or less predictable RSV
seasonality, and recommendations for RSV vaccine dosing in those
jurisdictions would need to account for that
–Tropical climates: parts of Florida, Puerto Rico, U.S. Virgin Islands,
Hawaii, Guam, and U.S. -affiliated Pacific Islands
–Alaska: RSV seasonality is less predictable, and the duration of RSV
activity is often longer than the national average
49Simultaneous administration of RSV vaccines in
pregnant people
▪Pregnant people may potentially be eligible to receive RSV, Tdap,
COVID -19, and influenza vaccines at same visit
▪No available data on simultaneous administration of RSVpreF vaccine in
pregnant people and limited data in non -pregnant people
▪According to CDC’s immunization general best practices, age -
appropriate vaccinations can be administered simultaneously, with two
specific exceptions1,2
1. In persons with anatomic or functional asplenia and/or HIV infection, quadrivalent meningococcal conjugate vaccine (MCV4) -D (MenACWY -D, Menactra ) and
pneumococcal conjugate vaccine (PCV)13 (PCV13, Prevnar 13) should not be administered simultaneously. In patients recommended toreceive both PCV13 and PPSV23,
the 2 vaccines should not be administered simultaneously. ACIP Timing and Spacing Guidelines for Immunization | CDC
50Available data on simultaneous administration with
Pfizer RSVpreF vaccine
▪Pfizer Phase 2b study in healthy non-pregnant women ages 18 -49 on
coadministration of Tdap and Pfizer RSVpreF1
–Coadministration of Tdap and Pfizer RSVpreF led to decreased immune response to
pertussis components (i.e. non -inferiority criteria were not met)
▪Phase 3 study in non-pregnant adults ages ≥65 years on coadministration of
RSVpreF and adjuvanted seasonal quadrivalent influenza vaccine2
–Non-inferiority criteria were met for antibody titers against all 4 influenza strains,
as well as RSV -A and RSV -B
▪No safety concerns in either trial
▪Neither trial evaluated efficacy (not powered)
1. Peterson et. al. Safety and Immunogenicity of a Respiratory Syncytial Virus Prefusion F Vaccine When Coadministered With a Te tanus, Diphtheria, and Acellular Pertussis
Vaccine, The Journal of Infectious Diseases, Volume 225, Issue 12, 15 June 2022, Pages 2077 –2086 ,https://doi.org/10.1093/infdis/jiab505
2. Safety and Immunogenicity of RSVpreF Coadministered With SIIV in Adults ≥65 Years of Age -Full Text View -ClinicalTrials.gov
51Pertussis immunogenicity and co -administration in
adolescents and adults
▪There is no accepted correlate of protection for pertussis vaccination
–In the absence of a correlate of protection, non -inferiority is used to assess
immunogenicity of co -administration
–Clinical significance of failing to meet non -inferiority for pertussis is unclear
▪Some studies in adolescents and adults looking at Tdap coadministration
with other vaccines, including meningococcal and influenza vaccines, failed
to demonstrate non -inferiority against at least one pertussis antibody, but
coadministration is still recommended
▪Unclear how this might impact protection against pertussis from maternal
Tdap when co -administered with RSVpreF
Liang JL, Tiwari T, Moro P , et al. Prevention of Pertussis, Tetanus, and Diphtheria with Vaccines in the United States: Recom men dations of the Advisory Committee on
Immunization Practices (ACIP). MMWR Recomm Rep 2018;67(No. RR -2):1–44. DOI: http://dx.doi.org/10.15585/mmwr.rr6702a1 external icon
52
Place of Flu, Tdap, COVID -19 Vaccination among
Pregnant Women, United States, Internet Panel
Survey, April 2022
Flu, Tdap, and COVID -19 Vaccination Coverage Among Pregnant Women –United States, April 2022 | FluVaxView | Seasonal Influenza (Flu) | CDC“Other place” includes other medical or non -medical place, including school or special site for COVID -19 vaccination
53Availability of vaccines to pregnant people by practice
type
▪Survey of health care providers conducted in Fall 2022
Provider type (%)
Total
(n=1,538)Family
Practitioner/
Internist Pediatrician OB/GYN NP/PA
Tdap 72% 73% 79% 74% 58%
COVID -19 53% 56% 66% 40% 49%
Influenza 81% 85% 83% 74% 67%
Ob/Gyn =Obstetrician -Gynecologist; NP/PA: Nurse Practitioner or Physician’s Assistant
Unpublished data, Fall 2022 DocStylesProportion of practices that offer or administer vaccinations on site to pregnant patients
54Feasibility
▪Is Pfizer Maternal RSVPreF vaccine feasible to implement among
pregnant people at 24-36 weeks gestation?
No Probably No Probably Yes Yes Varies Don’t know
Minority Opinion
EtRDomain: Resource Use
Is the intervention a reasonable and efficient allocation of resources?
56Summary of Economic Analysis of RSVPreF in Pediatric
Populations
▪RSVPreF has the potential to be cost -effective
–Base case ICER: $214,087/QALY
▪Results sensitive to:
–Rate of prematurity
–Cost per dose
–Efficacy
–QALYs lost
–Timing of vaccination: year -round vs seasonal (e.g., June -February)
ICER: Incremental cost -effectiveness ratio; QALY: Quality -adjusted life year
57Resource Use
▪Is Pfizer Maternal RSVPreF vaccine use among pregnant people at 24 –
36 weeks gestation a reasonable and efficient allocation of resources?
No Probably No Probably Yes Yes Varies Don’t know
EtRDomain: Equity
What would be in the impact of the intervention on health equity?
59Population -based hospitalization rates among infants <6 months
old with laboratory -confirmed RSV by race and ethnicity, RSV -NET,
2018 –2019 to 2021 –2022
▪Hospitalization rates among infants <6 months old differ by race and ethnicity but vary by
season
▪Rates were not adjusted for RSV testing practices and thus may underrepresent RSV
hospitalization rates but should not affect distributions by race and ethnicity
RSV-NET: unpublished data. Surveillance was conducted from October –April for the 2018 –19 and 2019 –20 seasons, October –September for the 2020 –21 season, and October –
September excluding May –June for the 2021 –22 season. Rates were not adjusted for RSV testing practices; testing practices may di ffer by racial and ethnic groups and may have
changed over time. Black, White, Asian/Pacific Islander children were categorized as non -Hispanic; Hispanic children could be of any race.
0246810121416
2018–2019 2019–2020 2020–2021 2021–2022Rate per 1,000 population
Non-Hispanic Black Hispanic Non-Hispanic White Non-Hispanic Asian/Pacific Islander
6001234567
2018–2019 2019–2020 2020–2021 2021–2022Rate per 1,000 population
Non-Hispanic Black Hispanic Non-Hispanic White Non-Hispanic Asian/Pacific IslanderPopulation -based ICU admission rates among infants <6 months
old with laboratory -confirmed RSV by race and ethnicity, RSV -
NET, 2018 –2019 to 2021 –2022
RSV-NET: unpublished data. Surveillance was conducted from October –April for the 2018 –19 and 2019 –20 seasons, October –September for the 2020 –21 season, and October –
September excluding May –June for the 2021 –22 season. Rates were not adjusted for RSV testing practices; testing practices may di ffer by racial and ethnic groups and may have
changed over time. Black, White, and Asian/Pacific Islander children were categorized as non -Hispanic; Hispanic children could b e of any race.ICU admission rates among Non -Hispanic Black infants <6 months
old were 1.2–1.6x higher than among Non -Hispanic White infants

61Seasonal rate of RSV -associated hospitalizations per
1,000 children among American Indian and Alaska
Native children <5 years of age, Nov 2019 -May 2020
(SuNA )*
*Hartman et al, RSV2022 12thInternational Symposium, Belfast 9/29/2022 -10/2/2022; Atwell et al. RSV among American Indian and Alaska Native children: 2019 -20
(manuscript in press) SuNA = RSV Surveillance among Native American Persons
**Incidence of RSV -associated hospitalization in 2019 -2020 included for comparison. NVSN = New Vaccine Surveillance Network.
Age  Chinle, Arizona   Whiteriver,
Arizona  Anchorage, Alaska  Yukon -Kuskokwim
Delta, Alaska  NVSN** for
comparison
0-5 Months  83.0 (52.0, 132.5)  70.4 (36.3, 136.6)  35.7 (20.4, 62.6)  132.3 (98.2, 178.1)  21.6 (20.0 , 23.3)
6-11 Months  61.6 (35.9, 105.8)  90.1 (50.0, 162.3)  0.0 (0.0, 10.8)  91.6 (64.0, 131.0)  8.2 (7.1 , 9.3)
0-11 Months  71.8 (50.4, 102.4)  80.6 (51.9, 125.2)  19.2 (11.2, 33.0)  112.2 (89.3, 141.0)  14.9 (13.9 , 16.0)
12-23 Months  42.1 (27.2, 65.3)  38.7 (22.0, 68.1)  15.6 (8.7, 27.7)  26.4 (16.6, 41.8)  4.5 (3.9 , 5.2)
24-59 Months  10.9 (6.8, 17.4)  8.2 (4.2, 16.0)  1.1 (0.3, 3.8)  5.9 (3.2, 10.9)  1.2 (1.2 , 1.5)
0-59 Months  27.2 (21.4, 34.4)  25.4 (18.7, 34.5)  7.7 (5.3, 11.1)  32.7 (26.9, 39.7)  4.6 (4.3, 4.8)

62Insurance coverage for vaccinations among pregnant
people
▪All ACIP -recommended vaccinations are covered without cost -sharing for adults in
the Affordable Care Act (ACA) adult group who receive all essential health benefits1
▪Beginning on October 1, 2023, coverage of all approved ACIP -recommended adult
vaccines and vaccine administration, without cost sharing, will be mandatory for
both Medicaid and the Children’s Health Insurance Program under section 11405 of
the Inflation Reduction Act (IRA) (Pub. L. 117 -169).
▪Currently, most state Medicaid agencies cover at least some ACIP -recommended
adult immunizations for those not subject to essential health benefits, but may not
cover all recommended vaccines.
1 Quality of Care Vaccines | Medicaid
63Medicaid coverage among pregnant people
▪By federal law, all states provide Medicaid coverage for pregnancy -
related services to pregnant women with incomes up to 138% of the
federal poverty level1
▪In 2020, 42.0% of mothers had Medicaid at the time of birth2
▪In 2020, about 1 in 9 (11.6%) women of childbearing age (aged 15 -44
years) was uninsured in the United States3
1 Medicaid Coverage for Women | KFF
2 Medicaid coverage of births: United States, 2020 | PeriStats | March of Dimes
3 Uninsured women: United States, 2010 -2020 | PeriStats | March of Dimes
64Equity
▪What would be the impact of Pfizer Maternal RSVPreF vaccine on
health equity?
Reduced
Probably reduced
Probably no impact
Probably increased
Increased
Varies
Don’t know
Summary
66Evidence to Recommendations (EtR) Framework
EtR Domain Question(s) Work Group Judgements
Public Health Problem Is the problem of public health importance? Yes
Benefits and Harms How substantial are the desirable anticipated effects? Moderate to large
How substantial are the undesirable anticipated effects? Small vs Don’t Know
Do the desirable effects outweigh the undesirable effects? Favors intervention vs Unclear
Values Does the target population feel the desirable effects are large
relative to the undesirable effects?Probably Yes
Is there important variability in how patients value the
outcome?Probably important
uncertainty or variability
Acceptability Is the intervention acceptable to key stakeholders? Probably yes or Yes
Feasibility Is the intervention feasible to implement? Probably yes
Resource Use Is the intervention a reasonable and efficient allocation of
resources?Probably yes
Equity What would be in the impact of the intervention on health
equity?Probably increased
67Evidence to Recommendations Framework
Summary: Work Group Interpretations
Balance of
ConsequencesUndesirable
consequences
clearly
outweigh
desirable
consequences
in most
settingsUndesirable
consequences
probably
outweigh
desirable
consequences
in most settingsThe balance
between
desirable
and
undesirable
consequences
is closely
balanced or
uncertainDesirable
consequences
probably
outweigh
undesirable
consequences
in most settingsDesirable
consequences
clearly
outweigh
undesirable
consequences
in most settingsThere
is insufficient
evidence
to determine
the balance of
consequences
Minority Opinion
68Evidence to Recommendations Framework
Summary: Work Group Interpretations
Type of
RecommendationWe do not
recommend the
interventionWe recommend the
intervention for
individuals based on
shared clinical
decision -makingWe recommend the
intervention
Minority Opinion
69Summary of WG interpretations
▪Efficacious vaccine that can prevent RSV lower respiratory tract infection in
young infants
▪WG expressed concern that the Pfizer trial was underpowered to detect a
20% difference in preterm births between vaccine and placebo recipients
▪Interpretation of these overarching themes varied:
–Some members of the WG expressed concern that the data were insufficient to
determine the safety of this vaccine
–Others stressed this vaccine can provide benefit by preventing RSV lower
respiratory tract infection in infants and the difference in preterm births was
not statistically significant
70Summary of WG interpretations (cont.)
▪Imbalance in preterm birth was most prominent in a single country, South
Africa
▪Imbalance in preterm births was not seen in high -income countries
▪Imbalance was still present but less pronounced when comparing
prevalence of low birth weight
▪Most preterm births were >30 days after vaccination
71Summary of WG interpretations (cont.)
▪WG discussed considering a narrower recommended dosing window
–Some expressed support for starting dosing at a later gestational age within
24–36-week window used in the trial as this could mitigate potential risk of
early preterm birth until additional safety data are available
–Others expressed concern that this could leave preterm infants who are at
higher risk of severe RSV disease unprotected
▪Aligning RSVpreF vaccine dosing during pregnancy with Tdap
administration could improve feasibility
▪All WG members endorsed the importance of post -introduction vaccine
safety monitoring
72ACIP Policy Question
▪Should vaccination with Pfizer RSVPreF vaccine (120µg antigen, 1 dose
IM given 24 –36 weeks gestation) be recommended for pregnant people
to prevent RSV disease in infants?
Summary of proposed clinical
considerations for use of Pfizer RSVpreF
vaccine during pregnancy
74Proposed clinical considerations: Timing of dosing
during pregnancy and simultaneous administration
▪Proposed dosing interval for RSVpreF vaccine is 24 –36 weeks (aligned with
trials)
▪Healthcare providers could consider aligning RSVpreF vaccine dosing during
pregnancy with Tdap administration for feasibility of implementation
▪RSVpreF vaccine can be administered with other recommended vaccines
(e.g., influenza, COVID -19) without regards to timing, including
simultaneous vaccination on same clinic day
75Proposed clinical considerations: Timing of dosing
during the year
▪RSVpreF vaccine should be offered to pregnant people during June -
February in the continental United States
▪Healthcare providers can consider offering RSVpreF vaccine year -round
–For ease of implementation
–If RSV seasonality is unpredictable
–In jurisdictions with different RSV seasonality than continental U.S.
76Proposed clinical considerations: Additional vaccine
doses in subsequent pregnancies
▪Currently there are no data available on
–Efficacy of the first lifetime dose during subsequent pregnancies
–Safety of additional doses given in subsequent pregnancies
▪WG felt that it was too early decide whether additional doses should
be given in subsequent pregnancies given the lack of data
▪Additional data are needed to inform whether additional doses in
subsequent pregnancies would be indicated, and recommendations
can be updated in the future
77Acknowledgements
Jefferson Jones
Lauren Roper
Meredith McMorrow
Mila Prill
Monica Godfrey
Michael Melgar
Amadea Britton
Amanda Payne
Megan Wallace
Danielle Moulia
Morgan Najdowski
David Hutton
Jamison Pike Andrew Leidner
Ismael Ortega -Sanchez
Karen Broder
Naomi Tepper
Heidi Moline
Amber Winn
Monica Patton
Jenny Milucky
Fiona Havers
Rebecca Morgan
Doug Campos -Outcalt
Patricia Wodi
Sascha Ellington
78Note
Weacknowledge that not every person who can become pregnant identifies as a
woman. Although we try to use gender -neutral language as often as possible, much of
the research available currently refers only to “women” when discussing the ability to
become pregnant. When citing research, we refer to the language used in the study. In
these cases, “woman” refers to someone who was assigned female at birth. For clarity
in terminology, “maternal” is used to identify the person who is pregnant or
postpartum throughout this presentation; the authors are aware that pregnancy is not
equated with the decision to parent nor do all parents who give birth identify as
mothers.
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.

Extra slides for GRADE
Centers for Disease Control and Prevention
Grading of Recommendations, Assessment,
Development, and Evaluation (GRADE):
Pfizer Maternal RSVPreF Vaccine
Update: May 19, 2023
82Evidence Retrieval, conducted as of April 10, 2023
Records screened*
(n=161)Duplicates removed
(n=7)
Studies irrelevant
(n=139)Full text studies
assessed for
eligibility
(n=12)Studies excluded
(n=10)
7 wrong intervention
3 wrong patient population
Records included
in evidence
synthesis
(n=2)
*Medline (OVID), Embase (OVID), Cochrane Library, CINAHL ( EbscoHost ), Scopus, clinicaltrials.gov
83▪High certainty: We are very confident that the true effect lies close to that
of the estimate of the effect.
▪Moderate certainty: We are moderately confident in the effect estimate:
The true effect is likely to be close to the estimate of the effect, but there is
a possibility that it is substantially different.
▪Low certainty: Our confidence in the effect estimate is limited: The true
effect may be substantially different from the effect estimate.
▪Very low certainty: We have very little confidence in the effect estimate:
The true effect is likely to be substantially different from the estimate of
the effect.
NOTE: Evidence type is not measuring the quality of individual studies, but how much certainty we
have in the estimates of effect across each outcome.GRADE Evidence Type
84GRADE Evidence Type
▪Initial evidence type (certainty level) determined by study design
–Initial evidence high certainty: A body of evidence from randomized
controlled trials
–Initial evidence low certainty: A body of evidence from observational
studies
▪The certainty of evidence may be downgraded due to risk of bias,
inconsistency, indirectness, imprecision, or publication bias. For non -
randomized studies, the certainty may be rated up for presence of dose -
response gradient, large or very large magnitude of effect, and opposing
residual confounding.
NOTE: Evidence type is not measuring the quality of individual studies, but how much certainty we
have in the estimates of effect across each outcome.
Benefits
86Outcome 1: Medically attended RSV -associated lower
respiratory tract infection in infants (n=1 study)
▪ Pfizer phase 3 randomized controlled trial (RCT), MATISSE1
▪ Trial locations: Argentina, Australia, Brazil, Canada, Chile, Denmark, Finland, Gambia, Japan, Republic of Korea,
Mexico, Netherlands, New Zealand, Philippines, South Africa, Spain, Taiwan, United States
– 45% of participants from United States
▪ Study enrollment and efficacy follow -up occurred June 17, 2020, to October 2, 2022
▪ Data evaluated: data cut -off September 30, 2022; mean follow -up in infant participants 11.97 months after
birth (range: 0.0, 24.3)
▪ Infant evaluable efficacy set: 3,495 in vaccine arm; 3,480 in placebo arm
▪ Exclusion criteria of certain conditions may not represent all pregnant people and their infants in the United
States
▪ Placebo was not a saline placebo, but a lyophile match to the vaccine consisting of excipients matched to
those used in the RSVpreF vaccine formulation, minus the active ingredients
1Kampmann B, Madhi SA, Munjal I, et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants. N Engl J Med. 2023 Apr 5. doi: 10.1056/NEJMoa2216480.
87Outcome 1: Medically attended RSV -associated lower
respiratory tract infection in infants (n=1 study)
▪Medically attended visit (inclusive of inpatient and outpatient encounters) and ≥1:
–Fast breathing: respiratory rate ≥60 bpm (<2 months of age [60 days]) or ≥50
bpm (≥2 to 12 months of age)
–SpO2 measured in room air <95%
–Chest wall indrawing
▪Positive validated RT -PCR in central laboratory
▪Confirmed by endpoint adjudication committee (EAC)
SpO2= Peripheral capillary oxygen saturation
88Outcome 1: Medically attended RSV -associated lower
respiratory tract infection in infants (n=1 study)
Time period
after birthEvents/Vaccine
(n/N)Events/Placebo
(n/N)Vaccine efficacy (1 –RR)
(95% CI)Manufacturer calculated
vaccine efficacy1 (99.5% or
97.58% CI)
0–90 days after
birth224/3495 56/3480 57.3% (31.3, 73.5) 57.1% (14.7, 79.8)
0–120 days after
birth35/3495 81/3480 57.0% (36.2, 71.0) 56.8% (31.2, 73.5)
0–150 days after
birth47/3495 99/3480 52.7% (33.3, 66.5) 52.5% (28.7, 68.9)
0–180 days after
birth57/3495 117/3480 51.5% (33.7, 64.5) 51.3% (29.4, 66.8)
1Vaccine efficacy was calculated as 1−(P/[1−P]), where P is the number of cases of illness in the RSVpreF group divided by the total number of cases of illness. At 90 days,
99.5% confidence intervals (CIs) were used (determined by the alpha -spending function and adjusted with the use of the Bonferron i procedure), and at later intervals, 97.58%
CIs were used (based on a two -sided alpha level of 0.0483 adjusted with the use of the Bonferroni procedure).
2This outcome did not meet success criterion using manufacturer calculated VE (lower bound of CI was <20%)
89Outcome 1: Severe Medically attended RSV -associated
lower respiratory tract infection in infants (n=1 study)
▪Medically attended visit (inclusive of inpatient and outpatient encounters) and ≥1:
–Fast breathing (respiratory rate ≥70 (<2 month of age [60 days]) or ≥60 (≥2 to
12 months of age)
–SpO2 measured in room air <93%
–High -flow nasal cannula or mechanical ventilation
–ICU admission for >4 hours
–Unresponsive/unconscious
▪Positive validated RT -PCR in central laboratory
▪Confirmed by endpoint adjudication committee (EAC)
SpO2= Peripheral capillary oxygen saturation
90Outcome 1: Severe Medically attended RSV -associated
lower respiratory tract infection in infants (n=1 study)
Time period
after birthEvents/Vaccine
(n/N)Events/Placebo
(n/N)Vaccine efficacy (1 –RR)
(95% CI)Manufacturer calculated
vaccine efficacy1 (99.5% or
97.58% CI)
0–90 days after
birth6/3495 33/3480 81.9% (56.8, 92.4) 81.8% (40.6, 96.3)
0–120 days
after birth12/3495 46/3480 74.0% (51.1, 86.2) 73.9% (45.6, 88.8)
0–150 days
after birth16/3495 55/3480 71.0% (49.6, 83.4) 70.9% (44.5, 85.9)
0–180 days
after birth19/3495 62/3480 69.5% (49.1, 81.7) 69.4% (44.3, 84.1)
1Vaccine efficacy was calculated as 1−(P/[1−P]), where P is the number of cases of illness in the RSVpreF group divided by the total number of cases of illness. At 90 days,
99.5% confidence intervals (CIs) were used (determined by the alpha -spending function and adjusted with the use of the Bonferron i procedure), and at later intervals, 97.58%
CIs were used (based on a two -sided alpha level of 0.0483 adjusted with the use of the Bonferroni procedure).
91GRADE: Medically attended RSV -associated lower
respiratory infection in infants (n=1 study)
▪Measures of effect
–Relative Risk: 0.487 (0.332, 0.706)
–Absolute Risk1: 17 fewer per 1,000 (10 to 22 fewer); NNV: 59 (45, 100)
–Absolute Risk2: 119 fewer per 1,000 (68 to 154 fewer); NNV: 8 (6, 15)
–Absolute Risk3: 56 fewer per 1,000 (32 to 73 fewer); NNV: 18 (14, 31)
▪Concerns in certainty assessment: None
▪Evidence type: High
1Calculated using the observed outcomes in the placebo arm during the clinical trial follow -up (3.4%)
2Calculated using rate from Lively 2019 JPIDS , 2004 -2009 from 3 New Vaccine Surveillance Network (NVSN) sites from Nov -Apr season,
included if with acute respiratory infection (ARI), not restricted to LRTI.
3Calculated assuming 47.5% of ARI from Lively et al paper were LRTI ( Rainisch 2020 Vaccine )
NNV= Number needed to vaccinate
92Outcome 2: Hospitalization for RSV -associated lower
respiratory tract infection in infants (n=1 study)
▪Phase 3 RCT, MATISSE1
▪A respiratory tract infection due to RSV that results in hospitalization
▪Confirmed by endpoint adjudication committee (EAC)
1Kampmann B, Madhi SA, Munjal I, et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants. N Engl J Med. 2023 Apr 5. doi: 10.1056/NEJMoa2216480.
93Outcome 2: Hospitalization for RSV -associated lower
respiratory tract infection in infants (n=1 study)
Time period after
birthEvents/Vaccine
(n/N)Events/Placebo
(n/N)Vaccine efficacy (1 –RR)
(95% CI)Manufacturer calculated
vaccine efficacy1
(99.17% CI)
0–90 days after birth 10/3495 31/3480 67.9% (34.6, 84.2) 67.7% (15.9, 89.5)
0–120 days after
birth15/3495 37/3480 59.6% (26.6, 77.8) 59.5% (8.3, 83.7)
0–150 days after
birth17/3495 39/3480 56.6% (23.4, 75.4) 56.4% (5.2, 81.5)
0–180 days after
birth19/3495 44/3480 57.0% (26.5, 74.8) 56.8% (10.1, 80.7)
0–360 days after
birth238/3495 57/3480 33.6% (0.2, 55.8) 33.3% ( -17.6, 62.9)
1Vaccine 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 the Bonferroni procedure and accounting for the primary endpoints results. As a secondary endpoint, the criter ionfor vaccine efficacy was a
lower bound of the confidence interval >0%.
2This outcome did not meet success criterion using manufacturer calculated VE (lower bound of CI was <0%)
94GRADE: Hospitalization for RSV -associated lower
respiratory tract infection in infants (n=1 study)
▪Measures of effect
–Relative risk: 0.432 (0.193, 0.899)
–Absolute risk1: 7 fewer per 1,000 (1 to 10 fewer); NNV: 143 (100, 1,000)
–Absolute risk2: 11 fewer per 1,000 (2 to 15 fewer); NNV: 91 (67, 500)
▪Concerns in certainty assessment:
–Serious concern for imprecision due to the width of the confidence interval
containing estimates for which different policy decisions might be
considered
▪Evidence type: Moderate
1Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up.
2Calculated using the rate of acute respiratory infection (ARI) hospitalizations for infants 0 -5 months (2016 -2020 NVSN, unpubli shed)
95Outcome 5: RSV -associated death in infants (n=2
studies)
▪Phase 3 RCT, MATISSE and Phase 2b RCT (unpublished, data obtained from manufacturer)
▪Phase 2b RCT1,2
–Pregnant people ages 18 –49 in Argentina, Chile, South Africa and United States
•Infant safety set: 114 in vaccine arm (phase 3 formulation); 116 in placebo arm
▪1 RSV -associated death occurred in an infant in the placebo group recorded at day 120 after
birth in the Phase 3 study, no RSV -associated deaths occurred in the RSVPreF group
▪No RSV -associated deaths were recorded in the Phase 2b study among those who received
the phase 3 formulation or placebo
▪Outcome not included in GRADE
1Simões EAF, Center KJ, Tita ATN, et al. Prefusion F Protein –Based Respiratory Syncytial Virus Immunization in Pregnancy. N Engl J Med. 2022 Apr 28. doi:
10.1056/NEJMoa2106062.
2https://www.clinicaltrials.gov/ct2/show/study/NCT04032093
96Outcome 6: All -cause medically attended lower
respiratory tract infection in infants (n=1 study)
▪Phase 3 RCT, MATISSE1
▪Infant with any medically attended -RTI visit (inpatient or outpatient) AND
–Fast breathing (respiratory rate ≥60 bpm for <2 months of age [<60
days of age] or ≥50 bpm for ≥2 to <12 months of age) OR
–SpO2 <95% OR
–Chest wall indrawing
1Kampmann B, Madhi SA, Munjal I, et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants. N Engl J Med. 2023 Apr 5. doi: 10.1056/NEJMoa2216480.SpO2= Peripheral capillary oxygen saturation
97Outcome 6: All -cause medically attended lower
respiratory tract infection in infants (n=1 study)
Time period
after birthEvents/Vaccine
(n/N)Events/Placebo
(n/N)Vaccine efficacy
(1 –RR) (95% CI)Manufacturer calculated
vaccine efficacy1  (99.17% CI)
0–90 days after
birth2186/3495 200/3480 7.4% ( -12.4, 23.7) 7.0% ( -22.3, 29.3)
0–120 days after
birth2261/3495 278/3480 6.5% ( -10, 20.5) 6.1% ( -18.3, 25.5)
0–150 days after
birth2331/3495 349/3480 5.6% ( -8.9, 18.1) 5.2% ( -16.5, 22.8)
0–180 days after
birth2392/3495 402/3480 2.9% ( -10.7, 14.8) 2.5% ( -17.9, 19.4)
0–360 days after
birth2504/3495 531/3480 5.5% ( -5.8, 15.5) 5.1% ( -12.1, 19.6)
1Vaccine 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 the Bonferroni procedure and accounting for the primary endpoints results. As a secondary endpoint, the criter ionfor vaccine efficacy was a
lower bound of the confidence interval >0%.
2This outcome did not meet success criterion (lower bound of CI was <0%)
98GRADE: All-cause medically attended lower respiratory
tract infection in infants (n=1 study)
▪Measures of effect
–Relative risk: 0.975 (0.806, 1.179)
–Absolute risk*: 3 fewer per 1,000 (22 fewer to 21 more)
▪Concerns in certainty assessment
–Serious concern for imprecision due to the width of the confidence
interval containing estimates for which different policy decisions might
be considered
▪Evidence type: Moderate
*Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up. Abso lute risk estimates should be
interpreted in this context.
Harms
100Outcome 8: Serious adverse events in pregnant people
(n=2 studies)
▪Phase 3 RCT, MATISSE (unpublished, data obtained directly from
manufacturer)
–Maternal safety set: 3,682 participants in vaccine arm; 3,675 in
placebo arm
▪Phase 2b RCT (unpublished, data obtained directly from manufacturer)
–Maternal safety set: 115 participants in vaccine arm (phase 3
formulation); 117 in placebo arm
▪Follow up times for serious adverse events reported by maternal
participants were from vaccination through 6 months after delivery (Phase
3) or throughout the study (Phase 2b)
101Outcome 8: Serious adverse events in pregnant people
(n=2 studies)
101Trial Events/Vaccine
(n/N)Events/Placebo
(n/N)Relative Risk (95% CI)
Phase 3 598/3682 (16.2%) 558/3675 (15.1%) 1.07 (0.96, 1.19)
Phase 2b 7/115 (6.1%) 14/117 (12.0%) 0.51 (0.21, 1.21)
Serious adverse events in four vaccine recipients (pain in an arm followed by bilateral lower extremity pain, premature labor ,
systemic lupus erythematosus, and eclampsia) and in one placebo recipient (premature placental separation) were assessed by t he
investigator as being related to the injection. Based on review of the event narratives and temporal association of these events to
vaccination, FDA agreed with the investigator’s assessments that there was a reasonable possibility that these events were re lated
to the study intervention.
Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDA
102GRADE: Serious adverse events in pregnant people
(n=2 studies)
▪Measures of effect
–Relative risk: 1.06 (0.95, 1.17)
–Absolute risk*: 9 more per 1,000 (8 fewer to 26 more)
▪Concerns in certainty assessment
–Serious concern for imprecision due to the width of the confidence
interval containing estimates for which different policy decisions might
be considered
▪Evidence type: Moderate
*Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up. Abso lute risk estimates should be
interpreted in this context.
103Outcome 9: Reactogenicity (grade 3+) in pregnant
people (n=2 studies)
▪Phase 3 RCT, MATISSE and Phase 2b (unpublished, data obtained directly
from manufacturer)
▪Participants reported local and systemic reactions up to 7 days after
vaccination
104Outcome 9: Reactogenicity (grade 3+) in pregnant
people
104Trial Outcome Events/Vaccine
(n/N)Events/Placebo
(n/N)Relative Risk (95% CI)
Phase 3 Local events (grade 3+) 11/3660 (0.3%) 0/3639 (0%) 22.87 (1.35, 387.94)
Systemic events (grade 3+) 83/3663 (2.3%) 83/3640 (2.3%) 0.94 (0.70, 1.28)
Phase 2b Local events (grade 3+) 0/114 (0%) 0/117 (0%) 1.03 (0.02, 51.28)
Systemic events (grade 3+) 2/114 (1.8%) 4/117 (3.4%) 0.51 (0.10, 2.75)
Grade 3: prevents daily routine activity. For redness or swelling is >10 cm. For vomiting, requires intravenous hydration. Fo r
diarrhea, includes 6 or more loose stools in 24 hours. Grade 4: requires emergency room visit or hospitalization; for redness
included necrosis or exfoliative dermatitis; for swelling included necrosis.

105Outcome 9: Reactogenicity (grade 3+) in pregnant
people (n=2 studies)
▪Measures of effect
–Relative risk: 0.97 (0.72, 1.31)
–Absolute risk*:  1 fewer per 1,000 (6 fewer to 7 more)
▪Concerns in certainty assessment:
–Serious concern for indirectness as this data only includes systemic
reactions
▪Evidence type: Moderate
*Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up. Abso lute risk estimates should be
interpreted in this context.
106Outcome 10: Serious adverse events in infants (n=2
studies)
▪Phase 3 RCT, MATISSE (unpublished, data obtained directly from
manufacturer)
–Infant safety set: 3,568 in vaccine arm; 3,558 in placebo arm
▪Phase 2b RCT (unpublished, data obtained directly from manufacturer)
–Infant safety set: 114 in vaccine arm (phase 3 formulation); 116 in
placebo arm
107
Outcome 10: Serious adverse events in infants (n=2
studies)
Trial Events/Vaccine
(n/N)Events/Placebo
(n/N)Relative Risk (95% CI)
Phase 3 625/3568 (17.5%) 623/3558 (17.5%) 1.00 (0.90, 1.11)
Phase 2b 41/114 (36.0%) 38/116 (32.8%) 1.10 (0.77, 1.57)
No serious adverse events in infants were considered by the investigators to be related to the vaccine. For infant deaths in the
RSVpreF group, the FDA agreed with the investigator’s conclusions for 4 out of 5 of the infant deaths; however, for 1 case of
extreme prematurity in an infant born to an 18 -year -old mother at 10 days after vaccination who died from prematurity -related
complications, FDA was unable to exclude the possibility of the extreme prematurity and subsequent death being related to rec eipt
of the investigational product. No non -fatal SAEs in infant participants were considered related to maternal vaccination by FDA.
Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDA
108GRADE: Serious adverse events in infants (n=2 studies)
▪Measures of effect
–Relative risk: 1.01 (0.91, 1.11)
–Absolute risk*:  2 more per 1,000 (16 fewer to 19 more)
▪Concerns in certainty assessment
–Serious concern for imprecision due to the width of the confidence
interval containing estimates for which different policy decisions might
be considered
▪Evidence type: Moderate
*Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up. Abso lute risk estimates should be
interpreted in this context.
109Outcome 11: Preterm births (n=2 studies)
▪Phase 3 RCT, MATISSE and Phase 2b (unpublished, data obtained directly
from manufacturer)
–Gestational age at birth <37 weeks and <34 weeks
110Outcome: Preterm births (n=2 studies), Pfizer maternal
RSVpreF vaccine
110Publication Definition Events/Vaccine
(n/N)Events/Placebo
(n/N)Relative Risk (95% CI)
Phase 3<34 weeks 21/3568 12/3558 1.75 (0.86, 3.54)
<37 weeks 201*/3568 169/3558 1.19 (0.97, 1.45)
Phase 2b<34 weeks 0/115 1/117 0.34 (0.01, 8.24)
<37 weeks 6/115 3/117 2.03 (0.52, 7.94)
*When reported as an adverse event of special interest, 202 preterm births occurred in the vaccine arm; the relative risk is minimally changed at 1.19 (0.98, 1.45) when using this count
111Outcome: Preterm births (n=2 studies), Pfizer maternal
RSVpreF vaccine
▪Measures of effect
–Relative risk: 1.20 (0.99, 1.46)
–Absolute risk*:  9 more per 1,000 (from 0 fewer to 22 more)
▪Concerns in certainty assessment:
–Very se rious concern for imprecision due to the width of the
confidence interval containing estimates for which different policy
decisions might be considered and not meeting optimal information
size requirements
▪Evidence type: Low
*Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up. Abso lute risk estimates should be
interpreted in this context.
GRADE additional slides
113Inclusion/exclusion criteria for pregnant people -Phase 3 Trial
Inclusion Exclusion
Healthy women ≤49 years of age who are
between 24 0/7 and 36 0/7 weeks of gestation
on the day of planned vaccination, with an
uncomplicated, singleton pregnancy, who are at
no known increased risk for complications.
Willing and able to comply with scheduled visits,
treatment plan, laboratory tests, and other
study procedures.
Receiving prenatal standard of care based on
country requirements.
Had a fetal anomaly ultrasound examination
performed at ≥18 weeks of pregnancy with no
significant fetal abnormalities observed.
Determined by medical history, physical
examination, and clinical judgment to be
appropriate for inclusion in the study.
Documented negative HIV antibody test, syphilis
test, and hepatitis B virus (HBV) surface antigen
test during this pregnancy and prior to
randomization (Visit 1).
Intention to deliver at a hospital or birthing
facility where study procedures can be obtained.
Expected to be available for the duration of the
study and can be contacted by telephone during
study participation.
Participant is willing to give informed consent
for her infant to participate in the study.
Capable of giving signed informed consent
which includes compliance with the
requirements and restrictions listed in the
informed consent document (ICD) and in this
protocol OR If the maternal participant is
illiterate, a thumbprinted informed consent
must be obtained, which must be signed and
dated by an impartial witness who was present
throughout the entire informed consent process
confirming that the maternal participant has
been informed of all pertinent aspects of the
study.Prepregnancy body mass index (BMI) of >40 kg/m2. If prepregnancy BMI is not available, the BMI at the time of the first obste tric visit during the current pregnancy may be used.
Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindi cate intramuscular injection.
History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any compone nt of the investigational product or any related vaccine.
Current pregnancy resulting from in vitro fertilization.
Current pregnancy complications or abnormalities at the time of consent that will increase the risk associated with the parti cipation in and completion of the study, including but not limited
to the following:
Preeclampsia, eclampsia, or uncontrolled gestational hypertension.
Placental abnormality.
Polyhydramnios or oligohydramnios.
Significant bleeding or blood clotting disorder.
Endocrine disorders, including untreated hyperthyroidism or untreated hypothyroidism. This also includes disorders of glucose intolerance (eg, diabetes mellitus type 1 or 2) antedating
pregnancy or occurring during pregnancy if uncontrolled at the time of consent.
Any signs of premature labor with the current pregnancy or having ongoing intervention (medical/surgical) in the current preg nancy to prevent preterm birth.
Prior pregnancy complications or abnormalities at the time of consent, based on the investigator's judgment, that will increa se the risk associated with the participation in and completion of
the study, including but not limited to the following:
Prior preterm delivery ≤34 weeks' gestation.
Prior stillbirth or neonatal death.
Previous infant with a known genetic disorder or significant congenital anomaly.
Major illness of the maternal participant or conditions of the fetus that, in the investigator's judgment, will substantially increase the risk associated with the maternal or infant participant's
participation in, and completion of, the study or could preclude the evaluation of the maternal participant's response (inclu despositive serologic testing for regional endemic conditions
assessed during routine maternal care, as per local standards of care and obstetric recommendations).
Congenital or acquired immunodeficiency disorder, or rheumatologic disorder or other illness requiring chronic treatment with known immunosuppressant medications, including
monoclonal antibodies, within the year prior to enrollment.
Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation o r behavior or laboratory abnormality that may increase the risk
associated with study participation or investigational product administration or may interfere with the interpretation of stu dy results and, in the judgment of the investigator, would make
the participant inappropriate for entry into this study.
Participation in other studies involving investigational drug(s) within 28 days prior to consent and/or during study particip ation.
Receipt of monoclonal antibodies within the year prior to enrollment or the use of systemic corticosteroids for >14 days with in 28 days prior to study enrollment. Permitted treatments
include the receipt of severe acute respiratory syndrome coronavirus 2 (SARS -CoV-2) monoclonal antibodies, prednisone doses of < 20 mg/day for ≤14 days and, inhaled/nebulized, intra -
articular, intrabursal, or topical (skin or eyes) corticosteroids.
Current alcohol abuse or illicit drug use. Note: Marijuana use is not considered an exclusion criterion for the study when el icited in participant screening, though it may be considered illicit
in some locales.
Receipt of blood or plasma products or immunoglobulin (Ig), from 60 days before investigational product administration, or pl anned receipt through delivery, with 1 exception, Rho(D)
immune globulin (eg, RhoGAM), which can be given at any time.
Previous vaccination with any licensed or investigational RSV vaccine or planned. Note: Licensed COVID -19 vaccines or COVID -19 vaccines authorized for temporary or emergency use will
not be prohibited during the course of this study.
Investigator site staff members directly involved in the conduct of the study and their family members, site staff members ot herwise supervised by the investigator, or Pfizer employees,
including their family members, directly involved in the conduct of the study.
Participants who are breastfeeding at the time of enrollment.
114Inclusion/exclusion criteria for infants -Phase 3 Trial
Inclusion Exclusion
Evidence of a signed and dated informed consent document signed by the
parent(s)/legal guardian(s) OR If the infant participant's maternal
participant/parent(s)/legal guardian(s) is illiterate, a thumbprinted
informed consent must have been obtained, which must have been signed
and dated by an impartial witness who was present throughout the entire
informed consent process confirming that the maternal
participant/parent(s)/legal guardian(s) has been informed of all pertinent
aspects of the study for herself (maternal participant) and her fetus/infant
prior to taking part in the study.
Parent(s)/legal guardian(s) willing and able to comply with scheduled visits,
treatment plan, laboratory tests, and other study procedures.Infant who is a direct descendant (e.g., child or
grandchild) of the study personnel.
115Inclusion/exclusion criteria for pregnant people -Phase 2b
Inclusion -Pregnant people Exclusion -Pregnant people
Healthy women 18 to 49 years of age between 24
and 36 weeks of gestation on the day of planned
vaccination, with an uncomplicated pregnancy, who
are at no known increased risk for complications, and
whose fetus has no significant abnormalities
observed on ultrasound.
Willing and able to comply with scheduled visits,
treatment plan, laboratory tests, and other study
procedures.
Receiving prenatal standard of care.
Had an ultrasound performed at >=18 weeks of
pregnancy.
Had a negative urinalysis for protein and glucose at
the screening visit. Trace protein in the urine is
acceptable if the blood pressure is also normal.
Determined by medical history, physical examination,
screening laboratory assessment, and clinical
judgment to be appropriate for inclusion in the study.
Documented negative human immunodeficiency
virus antibody, hepatitis B virus surface antigen,
hepatitis C virus antibody, and syphilis tests at the
screening visit.
Body mass index of </=40 kg/m2 at the time of the
screening visit.
Capable of giving signed informed consent, which
includes compliance with the requirements and
restrictions listed in the informed consent document
and in this protocol.
Expected to be available for the duration of the study
and willing to give informed consent for her infant to
participate in the study.Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindi cate
intramuscular injection.
History of severe adverse reaction associated with a vaccine and/or severe allergic reaction to any component of the investig ational product
or any related vaccine.
History of latex allergy.
History of any severe allergic reaction.
Participants with known or suspected immunodeficiency.
Current pregnancy resulting from in vitro fertilization or other assisted reproductive technology.
A prior history of or known current pregnancy complications or abnormalities that will increase the risk associated with the participant's
participation in and completion of the study.
Major illness of the mother or conditions of the fetus that, in the investigator's judgment, will substantially increase the risk associated with
the participant's participation in, and completion of, the study or could preclude the evaluation of the participant's respon se.
Participant with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention including but not
limited to systemic or cutaneous lupus erythematosus, autoimmune arthritis/rheumatoid arthritis, Guillain -Barré syndrome, multip le
sclerosis, Sjögren's syndrome, idiopathic thrombocytopenia purpura, glomerulonephritis, autoimmune thyroiditis, giant cell ar teritis
(temporal arteritis), psoriasis, and insulin -dependent diabetes mellitus (type 1).
Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation o r behavior or
laboratory abnormality that may increase the risk associated with study participation or investigational product administrati on or may
interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inapp ropriate for entry
into this study.
Participation in other studies involving investigational drug(s) within 28 days prior to study entry and/or during study part icipation.
Participants who receive treatment with immunosuppressive therapy including cytotoxic agents or systemic corticosteroids (suc h as for
cancer or an autoimmune disease), or planned receipt of such treatment or agents during study participation. If systemic cort icosteroids have
been administered short term (<14 days) for treatment of an acute illness, participants should not be enrolled into the study until
corticosteroid therapy has been discontinued for at least 30 days before investigational product administration. Inhaled/nebu lized, intra
articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
Current alcohol abuse or illicit drug use.
Receipt of blood or plasma products or immunoglobulin, from 60 days before investigational product administration, or planned receipt
through delivery, with 1 exception, Rho(D) immune globulin (eg, RhoGAM), which can be given at any time.
Previous vaccination with any licensed or investigational RSV vaccine or planned receipt during study participation.
Laboratory test results at the screening visit outside the normal reference value for pregnant women according to their trime ster in
pregnancy.
Participants who are breastfeeding at the time of the screening visit.
116Inclusion/exclusion criteria for infants -Phase 2b
Inclusion -Infants Exclusion -Infants
Evidence of a signed and dated informed consent document signed
by the parent(s).
Parent(s) willing and able to comply with scheduled visits,
treatment plan, laboratory tests, and other study procedures.Infant who is a direct descendant (eg, child or grandchild) of the
study personnel.
117
Figure 1. Enrollment,
Randomization, Administration of
Vaccine or Placebo, and Follow -up
Kampmann B, Madhi SA, Munjal I, et al.
Bivalent Prefusion F Vaccine in
Pregnancy to Prevent RSV Illness in
Infants. N Engl J Med. 2023 Apr 5. doi:
10.1056/NEJMoa2216480.
118Table 1. Demographics of phase 3 trial
118
Kampmann B, Madhi SA, Munjal I, et al.
Bivalent Prefusion F Vaccine in
Pregnancy to Prevent RSV Illness in
Infants. N Engl J Med. 2023 Apr 5. doi:
10.1056/NEJMoa2216480.
119Severity scale for local reactions and systemic events
(maternal participants)
119
Kampmann B, Madhi SA, Munjal I, et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants. N Engl J Med. 2023 Apr 5. doi: 10.1056/NEJMoa2216480.
120Studies Included in the Review of Evidence
Last name first author,
Publication yearStudy design Country Age
mean
(SD)Total Population N intervention N comparison Outcomes Funding
Source
Kampmann B,
etal.plus unpublished
data obtained directly
from the manufacturer RCT Argentina, Australia,
Brazil, Canada, Chile,
Denmark, Finland,
Gambia, Japan,
Republic of Korea,
Mexico, Netherlands,
New Zealand,
Philippines, South
Africa, Spain, Taiwan,
United States29.0
(5.7)7,357 3,682 3,675 Medically attended
RSV-associated lower
respiratory infection in
infants; Hospitalization
for RSV -associated
lower respiratory tract
infection in infants;
RSV-associated death
in infants; All cause
medically attended
lower respiratory tract
infection in infants;
Serious adverse events
in pregnant people;
Reactogenicity in
pregnant people;
Serious adverse events
in infants; Preterm
birthPfizer
Pfizer, Phase 2 Trial
plus unpublished data
obtained directly from
the manufacturer RCT Argentina, Chile, South
Africa and the United
States27.1
(5.2)232 115 (phase 3
formulation)117 RSV-associated death
in infants; Serious
adverse events in
pregnant people;
Reactogenicity in
pregnant people;
Serious adverse events
in infants; Preterm
birth;Pfizer
121Summary of Studies Reporting Outcome 1: Medically attended
RSV-associated lower respiratory infection in infants
Last name
first author,
Publication
yearAge
mean
(SD)N
interventionN
comparisonComparator
VaccineAbsolute
difference/effect
estimate (99.58%
CI)Study
limitations
(Risk of Bias)
Kampmann B,
et al.29.0
(5.7)3495 3480 Placebo 17 fewer per
1,000 (10 to 22
fewer)None
122Summary of Studies Reporting Outcome 2: Hospitalization for
RSV-associated lower respiratory tract infection in infants
Last name first
author,
Publication
yearAge
mean
(SD)N
interventionN
comparisonComparator
VaccineAbsolute
difference/effect
estimate (99.17%
CI)Study
limitations
(Risk of Bias)
Kampmann B,
et al.29.0
(5.7)3495 3480 Placebo 7 fewer per 1,000
(1 to 10 fewer)None
123Summary of Studies Reporting Outcome 5: RSV -
associated death in infants
Last name first
author,
Publication
yearAge
mean
(SD)N
interventionN
comparisonComparator
VaccineAbsolute
difference/effe
ct estimateStudy
limitations
(Risk of Bias)
Kampmann B, et
al.29.0
(5.7)3495 3480 Placebo Not estimable
1 death in a
placebo
recipientN/A
Phase 2b RCT,
unpublished18-49
(range)114 116 Placebo Not estimable
0 deaths in trialN/A
124Summary of Studies Reporting Outcome 6: All cause medically
attended lower respiratory tract infection in infants
Last name first
author,
Publication
yearAge
mean
(SD)N
interventionN
comparisonComparator
VaccineAbsolute
difference/effect
estimate (99.17%
CI)Study
limitations
(Risk of Bias)
Kampmann B, et
al.29.0
(5.7)3495 3480 Placebo 3 fewer per 1,000
(22 fewer to 21
more)None
125Summary of Studies Reporting Outcome 8: Serious
adverse events in pregnant people
Last name first
author,
Publication
yearAge
mean
(SD)N
interventionN
comparisonComparator
VaccineAbsolute
difference/effect
estimateStudy
limitations
(Risk of Bias)
Kampmann B, et
al.29.0
(5.7)3682 3675 Placebo RR: 1.07 (0.96,
1.19)None
Phase 2b RCT 27.1
(5.2)115 117 Placebo RR: 0.51 (0.21,
1.21)None
126Summary of Studies Reporting Outcome 9:
Reactogenicity (grade 3+) in pregnant people
Last name first
author,
Publication
yearAge
mean
(SD)N
interventio
nN
comparisonComparator
VaccineAbsolute
difference/effect
estimateStudy
limitations
(Risk of Bias)
Kampmann B,
et al.29.0
(5.7)3663 3640 Placebo RR: 0.94 (0.70,
1.28)None
Phase 2b RCT 27.1
(5.2)114 117 Placebo RR: 0.51 (0.10,
2.75)None
127Summary of Studies Reporting Outcome 10: Serious
adverse events in infants
Last name first
author, Publication
yearAge median
(range)N intervention N comparison Comparator
VaccineAbsolute
difference/effect
estimateStudy
limitations (Risk
of Bias)
Kampmann B, et
al. 11.97
months
(0.0, 24.3) 3568 3558 Placebo RR: 1.00 (0.90,
1.11)None
Phase 2b RCT 114 116 Placebo RR: 1.10 (0.77,
1.57)None
128Summary of Studies Reporting Outcome 11: Preterm
birth
Last name first
author, Publication
yearAge mean
(SD)N intervention N comparison Comparator
VaccineAbsolute
difference/effect
estimateStudy
limitations (Risk
of Bias)
Kampmann B, et
al.11.97
months
(0.0, 24.3)3568 3558 Placebo RR: 1.19 (0.97,
1.45)None
Phase 2b RCT 115 117 Placebo RR: 2.03 (0.52,
7.94)None
129Grade Summary of Findings Table -Benefits
129№ of
studiesStudy designRisk of
biasInconsistency Indirectness ImprecisionOther
considerationsIntervention ComparisonRelative
(95% CI)Absolute
(95% CI)Importance Certainty
Medically attended RSV -associated lower respiratory infection in infants
1 Randomized
studiesNot serious Not serious Not serious Not serious None 57/3495 (1.6%) 117/3480
(3.4%)0.487
(0.332,
0.706)17 fewer
per 1,000
(10 to 22
fewer)Critical High
23.1% 119 fewer
per 1,000
(68 to 154
fewer)
11.0% 56 fewer
per 1,000
(32 to 73
fewer)
Hospitalizations RSV -associated lower respiratory infection in infants
1 Randomized
studiesNot serious Not serious Not serious Serious None 19/3495 (0.5%) 44/3480 (1.3%) 0.432
(0.193,
0.899)7 fewer per
1,000 (1 to
10 fewer)Critical Moderate
1.9% 11 fewer
per 1,000 (2
to 15 fewer)
All-cause medically attended lower respiratory infection in infants
1 Randomized
studiesNot serious Not serious Not serious Serious None 392/3495
(11.2%)402/3480
(11.6%)0.97 (0.85,
1.11)3 fewer per
1,000 (22
fewer to 21
more)Important Moderate
130Grade Summary of Findings Table -Harms
130№ of
studiesStudy design Risk of biasInconsiste
ncyIndirectness ImprecisionOther
considerationsIntervention comparisonRelative
(95% CI)Absolute
(95% CI)Importance Certainty
Serious adverse events in pregnant women
2 Randomized
studiesNot
seriousNot
seriousNot serious Serious None 605/3797
(15.9%)572/3792
(15.1%)1.06
(0.95,
1.17)9 more per
1,000 (8
fewer to 26
more)Critical Moderate
Reactogenicity (3+ or higher) in pregnant women
2 Randomized
studiesNot
seriousNot
seriousSerious Not serious None 85/3777
(2.3%)87/3757
(2.3%)0.97
(0.72,
1.31)1 fewer per
1,000 (6
fewer to 7
more)Important Moderate
Serious adverse events in infants
2 Randomized
studiesNot
seriousNot
seriousNot serious Serious None 625/3568
(17.5%)623/3558
(17.5%)1.01
(0.91,
1.11)2 more per
1,000 (16
fewer to 19
more)Critical Moderate
Preterm birth
2 Randomized
studiesNot
seriousNot
seriousNot serious Very
seriousNone 207/3683
(5.6%)172/3675
(4.7%)1.20
(0.99,
1.46)9 more per
1,000 (0
fewer to 22
more)Critical Low

Summary: Centers for Disease Control and Prevention Evidence to Recommendations Framework:  Pfizer Maternal RSVpreF Vaccine Katherine Fleming -Dutra, MD Co-Lead, Respiratory Syncytial Virus Vaccines -Pediatric/Maternal Work Group  Coronavirus and Other Respiratory Viruses Division National Center for Immunization and Respiratory Diseases June 22, 2023 2Evidence to Recommendations (EtR) Framework Policy Question ▪Should vaccination with Pfizer RSVPreF vaccine (120µg antigen, 1 dose  IM given 24 –36…


04 RSV Mat Ped Hutton 508

Economics of combined use of Pfizer
maternal RSVpreF vaccine and
nirsevimab
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 MichiganPresentation to the ACIP
June 22, 2023

Research team
University of Michigan
•David Hutton, PhD
•Lisa Prosser, PhD
•Angela Rose, MPH
•Kerra Mercon , MSCDC
•Jefferson Jones, MD, MPH, FAAP
•Mila Prill, MSPH
•Meredith McMorrow, MD, MPH,
FAAP
•Jamison Pike, PhD
•Katherine Fleming -Dutra, MD,
FAAP
•Ismael Ortega -Sanchez, PhD
•Fiona Havers, MD
•Betsy Gunnels, MSPH
•Andrew Leidner , PhD
2
Conflicts of interest statements
•Authors have no known conflict of interests.
3
Methods: Study questions
•Determine the cost -effectiveness of:
•Nirsevimab in children born to mothers who received RSVpreF at least 2
weeks prior to delivery
•RSVpreF for pregnant persons who will give nirsevimab to their newborns
•Single individual
•Evaluate by month of year
•Perspective: Societal
•Timeframe: 1 year (1 RSV season)
•Analytic horizon: infant’s lifetime
•Discount rate: 3%
4
Overview of nirsevimab
changes/additions
•Since February
•Nirsevimab cost $500/dose
•Nirsevimab reduces palivizumab use
•Old base case ICER: $ 102,805/QALY
•New base case ICER: $157,537/QALY
5
Methods: Intervention effectiveness
•NO evidence of efficacy on the combined use of
these products
•Assumption:
•Efficacy equal to the highest of nirsevimab or RSVpreF :
•Efficacy would not be higher than from the most effective
product
6
Methods: Intervention effectiveness
7* Assuming administration of nirsevimab at birth0%20%40%60%80%100%
0 2 4 6 8 10 12 14Hospitalization Efficacy
Months since birth
RSVPreF Both Nirsevimab
Incremental benefit of adding
nirsevimab on top of RSVpreF
8•For infants of persons vaccinated with RSVpreF
during pregnancy
0%20%40%60%80%100%
0 2 4 6 8 10 12 14Hospitalization Efficacy
Months since birth
RSVPreF Both NirsevimabMethods: Intervention effectiveness
9
Additional benefit of adding nirsevimab
* Assuming administration of nirsevimab at birth

0%10%20%30%40%50%60%70%80%90%100%
0 2 4 6 8 10 12Hospitalization Efficacy
Month
Both RSVpreF OnlyMethods: Intervention effectiveness
Example: Off -peak (Aug) birth
Additional benefit of adding nirsevimab
Note: Peak infections are typically Dec -Feb
 10
110.0%5.0%10.0%15.0%20.0%25.0%30.0%
Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb MarFraction of Annual Infections
Source: National Respiratory and Enteric Virus Surveillance System (NREVSS) (2015 -2019)Reminder: Seasonality
Results: Incremental benefit of adding
nirsevimab on top of RSVpreF
Nirsevimab given in Oct -Mar
ICER= Incremental cost effectiveness ratio ($/QALY)Birth Month $- $500,000 $1,000,000 $1,500,000 $2,000,000 $2,500,000 $3,000,000ICER ($/QALY)
12
Results: Adding nirsevimab to all
infants born to vaccinated mothers
Nirsevimab given at birth for infants born October -March, and in October/November for infants born in April through
September
13
Results: Adding nirsevimab to all
infants born to vaccinated mothers
Nirsevimab given at birth for babies born October -March, and in October/November for babies born in April through
September
14
Results: Adding nirsevimab to all
infants born to vaccinated mothers
QALYs
GainedAdditional
CostsICER
($/QALY)
0.000781 $522.12 $  668,735
Notes: Nirsevimab given at birth for babies born October -March, and in October/November for babies born in April
through September
ICER= Incremental cost effectiveness ratio; QALY= Quality -adjusted life -year
15
Results: Adding nirsevimab only for
infants born during Apr -Sept
Nirsevimab given in October/November for babies born in April through September born to mothers who received
RSVpreF
16
Nirsevimab given in October/November for babies born in April through September born to mothers who received
RSVpreFResults: Adding nirsevimab only for
infants born during Apr -Sept
17
Nirsevimab given in October/November for babies born in April through September born to mothers who received
RSVpreF
ICER= Incremental cost effectiveness ratio; QALY= Quality -adjusted life -yearQALYs
GainedAdditional
CostsICER
($/QALY)
0.001032 $502.40 $486,882 Results: Adding nirsevimab only for
infants born during Apr -Sept
18
•Marginal additional benefit beyond RSVpreF
protection
•ICER is very highSummary: Incremental benefit of
adding nirsevimab on top of RSVpreF
19
Incremental benefit of adding RSVpreF
on top of nirsevimab
20
0%20%40%60%80%100%
0 2 4 6 8 10 12 14Hospitalization Efficacy
Months since birth
RSVPreF Both NirsevimabMethods: Intervention effectiveness
21
Additional benefit of adding RSVpreF
* Assuming administration of nirsevimab at birth
0%10%20%30%40%50%60%70%80%90%100%
0 2 4 6 8 10 12Hospitalization Efficacy
Month
Both Nirsevimab OnlyMethods: Intervention effectiveness
example: Off -peak (Aug) birth
Additional benefit of adding RSVpreF
22
Results: Incremental benefit of adding
RSVpreF on top of nirsevimab
Birth Month $- $1 $2 $3 $4 $5 $6 $7 $8 $9 $10ICER ($ Millions)
ICER= Incremental cost effectiveness ratio23
•Very marginal additional benefit beyond
Nirsevimab protection
•ICERs are extremely highSummary: Incremental benefit of
adding RSVpreF on top of nirsevimab
24
•Limitation:
•No efficacy data for combination of products
•Combinations of RSVpreF and Nirsevimab add
marginal effectiveness at very high cost in the
general populationOverall summary: Combinations
25
Thank You
•Please send comments to:
•dwhutton@umich.edu
26
Appendix
27
Additional Input
Assumptions
28
Methods: Provision of Nirsevimab
•Base case:
•At birth for those born
•October 1 –March 31
•October for those born in
•April (~6 -month visit)
•June (~4 -month visit)
•August (~2 -month visit)
•November for those born in
•May (~6 -month visit)
•July (~4 -month visit)
•September (~2 -month visit)
29
Methods: Intervention effectiveness
30•Assuming Administration of Nirsevimab at birth
•MA-LRTI= medically attended lower respiratory tract infection0%20%40%60%80%100%
0 2 4 6 8 10 12 14MA-LRTI Efficacy
Months since birth
RSVPreF Nirsevimab Both
Additional combination
Results
Incremental benefit of adding on
nirsevimab top of RSVpreF
Results: Incremental benefit of adding
nirsevimab on top of RSVpreF
by month of birth
Birth Month0.0000.0100.0200.0300.0400.0500.0600.070
Outpatient ED Inpatient ICU Inpatient Day ICU DayEvents Averted per Birth
October November December January February March
April May June July August September0.0000.0010.0010.002
ICU
Nirsevimab given at birth for babies born October -March, and in October/November for babies born in April through September
Results: Incremental benefit of adding
nirsevimab on top of RSVpreF
Birth Month0100200300400500600700800900
Outpatient ED InpatientNumber Needed to Immunize to Avoid One...
November December January February March April
May June July August September01000200030004000
ICU Inpatient
DayICU Day
Nirsevimab given at birth for babies born October -March, and in October/November for babies born in April through September
Results: Incremental benefit of adding
nirsevimab on top of RSVpreF
Birth Month $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000 $500,000
Outpatient ED InpatientCost per Event Averted
October November December January February March
April May June July August September $- $500,000 $1,000,000 $1,500,000 $2,000,000 $2,500,000
ICU Inpatient
DayICU Day
Nirsevimab given at birth for babies born October -March, and in October/November for babies born in April through September
Incremental benefit of adding RSVpreF
on top of nirsevimab
00.00050.0010.00150.0020.00250.0030.00350.0040.00450.005
Outpatient ED Inpatient ICU Inpatient Day ICU DayEvents Averted per Birth
October November December January February March
April May June July August SeptemberResults: Incremental benefit of adding
RSVpreF on top of nirsevimab
Impact of adding RSVpreF in addition
to nirsevimab is bigger for births in
April -Sept since nirsevimab does not
provide protection in April -Sept for
those born in those months
Birth Month
Results: Incremental benefit of adding
RSVpreF on top of nirsevimab
Birth Month010002000300040005000600070008000900010000
Outpatient ED Inpatient ICU Inpatient Day ICU DayNumber Needed to Immunize to Avoid One...
October November December January February March
April May June July August September
Results: Incremental benefit of adding
RSVpreF on top of nirsevimab
Birth Month $- $100,000 $200,000 $300,000 $400,000 $500,000 $600,000 $700,000 $800,000 $900,000 $1,000,000
Outpatient ED Inpatient ICU Inpatient Day ICU DayCost per Event Averted
October November December January February March
April May June July August September
Results: Adding RSVpreF
What if RSV season is early?
•Scenario:
•RSVpreF provided in off -peak
•RSV season starts 2 months early
•Nirsevimab still provided in October
0.0%10.0%20.0%30.0%
Apr Jun Aug Oct Dec FebIncidence
(% of annual)Seasonality
Original Model
$6.86
$2.72
$2.25
$0.71
$1.42
$0.43
 $- $2.00 $4.00 $6.00 $8.00 $10.00ICER ($ Millions)ICER (Millions)Results: Adding RSVpreF
What if RSV season is early?
ICERs improve, but still
very expensive
Birth Month
ICER -Incremental cost -effectiveness ratio
Nirsevimab base case
update
Nirsevimab results: Base case
43•Base case:
•Population of 1,000 births
•50% uptake in the nirsevimab group
•First RSV season
•$500/dose
•Nirsevimab only impacts LRTI
LTRI= Lower respiratory tract infection
Results: Health outcomes
44Cohort:1,000 nirsevimab and 1,000 natural history, assuming 50% uptake in nirsevimab group
URTI -Upper respiratory tract infection; LRTI -Lower respiratory tract infection - 50 100 150 200 250
 Natural
History Nirsevimab  Natural
History Nirsevimab  Natural
History Nirsevimab
Medically attended
outpatientEmergency Department InpatientNumber of Events in Cohort
URTI LRTI
Results: Health outcomes
45Cohort:1,000 nirsevimab and 1,000 natural history, assuming 50% uptake in nirsevimab group29.3
10.4
3.9
0.921.1
2.6
0.05.010.015.020.025.030.035.0
Outpatient ED Inpatient ICU Inpatient Day ICU DayEvents Averted per 1000 births
Nirsevimab
Results: Health outcomes
4617 48 128 581
24 194
 - 100 200 300 400 500 600 700
Outpatient ED Inpatient ICU Inpatient Day ICU DayNumber needed to Prophylax to avoid
Nirsevimab
Results: Costs
47Base costs of nirsevimab : $500/dose, Cost of palivizumab for high -risk included in “Natural History”Cohort:1,000 births, assuming 50% uptake in nirsevimab group$0$100,000$200,000$300,000$400,000$500,000$600,000
Natural History
Nirsevimab
Natural History
Nirsevimab
Natural History
Nirsevimab
Natural History
Nirsevimab
Natural History
Nirsevimab
Natural History
Nirsevimab
Intervention Outpatient ED Inpatient Deaths TotalTotal Costs in Cohort
Medical Productivity
Results: Health outcomes
48Base costs of nirsevimab : $500/dose$3,794 $10,650 $28,372 $128,963
$5,254 $42,988
 $- $20,000 $40,000 $60,000 $80,000 $100,000 $120,000 $140,000
Outpatient ED Inpatient ICU Inpatient Day ICU DayCost per Event Averted
Nirsevimab
Results: QALYs lost
49Adverse
EventsOutpatient ED Inpatient Deaths Total Grand
Child Caregiver Child Caregiver Child Caregiver Child Child Caregiver Total
Natural
History 1.95 0.98 0.90 0.45 0.22 0.09 0.15 3.22 1.51 4.73
Nirsevimab 0.01 1.70 0.85 0.76 0.38 0.15 0.06 0.10 2.73 1.29 4.03
Cohort:1,000 births, assuming 50% uptake in nirsevimab group
Results: Cost -effectiveness
50Cohort:1,000 births, assuming 50% uptake in nirsevimab group $- $100,000 $200,000 $300,000 $400,000 $500,000 $600,000
 (4.80)  (4.60)  (4.40)  (4.20)  (4.00)  (3.80)Costs
QALYs (lost) from RSV
Natural History Nirsevimab
Base costs of nirsevimab : $500/dose, Cost of palivizumab for high -risk included in “Natural History”
Results: Cost -effectiveness
51OverallCosts ($) QALYsICER ($/QALY)
Vs. NH
Natural History 418,556 4.73
Nirsevimab 529,597 4.03 157,537
Cohort:1,000 births, assuming 50% uptake in nirsevimab group
Base costs of nirsevimab : $500/dose, Cost of palivizumab for high -risk included in “Natural History”
Sensitivity: Tornado nirsevimab
52Base cost of $500/dose$0 $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000
nirsevimab cost/dose
Disease-specific inpatient costs (per inpatient case)  Age 0-5 months
RSV QALYS Lost
Initial Efficacy
RSV-related QALYs lost Outpatient Child
Fraction Receiving Palivizumab Natural History
RSV-related QALYs lost Outpatient Child caregiver
Proportion of RSV infections with an LRTI diagnosis Outpatient Age 0-5 months
Disease-specific inpatient costs (per inpatient case)  Age 6-11 months
RSV-related QALYs lost ED  ChildIncremental Cost -Effectiveness Ratio
Low High
 $- $50,000 $100,000 $150,000 $200,000 $250,000
$0 $100 $200 $300 $400 $500 $600ICER
Total Cost of Nirsevimab (drug + administration)Sensitivity: Cost nirsevimab
53Base cost of $500/dose
Scenario: Upper respiratory infection
effect
5455.4
17.1
3.9
0.921.1
2.6
0.010.020.030.040.050.060.0
Outpatient ED Inpatient ICU Inpatient Day ICU DayEvents Averted per 1000 births
Nirsevimab
 $- $20,000 $40,000 $60,000 $80,000 $100,000 $120,000 $140,000
$0 $100 $200 $300 $400 $500 $600ICER
Total Cost of Nirsevimab (drug + administration)Scenario: Upper respiratory infection
effect
55 Nirsevimab is assumed to be equally efficacious in preventing upper respiratory tract infections as lower respiratory tract infections.
Scenario: Timing analysis
56•Cost -effectiveness of an infant receiving nirsevimab
as a newborn in
•Oct-Feb
•Oct-March
•Oct-April
•With varying efficacy in months 6 -10
•0%
•25%
•50%
Cohort:1,000 nirsevimab and 1,000 natural history, assuming 50% uptake in nirsevimab group
57Scenario: Timing and efficacy in months 6 -10
Slightly lower ICERs for Oct -MarBase cost of $500/dose
ICER= Incremental cost -effectiveness ratioCohort:1,000 nirsevimab and 1,000
natural history, assuming 50% uptake in
nirsevimab group $- $20,000 $40,000 $60,000 $80,000 $100,000 $120,000 $140,000 $160,000 $180,000
0% efficacy 25% efficacy 50% efficacyICER
Oct-Feb Oct-Mar Oct-Apr

Summary: Economics of combined use of Pfizer  maternal RSVpreF vaccine and  nirsevimab 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 MichiganPresentation to the ACIP  June 22, 2023  Research team University of Michigan •David Hutton, PhD •Lisa Prosser, PhD •Angela Rose, MPH •Kerra…