05 MacNeil Mat Peds RSV 508

U.S. Centers for Disease Control and Prevention
Evidence to Recommendation Framework :
Clesrovimab
Maternal/Pediatric RSV Work Group
Advisory Committee on Immunization Practices
June 25, 2025
1

 Policy Question
• Should clesrovimab be recommended for all infants <8 months of age born
during or entering their first RSV season?
2

    Evidence to Recommendation (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 the impact of the intervention on health equity?
3

 EtR Domain: Public Health Problem
Is RSV -associated disease among infants <8 months of age of public health
importance?
4

   RSV burden is high in children <5 years of age
Each year in the United States, RSV leads to approximately*:
~2,000,000 medical encounters1
58,000– 80,000 hospitalizations1,2,3
100– 300 deaths4,5,6
*Data on the burden of RSV disease in children under 5 are from before the 2023- 2024 RSV season, when RSV prevention products became available in the US.
References: 1) Hall et al, NEJM (2009): https://doi.org/10.1056/NEJMoa0804877 2) McLaughlin et al, J Infect Dis (2022): https://doi.org/10.1093/infdis/jiaa752 3)
CDC RSV- NET, unpublished data. 4) Thompson et al, JAMA (2003): https://doi.org/10.1001/jama.289.2.179 5) Matias et al, Influenza Other Respi Viruses (2014):
https://doi.org/10.1111/irv.12258 6) Hansen et al, JAMA Network Open (2022): https://doi.org/10.1001/jamanetworkopen.2022.0527 5
6

         RSV is the leading cause of hospitalization in infants1
In the absence of RSV prevention products:
• Most infants (68%) are infected in the
first year of life and nearly all (97%) by age 2 years
2
• 2-3% of young infants are hospitalized for
RSV3,4,5
-Highest rates occur in the first months of life,
and risk declines with increasing age in early childhood
3,5
-~80% of hospitalized children have no
underlying medical conditions3
-All infants are at risk for hospitalization
References: 1) Suh et al, JID (2022): https://doi.org/10.1093/infdis/jiac120 2) Glezen et al, Arch Dis Child (1986): https://doi.org/10.1001/archpedi.1986.02140200053026 3) Hall et al, Pediatrics (2013):
https://doi.org/10.1542/peds.2013- 0303 4) Langley et al, PIDJ (2011): https://doi.org/10.1097/INF.0b013e3182184ae7 5) Curns et al, Pediatric s (2024): https://doi.org/10.1542/peds.2023- 062574 6

   Public Health Problem -Work Group Interpretation
• Is RSV -associated disease among infants <8 months of age of public
health importance?
No Probably
No Probably
Yes Yes Varies Don’t
know
7

 EtR Domain: 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?
8

     GRADE: PICO Question
Population All infants <8 months of age born during or entering their first RSV season
Intervention Clesrovimab
Comparison No immunization
Outcomes Benefits
Prevention of:
1. RSV-associated medically attended lower respiratory tract infection (LRTI)
2. RSV-associated LRTI with hospitalization
3. RSV-associated LRTI with intensive care unit admission
4. All-cause medically attended LRTI
5. All-cause LRTI with hospitalization
Harms
1. Serious adverse events
Abbreviations: GRADE: Grading of Recommendations, Assessment, Development and Evaluation 9

     Interpreting a GRADE certainty assessment
• A certainty assessment reflects our confidence that the true effect lies close to the
estimated effect
• There are 4 certainty levels:
• High: We are very confident that the true effect lies close to that of the estimated effect. Randomized controlled
trial certainty starts here and can be downgraded or upgraded1.
• Moderate: We are moderately confident that the true effect lies close to the estimated effect, but there is a
possibility that it is substantially different.
• Low: We have limited confidence that the true effect lies close to the estimated effect; the true effect may be
substantially different from the estimated effect. Observational certainty starts here and can be downgraded or
upgraded1.
• Very low: We have very limited confidence that the true effect lies close to the estimated effect; the true effect
is likely to be substantially different from the estimated of effect.
• A certainty assessment does not reflect our confidence in the quality of the individual
st
udies or the overall confidence in benefits and harms of the vaccine, which may be
informed by additional data.
1) Evidence type may be downgraded due to risk of bias, inconsistency, indirectness, imprecision or other considerations such as publication bias and upgraded for indications of a dose -response
gradient, large or very large magnitude of effect, and opposing residual confounding.
Abbreviations: GRADE: Grading of Recommendations, Assessment, Development and Evaluation 10

    GRADE: Outcomes, importance, and data sources
Outcome Importance1 Data sources
Benefits
1. RSV -associated medically attended LRTI Critical Phase 2b/3 RCT2
2. RSV -associated LRTI with hospitalization Critical Phase 2b/3 RCT2
3. RSV -associated LRTI with ICU admission Critical Phase 2b/3 RCT2
4. All -cause medically attended LRTI Important Phase 2b/3 RCT2
5. All -cause LRTI with hospitalization Important Phase 2b/3 RCT2
Harms
6. Serious adv
erse events Importan
t Phase 2b/3
RCT2
1. Three options: Critical; Important but not critical; Not important for decision making
2. Protocol 004: A Phase 2b/3 Double -Blind, Randomized, Placebo- Controlled Study to Evaluate the Efficacy and Safety of Clesrovimab in Healthy
Preterm and Full -Term Infants – described in Zar et al., Open Forum Infectious Diseases (2025): https://doi.org/10.1093/ofid/ofae631.003 ; Sinha,
presentation to ACIP (2024): https://www.cdc.gov/acip/downloads/slides -2024- 10-23-24/02- RSV-Mat-Peds -Sinha -508.pdf ; and unpublished data
from manufacturer Abbreviations: GRADE: Grading of Recommendations, Assessment, Development and Evaluation | LRTI: Lower respiratory tract infection |
RCT: randomized controlled trial | ICU: intensive care unit
11
GRADE Benefits : Efficacy estimates and concerns in
Outcome Efficacy estimate1
% (95% CI) Concerns in certainty assessment
1. RSV -associated medically attended LRTI 60.4 (44.1, 71.9) Not serious (indirectness)2
2. RSV -associated LRTI with
hospitalization 90.9 (76.2, 96.5) Not serious (indirectness)2
3. RSV LRTI with ICU admission3 100.0 (24.0, 100.0) Serious (imprecision)4
Not serious (indirectness)2
4. All -cause medically attended LRTI 13.1 ( -0.6, 24.8) Serious (imprecision)5
Not serious (indirectness)2

     certainty assessment
Benefits, through 150 days of follow- up
5. All-cau
se LRTI with hospitalization 49.0 (26.7,
64.5) Not ser
ious (indirectness)2
1. Esti
mates and 95% CI were estimated from the modified Poisson regression with robust variance method.
2. Concern for indirectness: the trial excluded infants who were palivizumab -eligible and took place during a season with disrup ted seasonality due to COVID -19. This was
deemed not serious.
3. Outcome was not a trial endpoint and was assessed post- hoc.
4. Serious concern for imprecision: the number of study participants did not meet optimal information size.
5. Serious concern for imprecision: the confidence interval containing estimates for which different policy decisions might be considered.
Abbreviations: GRADE: Grading of Recommendations, Assessment, Development and Evaluation | CI: confidence interval | LRTI: lower respiratory tract infection | RCT:
randomized controlled trial | ICU: intensive care unit 12

      GRADE Harms : Relative risk of serious adverse events
(SAEs) and concerns in certainty assessment, days 1 -
365 post immunization
Outcome Relative risk1 (95% CI) Concerns in certainty assessment
Harms
Seri
ous adverse events (SAEs)2 0.93 (0.77, 1.12) Ser ious (imprecision)3
1. Relative risk was calculated as the risk of a serious adverse event in the clesrovimab arm divided by the risk of a serious adverse
event in the placebo arm.
2. Adverse event resulting in death, hospitalization, significant disability, or requiring medical intervention. Serious adverse ev ents
may be related or unrelated to the study intervention.
3. Serious concern for imprecision: too few infants were included in the trial to capture rare events.
Abbreviations: GRADE: Grading of Recommendations, Assessment, Development and Evaluation | CI: confidence interval 13

   Summary of GRADE for clesrovimab
Outcome Importance Design
(# of studies) Findings Evidence type
Benefits
1. RSV -associated
medically attended LRTI Critical RCT (1) Clesrovimab is effective in preventing RSV -associated
medically attended LRTI High
2. RSV -associated LRTI
with hospitalization Critical RCT (1) Clesrovimab is effective in preventing RSV -associated LRTI
with hospitalization High
3. RSV -associated LRTI
with ICU admission Critical RCT (1) Clesrovimab is effective in preventing LRTI with ICU
admission Moderate
4. All -cause medically
attended LRTI Important RCT (1) Clesrovimab is not effective in preventing all cause medically attended LRTI Moderate
5. All -cause LRTI with
hospitalization Important RCT (1) Clesrovimab is moderately effective in preventing all cause hospitalization with LRTI High
Harms
6. Serious adverse events Important RCT (1) Serious adverse events were balanced between the
clesrovimab group and the placebo group Moderate
Abbreviations: LRTI: Lower respiratory tract infection | RCT: randomized control trial | ICU: intensive care unit | serious adverse events 14

   Additional benefits of clesrovimab not included in GRADE:
Efficacy for RSV -associated medically -attended LRTI and
hospitalization observed through 180 days
Outcome Follow- up time: 150 days Follow- up time: 180 days
Events/
Clesrovimab (n/N) Events/ Placebo (n/N) Efficacy estimate % (95% CI) Events/ Clesrovimab (n/N) Events/ Placebo (n/N) Efficacy estimate % (95% CI)
RSV-associated
medically attended LRTI 60/2398 74/1201 60.4 (44.1, 71.9) 64/2398 77/1201 59.5 (43.3, 71.1)
RSV-associated LRTI with
hospitalization 5/2398 27/1201 90.9 (76.2, 96.5) 5/2398 28/1201 91.2 (77.2, 96.6)
Abbreviations: LRTI: lower respiratory tract infection | CI: confidence interval 15

   Additional benefits of clesrovimab not included in
GRADE
• If recommended by CDC, there will be two approved1 and recommended2
long-acting monoclonal antibodies for prevention of severe RSV disease in
infants
• Multiple products with different binding sites are beneficial if resistance
mutations develop to either product
• Multi
ple manufacturers in the same market allow for:
-If one product has insufficient supply in the United States, the other product
re
duces the risk of a shortage.3
-Competitive pricing of products may be created by market competition
1. In July 2023, the Food and Drug Administration (FDA) approved nirsevimab for the prevention of RSV –associated lower respirato ry tract infection among infants and children aged <24
months. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761328s000lbl.pdf and 2. In August 2023, the Advisory Committee for Immunization Practices recommended
nirsevimab infants aged <8 months born during or entering their first RSV season and for infants and children aged 8 –19 months who are at i ncreased risk of severe RSV disease entering
their second RSV season. https://www.cdc.gov/mmwr/volumes/72/wr/mm7234a4.htm ; 3. https://www.cdc.gov/han/2023/han00499.html 16

     Additional harms of clesrovimab not included in
GRADE: Solicited adverse events (AEs), days 1 –5 post
immunization
• Injection -site and systemic reactions were comparable between the
clesrovimab (29.9%) and placebo (30.9%) arms
-Irritability and somnolence were the most commonly reported solicited AEs
• Mostly Grade 1 (mild) or 2 (moderate)
-The proportions of participants with solicited AEs of Grade 3 (severe) were low
(≤
0.2%) in both groups
-No Grade 4 (potentially life -threatening) solicited AEs
Notes: Grade 1= mild; Grade 2= moderate; Grade 3=severe; Grade 4=potentially life threatening; https://www.fda.gov/media/73679/download 17

 Additional potential harms of clesrovimab not
included in GRADE: Fever*, days 1 –5 post
immunization
• Rates of fever were comparable between the clesrovimab (3.7%) and
placebo (4.0%) arms
Study Events*/Clesrovimab Events*/Placebo
(n/N) (n/N)
Protocol 004 89/2408† (3.7%) 48/1202 (4.0%)
*Fever defined as a temperature ≥ 100.4 °F
† Total N=2409; 2408 had temperature data available per communication with manufacturer on March 9, 2025
18

       Work group interpretation of benefits and harms of
clesrovimab
Benefits
• Efficacious long -acting, monoclonal antibody that can prevent severe RSV
disease in young infants during the duration of their first RSV season
• Second long -acting, monoclonal antibody RSV prevention product would
mitigate the risk of manufacturing shortages and loss of efficacy due to
mutations in the binding site.
Harms
• Favorable safety profile with no observed increase in serious adverse events,
local or systemic reactions, including fever
• Rare serious adverse events unlikely to be detected in a trial due to sample
size
19

   Benefits and Harms
• How substantial are the desirable anticipated effects?
-How substantial are the anticipated effects for each main outcome for
which there is a desirable effect?
Minimal Small Moderate Large Varies Don’t know
20

   Benefits and Harms
• How substantial are the undesirable anticipated effects?
-How substantial are the anticipated effects for each main outcome for
which there is an undesirable effect?
Minimal Small Moderate Large Varies Don’t know
21

 Benefits and Harms
• Do the desirable effects outweigh the undesirable effects?
Favors intervention (clesrovimab)
Probably favors the intervention (clesrovimab)
Probably favors the comparison (no
immunization)
Favors the comparison (no immunization)
Unclear
22

  EtR Domain: Values
Do parents and caregivers feel that the desirable effects of clesrovimab are large
relative to the undesirable effects?
Is there important uncertainty about, or variability in, how much parents and
caregivers value the prevention of severe RSV disease?
23

    RSV risk perceptions and knowledge among pregnant
women in the U.S. (n=523), December 2022- January 2023
In a nationwide, online survey of women who were pregnant or < 12 months
postpartum:
• 31% of respondents reported knowing a baby who had been hospitalized for
RSV
• 40% of respondents believed that their own baby would be moderately or
severely ill if infected with RSV
• 69% of respondents were worried their baby would need to be hospitalized if infected with RSV
Reference: Gidengil et al, Open Forum Infect Dis. (2023): https://doi.org/10.1093/ofid/ofad500.1467 24

  Parents do not have a clear preference among RSV
immunization products
Parental preference for RSV immunization products if both were available, safe and effective
among adults aged 18-49 years with children, CASCADIA Study, Oregon and Washington, U.S.,
April-May 2023 (n=1082)
37%
12%
3% 48% Maternal RSV vaccine
Long-acting monoclonal antibody
Neither No preference
Source: Kuntz et al. Attitudes about Respiratory Syncytial Virus (RSV) Vaccination during Pregnancy, and Infant Monoclonal Antibodies for RSV, 2024 25
– - -

  50% of women 18-49 years who have an infant <8 months
received a long -acting monoclonal antibody
Infant protection against RSV by maternal RSV vaccination* or receipt of nirsevimab †, and
intent ‡ for nirsevimab receipt by women aged 18– 49 years who have an infant <8 months
during the RSV season (born since April 1, 2024), February 2025, United States
Mother received RSV vaccination
during pregnancy
Infant received nirsevimab
Definitely will get nirsevimab for
infant
Probably will get nirsevimab for
infant or unsure
Probably or definitely will not get
nirsevimab for infant
*Receipt of RSV vaccination during pregnancy was assessed by the NIS –ACM questionnaire among women 18 –49 years who reported having an infant born since October 1, 2024. For infants born April 1, 2024, through September 30, 2024, maternal RSV
vaccination was not assessed, and these infants were assumed to be protected against RSV only if infant was reported to have received nirsevimab. The estimates of receipt of RSV vaccination during pregnancy for infants born since April 1, 2024 are not a n
assessment of maternal RSV vaccination coverage among pregnant women eligible for vaccination as shown with the Vaccine Safety Datalink , as they are based on all infants eligible for nirsevimab or maternal vaccination rather than eligible pregnancies
†Estimates of nirsevimab receipt by infants born since April 1, 2024, include those who were born shortly before or are enter ing their first RSV season and do not account for the mother's RSV vaccination status during pregnancy
‡Intent for nirsevimab receipt is assessed among infants who had not received nirsevimab and whose mother did not receive RSV vaccination during pregnancy. Estimates of nirsevimab intent among women interviewed in August and September 2024
included all women who reported having an infant <8 months, and could include infants born in February and March 2024.
Data Source: National Immunization Survey Adult COVID Module https://www.cdc.gov/rsvvaxview/dashboard/nirsevimab coverage infants.html 26

  Values
• Do parents and caregivers feel that the desirable effects of clesrovimab
are large relative to the undesirable effects?
No Probably
No Probably
Yes Yes Varies Don’t
know
Majority opinion Minority opinion 27

  Values
• Is there important uncertainty about, or variability in, how much
parents and caregivers value the prevention of severe RSV disease?
Important uncertainty or variability
P
robably important uncertainty or variability
P
robably not important uncertainty or variability
N
o important uncertainty or variability
N
o known undesirable outcomes
Majority opinion Minority opinion
28

   EtR Domain: Acceptability
Is clesrovimab acceptable to key stakeholders?
29

        Pediatrician attitudes regarding long -acting
monoclonal antibody
Pediatrician attitudes about nirsevimab, Pediatrician survey*, October 2024, n=200
91 94.5
7 95.5 96.5
4
4.5 3 0.5
Nirsevimab is safe for infants
0.5
Nirsevimab is effective against severe RSV disease in infants
Strongly agree or agree
1 Neither agree nor disagree
I feel confident discussing and recommending nirsevimab Disagree or strongly disagree immunization with my patient's parents/caregivers
2
I feel comfortable co-administering nirsevimab and one or more
vaccines to my pediatric patients in one visit.
0% 20% 40% 60% 80% 100%
• 77% of pediatricians reported that their practice had ever offered nirsevimab
• The majority of pediatricians agreed that nirsevimab is safe for infants and effective against severe
disease in infants
*Porter Novelli View Points Health Care Practitioner survey was conducted from October 2 -10, 2024, among 200 U.S. pediatricians who reported of fering at least some routine pediatric vaccines
to patients 30
Reference : Kang et al, CDC (2024); https://www.cdc.gov/rsvvaxview/publications/rsv -immunization -survey -2024.html

  RSV prevention through long -acting, monoclonal
antibodies endorsed by national organizations
• N irsevimab is recommended by
-American Academy of Pediatrics1
-American Academy of Family Physicians2
-National Foundation for Infectious Diseases3
1) https://publications.aap.org/redbook/resources/25379/AAP -Recommendations -for-the-Prevention -of-RSV?autologincheck=redirected
2) https://www.aafp.org/news/health -of-the-public/rsv -antibody -aafp- approval.html
3) https://www.nfid.org/resource/contagious- chronicles -updated- recommendations -for-respiratory- season/ 31

  Acceptability
• Is clesrovimab acceptable to key stakeholders?
No Probably
No Probably
Yes Yes Varies Don’t know
Majority opinion Minority opinion 32

  EtR Domain: Feasibility
Is clesrovimab feasible to implement among all infants <8 months of age
born during or entering their first RSV season?
33

   Implementation and access
• The Vaccines for Children (VFC) program is a federally -funded program that
provides immunizations at no cost to children who might not otherwise be
immunized because of inability to pay.1
-If ACIP votes to include clesrovimab in VFC, it will be the second monoclonal
antibody to be included in the VFC program.
• I mplementation pros and cons:
-Pro: Clesrovimab is a single dose regardless of weight
-Con: Stocking clesrovimab may be challenging for providers who also need to
stock nirsevimab for high -risk children 8 through 19 months entering their second
RSV season and prefer to stock a single RSV monoclonal antibody
1. CDC. Vaccines for Children . https://www.cdc.gov/vaccines -for-children/about/index.html 34
7.8 10.9 13 23.9 2020.1 19.6 21.4 28.6 30.5 27.9 39.1 30.5 26 45.7 38.3 4447.4

  Frequency of main challenges* pediatricians reported or
anticipated in offering long-acting monoclonal antibody,
Pediatrician survey, October 2024 (n=200)
Parent/caregiver concerns around nirsevimab safety 32.6
33.5 Challenges knowing maternal RSV vaccination status to determine infant eligibility 17.4
Financial burden in purchasing of nirsevimab**
Challenges with reimbursement from private health insurance plans
24.5 Lack of demand from parents/caregivers 10.9
20Challenges deterimining infant eligibility*** 15.2
Parent/caregiver concerns around nirsevimab effectiveness
15.5 Challenges with Medicaid reimbursement
7.5 7.8 6.5 Supply/stock issues
8.5 Practice  does not ha  ve or does not anticipate having  challenges in o  ffering nirsevimab
All pediatricians (n=200) Pediatricians whose practice had ever offered nirsevimab (n=154) Pediatricians whose practice had never offered nirsevimab (n=46)
*R
espondents were instructed to select up to 3 response categories
** Private stock of nirsevimab for practices participating in the VFC (Vaccines for Children) program
*** Challenges knowing whether infant received nirsevimab at a birthing hospital Kang et al , https://www.cdc.gov/rsvvaxview/publications/rsv -immunization -survey -2024.html 35

  Feasibility
• Is clesrovimab feasible to implement among all infants <8 months of
age born during or entering their first RSV season?
No Probably
No Probably
Yes Yes Varies Don’t know
Majority opinion Minority opinion
36

    EtR Domain: Resource Use
Is clesrovimab a reasonable and efficient allocation of resources?
37

  RSV-associated outcomes averted: 50% coverage with
clesrovimab among an annual US birth cohort1
Comparison Outpatient
Visits Averted ED Visits Averted Hospital Admissions Averted ICU Admissions Averted Deaths Averted QALYs Gained
Clesrovimab
2 vs. no RSV
immunizations for most
infants3 121,022 43,480 20,198 4,444 20 3,413
1. Estimates provided by an updated UM- CDC model, where updates included VE and cost/dose. Original model and methods described her e: Hutton et al, Pediatrics (2024):
https://doi.org/10.1542/peds.2024- 066461
2. Clesrovimab has 50% coverage, and includes 50% palivizumab use for eligible high -risk babies that do not get clesrovimab
3. “No RSV immunizations for most infants " means the only RSV immunization is palivizumab for eligible high -risk infants
Abbreviations: ED: emergency department | ICU: intensive care unit | QALY: quality adjusted life year 38

          Incremental cost effectiveness ratios (ICERs): 50%
coverage with clesrovimab among an annual US birth
cohort1
Comparison $/Outpatient
Visit Averted $/ED Visit Averted $/Hospital Admission Averted $/ICU Admission Averted $/Death Averted $/QALY Gained
Clesrovimab
2 vs. no
RSV i mmunizations for
most infants3 2,948 8,207 17,666 80,300 17,666,032 104,543
1. Estimates provided by an updated UM- CDC model, where updates included vaccine efficacy, vaccine efficacy waning trajectory, and cost/dose. Original model and methods described here:
Hutton et al, Pediatrics (2024): https://doi.org/10.1542/peds.2024- 066461
2. Clesrovimab has 50% coverage, and includes 50% palivizumab use for eligible high -risk babies that do not get clesrovimab
3. “No RSV immunizations for most infants " means the only RSV immunization is palivizumab for eligible high -risk infants
Abbreviations: ED: emergency department | ICU: intensive care unit | QALY: quality adjusted life year 39

  Incremental Cost -Effectiveness Ratio ($/QALY gained)
$0 $50,000 $100,000 $150,000 $200,000 $250,000
Disease-Specific Inpatient Costs (per Inpatient Case)
RSV QALYS Lost
Clesrovimab cost/dose
Proportion of Outpatient Visits With an LRTI Diagnosis Age 0-5 Months
Proportion of Hospitalizations With an LRTI Diagnosis Age 0-5 Months
Proportion of Outpatient Visits With an LRTI Diagnosis Age 6-11 Months
Fraction Receiving Palivizumab Natural History
Outpatient Efficacy
RSV Mortality Per Hospitalization Age 0-5 Months
Efficacy 6-10 months
Low High Base case: ~$105,000 $/QALY gained

      One -way sensitivity analysis: 50% coverage with
clesrovimab among an annual US birth cohort1
1. Estimates provided by an updated UM- CDC model, where updates included VE and cost/dose. Original model and methods described her e: Hutton et al, Pediatrics (2024):
https://doi.org/10.1542/peds.2024- 066461
Abbreviations: QALY : quality adjusted life year | LRTI: lower respiratory tract infection 40

    Resource Use
• Is clesrovimab use among infants under 8 months of age born during or
entering their first RSV season a reasonable and efficient allocation of
resources with an estimated cost of $458 on average ($365 VFC / $560
other) per dose?
No Probably
No Probably
Yes Yes Varies Don’t know
Majority opinion Minority opinion
Abbreviations: VFC: Vaccines for Children 41
 EtR Summary
42

     Work group considerations and interpretation
• Phase 2b/3 trial demonstrated high efficacy for prevention of severe RSV disease
through 150 days
• Serious adverse events appeared balanced between the clesrovimab and placebo
arms; however, rare adverse events are unlikely to be detected in a trial of this
size
• Work group discussion also highlighted:
• Clesrovimab has demonstrated a shorter half- life than nirsevimab (44 days1 vs 71 days2)
though efficacy against severe RSV appeared sustained through 150 days
• Clesrovimab and nirsevimab trial outcomes had different definitions , making direct comparisons in
efficacy challenging
References 1) FDA prescribing information for clesrovimab: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761432s000lbl.pdf 2) FDA prescribing information for
Nirsevimab: ihttps://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761328s000lbl.pdf 43

     Work group considerations and interpretation,
continued
• The work group highlighted the benefits of multiple long -acting RSV
antibody products and multiple manufacturers, including:
-If RSV develops resistance to one product or one product has insufficient supply,
another is available
-Potential for decrease in price
• T he leading cause of hospitalization in infants (RSV) can be prevented
through immunization. However, for RSV immunizations to have public
health impact, they must be administered early:
-For infants born o utside the  RSV season, high uptake prior to season onset is
critical
-For infants born dur
ing the
 RSV season, administration should be within the first
week of life -ideally during the birth hospitalization
44

    Evidence to Recommendations Framework
Summary
• What is the balance between the desirable effects relative to the undesirable effects?
Balance of
consequences Undesirable
consequences
clearly
outweigh
desirable
consequences
in most settings Undesirable
consequences
probably
outweigh
desirable
consequences
in most settings The balance
between
desirable
and undesirable
consequences
is closely
balanced or
uncertain Desirable
consequences
probably
outweigh
undesirable
consequences
in most settings Desirable
consequences
clearly
outweigh
undesirable
consequences
in most settings There
is insufficient
evidence
to determine
the balance of
consequences
45

 Evidence to Recommendations Framework
Summary
• Should clesrovimab be recommended for all infants <8 months of age born during or
entering their first RSV season?
Type of
recommendation We do not
recommend the
intervention We recommend
the intervention for
individuals based on
shared
clinical decision -
making We recommend
the intervention
46

 Acknowledgements
Maternal/Pediatric RSV Work Group
Coronavirus and Other Respiratory Viruses Division Immunization Services Division RSV-NET
NIS- ACM
47

     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.
48

Back -up
49

  RSV-associated hospitalization rates are highest in
infants less than 8 months
Rate of RSV -associated hospitalization by month of life among children age <2 years, December 2016 –September 2020,
40 New Vaccine Surveillance Network (NVSN)
31.2 35
30 25 20 15 10
5 0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 <24
Month of Life 17.7 22.4
15.7
13.7
11.0
9.6
8.0
7.4 8.8
6.0 6.0 6.3
5.0 5.8 5.4
4.0 3.7 3.7 3.4 2.8 2.1 1.8 2.9 8.5 Hospitalization Rate per 1,000 Children
Reference: Curns et al, Pediatric s (2024): https://doi.org/10.1542/peds.2023- 062574 50
2024–2025 RSV seasonality has returned to pre-
pandemic trends
Percentage* of polymerase chain reaction (PCR) test results positive for respiratory syncytial
virus (RSV)**, by epidemiologic week — National Respiratory and Enteric Virus Surveillance
System, United States, July 2009– June 2025
Pre-COVID -19
pandemic
seasonality
(2009-2019)
shown by grey
shaded area

Notes: Report was last updated on 6/17/2025.
*All results presented are from polymerase chain reaction (PCR) tests, which represent >90% of the diagnostic tests reported to NREVSS. The last three weeks of data in 2024 -25 may be less complete. NREVSS is an abbreviation for the National Respiratory
and Enteric Virus Surveillance System. For more information on NREVSS, please visit National Respiratory and Enteric Virus Surveillance System | CDC .
**Respiratory syncytial virus types A and B are not shown separately in this report.
***The NREVSS surveillance season runs from the first week in July through June of the following year.
Abbreviations: %+: percent positive 51

Summary: U.S. Centers for Disease Control and Prevention  Evidence to Recommendation Framework :  Clesrovimab  Maternal/Pediatric RSV Work Group   Advisory Committee on Immunization Practices  June 25, 2025  1         Policy Question  • Should clesrovimab be recommended for all infants <8 months of age born during or entering their first RSV season?  2                                                            Evidence to Recommendation (EtR ) Framework  EtR Domain Question(s)  Public Health Problem…


06 MacNeil Mat Peds RSV 508

Work group considerations and
clinical considerations for clesrovimab
Maternal and Pediatric RSV Session
Coronavirus and Other Respiratory Viruses Division
June 25, 2025U.S. Centers for Disease Control and Prevention

•Work group considerations and interpretations of uptake, safety,
effectiveness, and impact studies
•Review of clinical considerations
-Clesrovimab recommendations compared with nirsevimab
-Clesrovimab storage, handling, and administrationOutline
2
•Nirsevimab was effective against RSV -associated emergency
department encounters, hospitalization, and critical illness among infants in
their first RSV season
•Maternal vaccination was effective against RSV -associated ED encounters
and hospitalizations
•An estimated 57% of infants were either born to vaccinated mother
orreceived nirsevimab
•Compared with prior to RSV immunization introduction, RSV -associated
hospitalization rates were reduced by ~30 –40% among eligible infants and
by half among infants aged 0 –2 monthsSummary of RSV immunization effectiveness, uptake,
and impact for the 2024 -25 RSV season
3
•The impact of RSV immunizations to decrease severe RSV disease in infants
during the 2024 –25 RSV season in the RSV -NET and NVSN networks is clear1
•Increasing uptake is important in order to  further reduce burden of RSV
disease
-Higher impact has been seen in other countries that have attained higher uptake
of these immunizations2–6
-Important to maximize availability of RSV immunizations, including providing
infant RSV antibody during birth hospitalization
-The increase in birthing hospital enrolled in the Vaccine For Children (VFC)
program is important, but challenges remain
 Workgroup considerations on RSV immunization
effectiveness, uptake, and impact
RSV-NET RSV -Associated Hospitalization Surveillance Network; NVSN: New Vaccine Surveillance Network
1Patton 2025 MMWR 2 Bloomfield 2025 Medical Journal of Australia ;3Dessers 2025 Belgian Journal of Paediatrics ; 4García‐García 2025 Influenza and Other Respiratory Viruses ; 5Ares -Gomez 2024
Lancet ID ; 6Mazagatos 2024 Influenza Other Respir Viruses ; 4
•During the reporting period since approval until March 31, 2025, the most
frequently reported adverse events involved patients who developed RSV
infections despite prior receipt of nirsevimab, and included signs,
symptoms, or complications of these infections (e.g., bronchiolitis).
•No product safety labeling updates have been made since serious
hypersensitivity reactions with nirsevimab were added on February 23,
2024.
•No additional safety signals have been identified at this time.
•Errors involving incorrect nirsevimab dose or incorrect product (e.g., adult
vaccine being given to infant) continue to be reported.
•FDA will continue routine pharmacovigilance for nirsevimab. Summary of FAERS1 postmarketing  adverse events and
medication errors reporting with nirsevimab
1FDA Adverse Event Reporting System (FAERS) Database | FDA 5
•Study of 37,909 infants that received nirsevimab  during 2024 -2025 season
using self -controlled risk interval
•No increased risk observed for seizures, immune thrombocytopenia (ITP),
drug reactions, sepsis, or fever
•No cases of anaphylaxis and 18 (~0.05% of doses) cases of allergic reaction
reported, primarily hivesSummary interpretation of Vaccine Safety Datalink
nirsevimab study
6
•FAERS and VSD safety data are reassuring
•Continued monitoring of safety importantWorkgroup interpretation of nirsevimab safety
FAERS: FDA Adverse Event Reporting System; VSD: Vaccine Safety Datalink; CSF: cerebrospinal fluid 7
•Matched cohort with ~14,000 pairs of vaccinated -unvaccinated pregnant
women
•No increased risk observed for most outcomes, including fever, fatigue,
stroke, seizure, Bell’s palsy, ITP , pulmonary embolism, preterm birth, infant
being born small for gestational age, stillbirth
•Association of maternal RSV vaccine and HDP overall (adjusted odds ratio
[aOR]: 1.09 [95% CI, 1.03 –1.15]) and preeclampsia ( aOR: 1.12 [95% CI,
1.03 –1.21])
-Severity of HDP similar among vaccinated and unvaccinated
-Potential residual confounding (e.g., including parity in the propensity matching)
and outcome misclassification due the difficulty in determining the timing of
when HDP first occurs and lack of chart reviewVaccine Safety Datalink maternal vaccine study
summary
ITP: Immune Thrombocytopenic Purpura; HDP: hypertensive disorders of pregnancy 8
•Overall study findings were reassuring, including lack of association of
preterm birth and vaccination
•WG continues to feel that the benefits of maternal RSV vaccination clearly
outweigh the potential risks
•WG was split on importance of the association of vaccination and HDP
-Some were concerned that an imbalance of HDP was seen in multiple studies
(phase 3 clinical trial, published retrospective cohort study, postmarketing  study),
and felt it was important that healthcare providers discuss the potential risk of
HDP with pregnant women
-Some were not concerned about this association since the effect size was small,
and there was no increased severity in vaccinated vs. unvaccinated women with
HDP and no overall association of vaccination with preterm birth; American
College of Obstetricians and Gynecologists was in agreement  with this opinionWork group interpretation of maternal vaccine
Vaccine  Safety Datalink study findings
9 HDP: hypertensive disorders of pregnancy
•Long -acting, monoclonal antibody manufactured by Merck
•Passive immunization
•Single -dose, manufacturer -filled syringe
-105 mg/0.7 mL
-Same dose for all infants regardless of weightInfant RSV Antibody –Clesrovimab

•Clesrovimab  and nirsevimab  recommendations would be the same for use
in infants younger than 8 months of age born during or entering their first
RSV season
-No preferential recommendation for use of clesrovimab  versus nirsevimab
•Only  nirsevimab1 recommended for children ages 8 through 19 months
who are at increased risk of severe RSV disease and entering their second
RSV season
-Infants eligible to receive nirsevimab  when entering second RSV season could
have received nirsevimab  or clesrovimab  for first RSV season
-No effectiveness or safety concerns for using clesrovimab  for first RSV season and
nirsevimab  for second RSV seasonProposed use of clesrovimab versus nirsevimab
1  Clesrovimab not recommended for this age group because it is not approved by FDA for this indication 11
•One dose for infants younger than 8
months of age born during or
entering their first RSV season
(administration during October through
March in most of the continental U.S.) if:
-The mother did not receive RSV vaccine
during pregnancy
-The mother’s RSV vaccination status is
unknown
-The infant was born less than 14 days after
maternal RSV vaccination
Use of Nirsevimab for the Prevention of Respiratory Syncytial Virus Disease Among Infants and Young Children:
Recommendations of the Advisory Committee on Immunization Practices — United States, 2023 | MMWR 12
Proposed recommendations for use
ofRSV antibody immunizations
(nirsevimab or clesrovimab) in infants
< 8 months
•Born to mothers who may not mount an adequate immune response to
vaccination (e.g., immunocompromising conditions)
•Born to mothers who have conditions associated with reduced
transplacental antibody transfer (e.g., living with HIV infection)
•Infants who have procedures leading to loss of maternal antibodies (e.g.,
cardiopulmonary bypass, extracorporeal membrane oxygenation [ECMO],
exchange transfusion)
•Infants with substantially increased risk for severe RSV disease
(e.g., hemodynamically significant congenital heart disease, ICU admission
with oxygen requirement at discharge) When RSV antibody may be considered for
infants born to vaccinated mothers1
RSV Immunization Guidance for Infants and Young Children | RSV | CDC  | ICU: intensive care unit;  1 For infants aged <8 months during their first RSV season

Choose one product to prevent severe RSV disease in infants
Most infants will not need both maternal vaccination and an RSV antibody.
Maternal RSV vaccination
- Pfizer AbrysvoInfant RSV antibody
-Nirsevimab
-Clesrovimab- or -
Infant RSV antibody and maternal vaccination have
different administration windows to provide optimal
protection to the infant
Optimal timing for infant RSV administration is shortly before the RSV season
Administration should be targeted shortly before the start of their first RSV season and continued during the
season for those who have not received a dose
Forinfants born shortly before or during the RSV season , immunize within 1 week of birth, ideally during the birth
hospitalization
RSV seasonality differs based on climate
RSV Immunization Guidance for Infants and Young Children | RSV | CDC
Use of Nirsevimab for the Prevention of Respiratory Syncytial Virus Disease Among Infants and Young Children: Recommendations  of the Advisory Committee on Immunization Practices — United
States, 2023 | MMWR
In jurisdictions with differing RSV seasonality (e.g., Alaska, southern Florida,
Puerto Rico, and other jurisdictions with tropical climates), providers should
follow state, local, or territorial guidance on the timing of administration.
Administer the correct RSV immunization product
Infant RSV
antibody* onlyInfants and Some
Young Children
Abrysvo  (Pfizer)
onlyDuring Pregnancy
 Older Adults
Do not administer
RSV antibody*, Arexvy ,
or mResvia  during
pregnancy.Do not administer
Abrysvo, Arexvy , or
mResvia  to infants or
children.Abrysvo  (Pfizer )
 Arexvy  (GSK)
 mResvia  (Moderna )
Do not administer RSV
antibody* to older adults.
*Includes nirsevimab, clesrovimab, and palivizumab.
Clesrovimab (or nirsevimab) and palivizumab
•If clesrovimab or nirsevimab is
given to an infant or child… …then do not give palivizumab
during the same RSV season.
Use of Nirsevimab  for the Prevention of Respiratory Syncytial Virus Disease Among Infants and Young Children: Recommendations of the Advisory C ommittee on Immunization Practices — United
States, 2023 | MMWR , AAP Recommendations for the Prevention of RSV Disease in Infants and Children | Red Book Online | American Academy of Pediatr ics
Clesrovimab*
or nirsevimabPalivizumab

Infant RSV antibody administration
Beyfortus Prescribing Information (fda.gov)  Enflonsia Prescribing Information.pdf•Route
-Intramuscular injection
•Site
-Vastus lateralis muscle of anterolateral thigh
-The gluteal muscle should not be used.
•Coadministration
-Simultaneous administration with vaccines is
acceptable.

Clesrovimab storage and handling
Store refrigerated between 2 °C and 8 °C (36°F and 46 °F).
Use within 48 hours of removing from refrigerator.
-May be kept at room temperature, between 20 °C and
25°C (68°F and 77°F), for a maximum of 48 hours
Do not freeze.
Protect from light.Do not shake.
Enflonsia Prescribing Information.pdf
•If RSV antibody is administered alone:
-Report suspected adverse events (AEs) to MedWatch
-www.fda.gov/medwatch
•If RSV antibody is administered simultaneously with any
vaccine:
-Report suspected AEs to Vaccine Adverse Event Reporting System
(VAERS)
-vaers.hhs.gov
-Additional reporting to MedWatch is not necessaryHow to report adverse events after infant RSV
antibody administration
RSV Immunization Guidance for Infants and Young Children | RSV | CDC

For more information, contact CDC
1-800-CDC-INFO (232 -4636)
TTY:  1 -888-232-6348    www.cdc.gov
The findings and conclusions in this report are those of the
authors and do not necessarily represent the official
position of the Centers for Disease Control and Prevention.

Summary: Work group considerations and  clinical considerations for clesrovimab Maternal and Pediatric RSV Session Coronavirus and Other Respiratory Viruses Division June 25, 2025U.S. Centers for Disease Control and Prevention  •Work group considerations and interpretations of uptake, safety,  effectiveness, and impact studies •Review of clinical considerations -Clesrovimab recommendations compared with nirsevimab -Clesrovimab storage, handling, and administrationOutline 2 •Nirsevimab was effective…


01 dugan influenza 508

U.S. Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation
use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.
Influenza Session —Introduction
Dr. Vivien Dugan
Influenza Division, CDC/NCIRD
June 26, 2025
Flublok (recombinant influenza vaccine) in older children and
adolescents: immunogenicity and safety
–Dr. Pedro Folegatti (Sanofi Pasteur)
Estimates of influenza burden and burden averted through vaccination
–Dr. Vivien Dugan (CDC/NCIRD)
2024 -25 influenza season update and seasonal influenza vaccine
recommendations for the 2025 -26 U.S. influenza season
–Dr. Vivien Dugan (CDC/NCIRD)Session Overview
2

Summary: U.S. Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Influenza Session —Introduction Dr. Vivien Dugan Influenza Division, CDC/NCIRD June 26, 2025 Flublok (recombinant influenza vaccine) in older children and …


02 folegatti influenza 508

VAP00027
Immunogenicity and Safety of Quadrivalent Recombinant
Influenza Vaccine (RIV4) in Children and Adolescents
Aged 9 to 17 Years and Adults Aged 18 to 49 Years
For the Advisory Committee of Immunization Practices (ACIP) Influenza Working Group
MAT-US-2504669 P v3.0 EXP 28 APR 2026Pedro Folegatti   – Global Clinical Development Director (Presenter)
Thinus Marais – Medical Head: Influenza & COVID, Vaccines North America
Presenter’s disclosures
Pedro Folegatti , MD DTM&H MSc Dphil
is a full -time employee of Sanofi and may hold shares
in the company
MAT-US-2504669 P v3.0 EXP 28 APR 2026
Recombinant technology ensures sequence integrity of
antigens consistent with WHO -identified strains for
seasonal vaccine formulation
BEVS, baculovirus expression vector system; CBER, Center  for Biologics Evaluation and Research;  HA, hemagglutinin; MDCK, Madin -Darby Canine Kidney; NIBSC,  National Institute for Biological Standards and
Control;  rHA, recombinant haemagglutinin; rHA0, recombinant influenza virus hemagglutinins; SF+, spodoptera  frugiperda  (fall armyworm) -positive ; TGA, Therapeutic Goods Administration ; VRBPAC, Vaccines and
Related Biological Products Advisory Committee;  WHO, World Health Organization.
Reference : Arunachalam AB, et al. NPJ Vaccines .2021;6:144. Selection of virus strains
for vaccine composition
(WHO, VRBPAC)
Virus genomeHA proteinWild-type virus
RIV is produced using the exact genetic
sequence of the HA protein derived from the WHO
selected influenza strains; no live virus is used in
the manufacturing processIn this novel production platform,
rHA is expressed in insect cells
using BEVSrHA molecules are subsequently extracted  from
the infected insect cells and purified  from the
clarified cell extract before formulationInactive
virus
Virus
componentsPurify and
formulate
Formulated
vaccineDevelop seed virus
(CBER, NIBSC, TGA)
Egg-adapted
seed virus
Cell-adapted
seed virus Infect egg/cells
with flu virusGrow and
harvest virus
Embryonated
chicken egg
Replicated
virusMDCK cells
(dog kidney)EGG CELL
Produce, harvest
HA proteinPurify and
formulate
Formulated
vaccineHA protein
(rHA0)HA protein sequenceAdd HA gene to
BaculovirusInfect SF+cells
with Baculovirus
SF+cells
(caterpillar)Baculovirus
with HA geneRECOMBINANT
MAT-US-2504669 P v3.0 EXP 28 APR 2026
Safety and efficacy of RIV in clinical studies and
real-world data
GMT, geometric mean titers; IIV4, quadrivalent inactivated influenza vaccine; RIV3, trivalent recombinant influenza vaccine; RIV4, quadrivalent recombi nant influenza vaccine; SC, seroconversion; US, United States
References: 1. Dunkle  LM, et al. N Engl J Med . 2017;376(25):2427 -36. 2. Dunkle  LM, et al. J Infect Dis. 2017;216(10):1219 -26. 3. Prevention and Control of Influenza with Vaccines: Interim Recommendations of the
Advisory Committee on Immunization Practices (ACIP), 2013 . Accessed August 2024. 4. Flublok ® Influenza Vaccine. Product Insert.Clinical data (RIV4)
•2 Phase III studies
–Adults 50 years of age and older1 during a season with predominantly antigenically drifted H3N2 strains
•RIV4 provided  30% (95% CI, 10 to 47)  to 43% (95% CI, 21 to 59) enhanced protection against influenza
disease vs IIV4
–Adults 18 to 49 years of age2
•Non-inferior to the same IIV4 comparator vaccine for 3 of 4 influenza (SC rates and GMTs)
First license and recommendation
•RIV3 was first licensed in the US in 2013, followed by approval of RIV4 in 2016 for adults ≥18 years of age
•ACIP recommends use of recombinant influenza vaccination from 20133
Real -world safety data:
•~38 million doses of RIV3 and RIV4 distributed cumulatively (Sanofi internal data as of 31 Jan 2024)
•Established clinical safety profile, well tolerated with no safety concerns4
MAT-US-2504669 P v3.0 EXP 28 APR 2026
Study design
•Phase III parallel, multi -center , open -label, non -randomized
•Immuno -bridging study
•36 centers in Europe (Spain, Poland, Czech Republic) and
the United States
•2022/2023  northern hemisphere influenza
Study population:
•Healthy children & adults; n=1334
•Aged 9 -49 years
Intervention:
•To receive a single dose of:
RIV4 (9 to 17y)
n = 667RIV4 (18 to 49y)
n = 667
Objectives & endpoints
Primary:
•To demonstrate the non -inferior HAI immune response of RIV4 for 4
strains in participants aged 9 to 17 years vs participants aged 18 to
49 years
–HAI titers at D29
–Seroconversion rates
Secondary:
•To describe the safety profile of RIV4 vaccine in all participants and
by age group
–Solicited & Unsolicited AEs
–MAAEs
–SAEs and AESIs
•To describe HAI immune responses induced by RIV4
Trial design (1/2)
Ab, antibody; AE, adverse event; AESI, adverse events of special interest; HAI, hemagglutination inhibiting antibody; MAAEs, medically attended adverse events; NAb, neutralizing antibody; RIV4, recombinant influenza
vaccine quadrivalent; SAEs, serious adverse events; US, United States.
MAT-US-2504669 P v3.0 EXP 28 APR 2026
Trial design (2/2)
AEs, adverse events; AESIs, adverse events of special interest; CI, confidence interval; D, Day; PC, Phone Call; GMTs, geomet ric mean titers; MAAEs, medically attended adverse event; NI, non -inferiority; RIV4,
quadrivalent recombinant influenza vaccine; SAEs, serious adverse events; VAC, vaccinationKey exclusion criteria
•Receipt of any vaccine in the 4 weeks before or after
enrolment
–COVID -19 vaccines were allowed within 2 weeks
(before or after enrolment)
•Influenza vaccine receipt in the 6 months preceding
enrolment
Statistical considerations
•Overall study power of 80%
–type II error <20% for the 8 NI tests (GMTs and
SC on 4 strains)
•Non-Inferiority Margin
–Lower bound of the two -sided 95% CI of the ratio
of GMTs between groups >0.667 for each strain
–Lower bound of the two -sided 95% CI of
seroconversion rates ≥ -10% for the 4 strains
VAC 1 6-months follow -up
Visit/Contact V01 PC1 V02 PC2
Time (Day) D01 D09 D29 D181
Unsolicited
Systemic
 AEsImmunogenicity
Safety Solicited
 AEsUnsolicited
AEs, MAAEsSAEs, AESIs
RIV4
Blood samplingGraphical Study design
MAT-US-2504669 P v3.0 EXP 28 APR 2026
7 OPTIONS XII Congress, Brisbane, Australia; 29 September – 2 October 2024  Participant disposition
Enrolment period
27 October 2022 – 01 May 2023
N, number of participants; V, visitN planned = 1334
N enrolled = 1308
9 to 17 years old
N planned = 66718 to 49 years old
N planned = 667
N at V01 = 648
N blood sample = 641
N vaccinated = 641N at V01 = 660
N blood sample = 658
N vaccinated = 658
Discontinued N = 19
•Protocol deviation = 6
•Withdrawal by subject = 2
•Withdrawal by parent/guardian = 2
•Lost to follow up = 9Discontinued N = 22
•Adverse event = 1
•Protocol deviation = 3
•Withdrawal by subject = 8
•Lost to follow up = 10*
N at V02 = 629
N blood sample = 626N at V02 = 638
N blood sample = 634
N completed the active phase = 629 N completed the active phase = 636*
Total completed active phase = 1265
N at 6 -month
follow up = 611N at 6 -month
follow up = 613Discontinued N = 2
•Adverse event = 1
•Withdrawal by subject = 1
MAT-US-2504669 P v3.0 EXP 28 APR 2026
8 OPTIONS XII Congress, Brisbane, Australia; 29 September – 2 October 2024  Baseline Characteristics
Overall, there were more females  than males (653 females [53.7%] and 562 males [46.3%])
and the male/female ratio was 0.86
The overall mean age of participants was 23.5 years ( ± 12.5)
•13 years ( ±2.48) in the 9 -17s and 34 years in the 18 -49s ( ±9.20)
Most participants (87.0%) were of “Not Hispanic or Latino” ethnicity
Most participants were White  (77.4%), followed by Black or African American
participants (18.9%)
MAT-US-2504669 P v3.0 EXP 28 APR 2026
Primary objective met
Non-inferiority of immune response: GMTs at Day 29
•Non-inferiority of RIV4 in participants 9 to 17 years of age versus participants 18 to 49 years of age was demonstrated for
GMT ratios of all 4 strains
GMTs at D29 after vaccination of 9 to 17 years vs 18 to 49 years
CI, confidence interval; GMT, geometric mean titers; HAI, hemagglutination inhibition;  RIV4, quadrivalent recombinant influenza vaccine1946
(1795; 2109)1975
(1771; 2202)
405
(362; 452)1941
(1779; 2118)982
(881; 1094) 604
(531; 687)258
(233; 285)1593
(1477; 1717)
110100100010000
A/H1N1 A/H3N2 B/Victoria B/YamagataGeometric mean of HAI antibody
titer (95% CI)
Influenza strain
9–17 years (D29) 18–49 years (D29)D29 GMT Ratios (95% CI): 9 to 17 years vs 18 to 49 years
1.98 ( 1.73; 2.27) 3.27 ( 2.76; 3.87) 1.57 ( 1.35; 1.82) 1.22 ( 1.09; 1.37)
MAT-US-2504669 P v3.0 EXP 28 APR 2026
•Non-inferiority of RIV4 in participants 9 to 17 years of age versus participants 18 to 49 years of age was demonstrated for
seroconversion of all 4 strains of influenza
9 to 17 years minus 18 to 49 years
Antigen/
strainDifference (%) (95% CI) Non-inferiority§
A/H1N1 1.92 (-2.78; 6.62) Y
A/H3N2 -0.59 (-4.41; 3.23) Y
B/Victoria 3.29 (-1.57; 8.14) Y
B/Yamagata 14.3 (9.17; 19.3) Y
M, number of participants with available data for the considered endpoint; N, total number of participants included in the st udy; §Non-inferiority for SC rates is demonstrated if the lower limit of
the 2-sided 95% CI is ≥ -10% for the 4 strainsImmunogenicity primary objective: Non -inferiority of immune response in terms of seroconversion rates after
vaccination of 9 to 17 years vs 18 to 49 years
CI, confidence interval; RIV4, quadrivalent recombinant influenza vaccine; SC, seroconversionPrimary objective met
Non-inferiority of immune response: Seroconversion
MAT-US-2504669 P v3.0 EXP 28 APR 2026
Safety overview
AR, adverse reactions ; AESI, adverse event of special interest; CI, confidence interval; MAAE, medically attended adverse event; SAE, serious adverse eventDuring the study, 10 participants (0.8%) reported at least 1 SAE and 66 participants (5.1%)
reported at least 1 MAAE. None of the SAEs and MAAEs were considered as related to the
vaccine
No deaths and no AESIs were reported during the study
No substantial differences in safety profile was observed between groups
MAT-US-2504669 P v3.0 EXP 28 APR 2026
Solicited reactions within 7 days of vaccinations
•Most solicited reactions were of Grade 1 or Grade 2 intensity, started within D1 -D4, and resolved (spontaneously) after 1 -3
days
•Within 28 days of vaccination, 0.9% of participants  in both age groups experienced at least 1 unsolicited injection site AR
rated as Grade 3
•Grade 3 solicited injection site reactions consisted predominantly of swelling  in 9 participants of 9 to 17 years group
(1.5%) and induration  in 5 participants of 18 to 49 years (0.8%)
•Grade 3 solicited systemic reactions consisted predominantly of headache  and malaise  reported by 16 participants (2.6%,
each) in 9 to 17 years group. Grade 3 malaise  was reported by 10 participants (1.6%) in 18 to 49 years groups
AR, adverse reaction; D, day44.3
6.535.6
3.129.6
4.652.9
4.640.8
1.436.2
3.1
0102030405060
Solicited reaction Grade 3 solicited reaction Solicited injection site
reactionGrade 3 injection site
reactionSolicited systemic reaction Grade 3 systemic reactionParticipants experiencing at
least one (%)
9 to 17 years 18 to 49 yearsSummary of solicited reactions within 7 days after vaccine injection
MAT-US-2504669 P v3.0 EXP 28 APR 2026
Solicited injection site reactions after vaccine injection
AR, adverse reaction
Summary of solicited injection site reactions after vaccination
22.22.81.31.81.5
11.30.61.00.50.5
0.81.11.50.80.5
0 5 10 15 20 25Injection site painInjection site erythemaInjection site swellingInjection site indurationInjection site bruising
Percentage of participants experiencing at least one AR (%)
Grade 3 Grade 2 Grade 131.21.30.81.90.5
8.70.91.40.60.2
0.30.50.50.80.5
0 5 10 15 20 25 30 35Injection site painInjection site erythemaInjection site swellingInjection site indurationInjection site bruising
Percentage of participants experiencing at least one AR (%)
Grade 3 Grade 2 Grade 12.5
3.1
3.8
4.5
34.31.2
3.3
2.7
2.7
40.29 to 17 years
 18 to 49 years
MAT-US-2504669 P v3.0 EXP 28 APR 2026
Solicited systemic reactions after vaccine injection
AR, adverse reaction
1.00.7
16.1
2.88.55.79.13.3
7.57.88.83.4
1.02.62.61.50.7
0 2 4 6 8 10FeverHeadacheMalaiseMyalgiaChills
Percentage of participants experiencing at least one AR (%)
Grade 3 Grade 2 Grade 11.19.45.29.43.1
0.212.19.89.92.5
0.51.31.60.90.6
0 2 4 6 8 10 12 14FeverHeadacheMalaiseMyalgiaChills
Percentage of participants experiencing at least one AR (%)
Grade 3 Grade 2 Grade 16.2
20.2
16.6
22.8
1.89 to 17 years
 18 to 49 years
1.0
0.87.4
19.4
18.6
MAT-US-2504669 P v3.0 EXP 28 APR 2026
13 SAEs reported in the study:
All events classified as unrelated by Sponsor and
Investigator
*All participants reporting Psychiatric Disorders SAEs had past medical history of
mental health disorders prior to enrollment
^Neurology review attributed event to amphetamine use, sleep deprivation and
metabolic disorder
MAT-US-2504669 P v3.0 EXP 28 APR 2026•7 participants reported  9 SAEs
•Within 28 days
•Major Depression  and Intentional
Overdose*
•Gastric Cancer Recurrent
•Suicidal Ideation*
•Seizure^
•Acute Respiratory Failure and
Overdose
•During Follow -up
•Kidney Infection
•Obstructive Pancreatitis•3 participants reported 4 SAEs
•Within 28 days
•Suicidal Ideation and worsening of
Suicidal Ideation*
•During Follow -up
•Suicidal Ideation*
•Spinal Fracture (post trauma)
 18-49 years of age 9-17 years of age
Conclusion
•RIV induced a robust immune response in participants 9 to 17 years and 18 to 49 years
•These findings are consistent with previous research1-5
•Non-Inferiority  of HAI immune response induced in those 9 to 17 years of age versus those 18 to 49 years
of age as assessed by GMTs and SC rates at D29 was met for all 4 influenza strains
•The safety profile of the RIV4 vaccine was comparable in both age groups
D, Day; GMT, geometric mean titer; HAI, hemagglutination inhibition; NI, non -inferiority; RIV, recombinant influenza vaccine; SC, seroconversion
References: 1. Hasio  A, et al. N Engl J Med. 2023;389:2245 -2255. 2. Zimmerman RK, et al. Vaccine . 2023;41(35):5134 -5140. 3. Dunkle LM et al. N Engl J Med. 2017;376:2427 -2436.  4. Dunkle  et al.
Pediatrics .2018;141(5):3021. 5. James C King et al. Vaccine . 2009 Nov 5;27(47):6589 -94.
MAT-US-2504669 P v3.0 EXP 28 APR 2026
Funding
Funding
This study was funded and
sponsored by Sanofi
MAT-US-2504669 P v3.0 EXP 28 APR 2026
Thank you
©Sanofi 2025. All Rights Reserved.          MAT-US-2504669 P v2.0 EXP 28 APR 2026
Baseline demographics by age group
9 to 17 years
(N=609)18 to 49 years
(N=606)All
(N=1215)
Sex, n (%)
Male 316 (51.9) 246 (40.6) 562 (46.3)
Female 293 (48.1) 360 (59.4) 653 (53.7)
Age, mean (SD), Year 13.0 (2.48) 34.1 (9.20) 23.5 (12.5)
Racial origin , n (%)
American Indian or Alaska Native 4 (0.7) 0 4 (0 .3)
Asian 1 (0.2) 6 (1.0) 7 (0 .6)
Black or African American 140 (23.0) 90 (14.9) 230 (18.9)
Native Hawaiian or Other Pacific Islander 1 (0.2) 2 (0.3) 3 (0.2)
White 447 (73.4) 493 (81.4) 940 (77.4)
Not Reported 0 2 (0.3) 2 (0.2)
Unknown 1 (0.2) 1 (0.2) 2 (0.2)
Multiple 15 (2.5) 12 (2.0) 27 (2.2)
Ethnicity, n (%)
Hispanic or Latino 107 (17.6) 35 (5.8) 142 (11.7)
Not Hispanic or Latino 494 (81.1) 563 (92.9) 1057 (87.0)
Not reported 7 (1.1) 8 (1.3) 15 (1.2)
Unknown 1 (0.2) 0 1 (<0.1)
n, number of study participants fulfilling the item listed; N, total number of participants included in the study; SD, standa rd deviation
MAT-US-2504669 P v3.0 EXP 28 APR 2026
HAI antibody titers
Ab, antibody; CI, confidence interval; D, day; GMT, geometric mean titer; GMTRs, HAI Ab GMT ratios;  HAI, hemagglutination inhibition
•At baseline, the HAI Ab GMTs were higher in participants 9 to 17 years of age than in participants 18 to 49 years of
age for the A/H1N1, A/H3N2, B/Victoria lineage, and were similar in both age groups for B/Yamagata lineage strain
•At D29, the HAI Ab GMTs increased in both age groups and were higher in participants 9 to 17 years of age than in
participants 18 to 49 years of age for all virus strains
HAI Ab GMTs ( 95% CI ) at baseline HAI Ab GMTs ( 95% CI ) at D29
Antigen/ strain 9 to 17 years 18 to 49 years 9 to 17 years 18 to 49 years
A/H1N1 154 (137; 173) 74.9 (65.8; 85.1) 1946 (1795; 2109) 982 (881; 1094)
A/H3N2 111 (95.4; 128) 29.0 (25.7; 32.8) 1975 (1771; 2202) 604 (531; 687)
B/Victoria 48.1 (43.0; 53.8) 37.3 (34.0; 40.9) 405 (362; 452) 258 (233; 285)
B/Yamagata 272 (243; 305) 300 (269; 335) 1941 (1779; 2118) 1593 (1477; 1717)GMTs at baseline and D29 after vaccination of 9 to 17 years vs 18 to 49 years
MAT-US-2504669 P v3.0 EXP 28 APR 2026
Geometric mean of HAI antibody titer
154
111
48.127219461975
4051941
74.9
2937.3300982
604
2581593
110100100010000
A/H1N1 A/H3N2 B/Victoria B/YamagataGeometric mean of HAI antibody titer (95% CI)
Influenza strain
D01 (9 to 17 years) D29 (9 to 17 years) D01 (18 to 49 years) D29 (18 to 49 years)
CI, confidence interval; D, day; HAI, hemagglutination inhibition
MAT-US-2504669 P v3.0 EXP 28 APR 2026
Non-inferiority of immune response: GMTs at Day 29
•Non-inferiority of RIV4 in participants 9 to 17 years of age versus participants 18 to 49 years of age was demonstrated for
all 4 ratios of GMTs
9 to 17 years
(N=609)18 to 49 years
(N=606)9 to 17 years / 18 to 49 years
Antigen/
strainM GMT (95% Cl) M GMT (95% Cl) GMT Ratio (95% CI)Non-
inferiority§
A/H1N1 609 1946 (1795; 2109) 606 982 (881; 1094) l.98(1.73;
2.27)Y
A/H3N2 609 1975 (1771; 2202) 606 604 (531; 687) 3.27(2.76;
3.87)Y
B/Victoria 609 405 (362; 452) 606 258 (233; 285) 1.57(1.35;
1.82)Y
B/Yamagata 609 1941 (1779; 2118) 606 1593 (1477; 1717) 1.22(1.09;
1.37)YGMTs at D29 after vaccination of 9 to 17 years vs 18 to 49 years
; §Non-inferiority is concluded if the lower limit of the two -sided 95% CI of the ratio of GMTs between groups (9 to 17 years/18 to  49 years) is > 0.667 for each strain
CI, confidence interval; D, day; GMT, geometric mean titers; M, number of participants with available data for the considered endpoint; N, total number of participants; RIV4, quadrivalent recombinant influenza vaccine
MAT-US-2504669 P v3.0 EXP 28 APR 2026
Individual HAI antibody titer ratios
CI, confidence interval; D, day; GMT, geometric mean titer; GMTRs, HAI Ab GMT ratios;  HAI, hemagglutination inhibition •The post -vaccination GMTRs (D29/D01) were similar in both age groups for A/H1N1, A/H3N2, and B/Victoria lineage
strains and were higher in participants 9 to 17 years of age than in participants 18 to 49 years of age for B/Yamagata
lineage strain
GMTRs (95% CI)
Antigen/ strain 9 to 17 years 18 to 49 years
A/H1N1 12.7 (11.1; 14.5) 13.1 (11.4; 15.0)
A/H3N2 17.9 (15.7; 20.3) 20.8 (18.4; 23.6)
B/Victoria 8.41 (7.55; 9.37) 6.91 (6.25; 7.64)
B/Yamagata 7.13 (6.46; 7.87) 5.31 (4.79; 5.88)
MAT-US-2504669 P v3.0 EXP 28 APR 2026
HAI antibody titer ≥40 (1/ dil) and HAI antibody titer ≥10
(1/dil)
CI, confidence interval; D, day; HAI, hemagglutination inhibition•At baseline, the percentages of participants with HAI Ab titer ≥40 (1/ dil) and HAI antibody titer ≥10 (1/ dil) were higher in participants 9 to
17 years of age than in participants 18 to 49 years of age for the A/H1N1 and A/H3N2, and were similar in both age groups for  B/Victoria
and B/Yamagata lineage strains
•At D29, the percentages of participants with HAI Ab titer ≥40 (1/ dil) and HAI antibody titer ≥10 (1/ dil) increased for all 4 virus strains and
were high in both age groups
D01 D29
Percentage of
participants with
HAI antibody
titer ≥ 40 (95%
CI)Antigen/
strain9 to 17 years 18 to 49 years 9 to 17 years 18 to 49 years
A/H1N1 87.2 (84.3; 89.7) 71.8 (68.0; 75.3) 99.7 (98.8; 100) 97.5 (96.0; 98.6)
A/H3N2 74.7 (71.1; 78.1) 45.0 (41.0; 49.1) 99.0 (97.9; 99.6) 95.0 (93.0; 96.6)
B/Victoria 61.4 (57.4; 65.3) 59.8 (55.8; 63.8) 95.6 (93.6; 97.1) 97.0 (95.3;98.2)
B/Yamagata 93.1 (90.8; 95.0) 95.2 (93.2; 96.8) 99.5 (98.6; 99.9) 100 (99.4; 100)
Percentage of
participants with
HAI antibody
titer ≥ 10 (95%
CI)A/H1N1 97.0 (95.4; 98.2) 89.8 (87.1; 92.1) 100 (99.4;100) 99.3 (98.3; 99.8)
A/H3N2 89.2 (86.4; 91.5) 77.7 (74.2; 81.0) 100 (99.4; 100) 99.7 (98.8; 100)
B/Victoria 92.1 (89.7; 94.1) 91.7 (89.2; 93.8) 99.5 (98.6; 99.9) 99.8 (99.1; 100)
B/Yamagata 97.9 (96.4; 98.9) 99.5 (98.6;99.9) 100 (99.4; 100) 100 (99.4; 100)
MAT-US-2504669 P v3.0 EXP 28 APR 2026
Seroconversion
SC, seroconversion •The SC rates were similar in both age groups for A/H1N1, A/H3N2, B/Victoria lineage strains and higher in
participants 9 to 17 years of age than in participants 18 to 49 years of age for B/Yamagata lineage strain
SC (% [95% CI])
Antigen/ strain 9 to 17 years 18 to 49 years
A/H1N1 78.3 (74.8; 81.5) 76.4 (72.8; 79.7)
A/H3N2 86.5 (83.6; 89.1) 87.1 (84.2; 89.7)
B/Victoria 76.8 (73.3; 80.1) 73.6 (69.8; 77.0)
B/Yamagata 77.2 (73.6; 80.5) 62.9 (58.9; 66.7)
MAT-US-2504669 P v3.0 EXP 28 APR 2026
Neutralizing Ab titers  (SN assay) at D01 and D29 after
vaccination
Ab, antibody; D, day; GMTR, geometric mean titer ratio; HAI, hemagglutination inhibition; SN, seroneutralization •The post -vaccination SN Ab GMTRs were similar in both age groups for A/H1N1, B/Victoria lineage, and B/Yamagata lineage
strains
•It was higher  in participants 9 to 17 years of age than in participants 18 to 49 years of age for A/H3N2 strain
614
200
65.84667529
1406
5453733
258
117
34.23204048
564
2402212
1101001000
A/H1N1 A/H3N2 B/Victoria B/YamagataGeometric mean
Influenza strain
Pre-dose D01 (9 to 17 years) Post-dose D29 (9 to 17 years) Pre-dose D01 (18 to 49 years) Post-dose D29 (18 to 49 years)
GMTRs (D29/D01) per strain and age group
12.2
(9.4; 15.8)15.5
(11.8; 20.3)7.0
(5.9; 8.3)4.8
(4.1; 5.6)8.3
(6.7; 10.3)7.1
(5.8; 8.6)8.0
(6.5; 9.8)6.8
(5.5; 8.5)
MAT-US-2504669 P v3.0 EXP 28 APR 2026
Summary of geometric mean of HAI antibody titer at
baseline (D01) and D29 by age subgroup
Ab, antibody; CI, confidence interval; D, day; GM, geometric mean; HAI, hemagglutination inhibition; M, number of participants with available data for the considered endpoi nt; V, visit 9 to 11 years
(N=186)12 to 17 years
(N=423)18 to 34 years
(N=303)35 to 49 years
(N-303)
Strain Time Point M GM (95% CI) M GM (95% CI) M GM (95% CI) M GM (95% CI)
A/H1N1 V01 (D01) 186 139 (112; 173) 423 160 (139; 184) 303 102 (85.2; 122) 303 55.0 (46.0; 65.7)
V02 (D29) 186 2101 (1786; 2472) 423 1881 (1717; 2062) 303 1499 (1313; 1711) 303 643 (549; 753)
A/H3N2 V01 (D01) 186 152 (117; 198) 423 96.1 (80.6; 115) 303 27.7 (23.2; 33.0) 303 30.4 (25.6; 36.0)
V02 (D29) 186 2550 (2129; 3055) 423 1765 (1543; 2019) 303 644 (536; 775) 303 567 (473; 679)
B/Victoria V01 (D01) 186 36.3 (30.4; 43.4) 423 54.4 (47.4; 62.6) 303 36.5 (32.0; 41.7) 303 38.1 (33.6; 43.3)
V02 (D29) 186 308 (248; 383) 423 456 (402; 517) 303 270 (232; 315) 303 247 (216; 281)
B/Yamagata V01 (D01) 186 169 (136; 210) 423 336 (296; 381) 303 435 (377; 501) 303 207 (178; 242)
V02 (D29) 186 1339 (1101; 1627) 423 2286 (2094; 2496) 303 2211 (2026; 2414) 303 1147 (1026; 1282)Table 5: Summary of geometric mean of HAI antibody titer at baseline (D01) and D29 by age subgroup
MAT-US-2504669 P v3.0 EXP 28 APR 2026
Summary of geometric mean of HAI antibody titer at
baseline (D01) and D29 by priming status
CI, confidence interval; D, day; GM, geometric mean; HAI, hemagglutination inhibition; M, number of participants with available data for the considered endpoi nt; V, visit 9 to 17 years 18 to 49 years
Previously unvaccinated*
(N-425)Previously vaccinated†
(N=180)Previously unvaccinated*
(N=409)Previously vaccinated†
(N=193)
Strain Time Point M GM (95% CI) M GM (95% CI) M GM (95% CI) M GM (95% CI)
A/H1N1 V01 (D01) 425 123 (107; 142) 180 255 (208; 313) 409 50.1 (43.2; 58.1) 193 168 (137; 207)
V02 (D29) 425 2276 (2072; 2501) 180 1351 (1169; 1561) 409 1152 (1004; 1322) 193 698 (591; 824)
A/H3N2 V01 (D01) 425 103 (85.5; 123) 180 135 (105; 173) 409 24.7 (21.3; 28.5) 193 39.9 (31.9; 49.7)
V02 (D29) 425 2054 (1804; 2339) 180 1838 (1502; 2250) 409 648 (553; 759) 193 518 (414; 647)
B/Victoria V01 (D01) 425 37.7 (32.9; 43.1) 180 86.7 (72.8; 103) 409 29.8 (26.7; 33.1) 193 59.0 (50.6; 68.7)
V02 (D29) 425 399 (348; 457) 180 422 (348; 512) 409 270 (238; 306) 193 236 (199; 280)
B/Yamagata V01 (D01) 425 215 (187; 247) 180 474 (401; 560) 409 240 (210; 275) 193 478 (406; 564)
V02 (D29) 425 1995 (1785; 2229) 180 1803 (1575; 2064) 409 1784 (1629; 1955) 193 1266 (1113; 1441)Table 17: Summary of geometric mean of HAI antibody titer at baseline (D01) and D29 by priming status
MAT-US-2504669 P v3.0 EXP 28 APR 2026
Summary of geometric mean of HAI antibody titer at
baseline (D01) and D29 by baseline seropositivity
Ci, confidence interval; D, day; GM, geometric mean; HAI, hemagglutination inhibition; M, number of participants with available data for the considered endpoi nt; V, visit 9 to 17 years 18 to 49 years
Baseline seropositive for Baseline seronegative for Baseline seropositive for Baseline seronegative for
Strain Time Point M GM (95% CI) M GM (95% CI) M GM (95% CI) M GM (95% CI)
A/H1N1 V01 (D01) 591 170 (153; 190) 18 5.00 (NC; NC) 544 102 (90.6; 115) 62 5.00 (NC; NC)
V02 (D29) 591 1989 (1839; 2152) 18 941 (391; 2265) 544 1181 (1071; 1303) 62 193 (123; 305)
A/H3N2 V01 (D01) 543 161 (141; 184) 66 5.00 (NC; NC) 471 48.0 (42.4; 54.4) 135 5.00 (NC; NC)
V02 (D29) 543 2518 (2289; 2770) 66 268 (184; 390) 471 915 (809; 1036) 135 142 (109; 186)
B/Victoria V01 (D01) 561 58.4 (52.5; 65.0) 48 5.00 (NC; NC) 555 44.7 (41.1; 48.6) 50 5.00 (NC; NC)
V02 (D29) 561 471 (424; 524) 48 68.3 (45.1; 103) 555 280 (253; 310) 50 101 (69.0; 149)
B/Yamagata V01 (D01) 596 297 (268; 330) 13 5.00 (NC; NC) 603 306 (275; 341) 3 5.00 (NC; NC)
V02 (D29) 596 2076 (1918; 2248) 13 89.0 (37.3; 212) 603 1596 (1480; 1722) 3 1016 (NC; NC)Table 21: Summary of geometric mean of HAI antibody titer at baseline (D01) and D29 by baseline seropositivity
MAT-US-2504669 P v3.0 EXP 28 APR 2026
Safety overview
•During the study, 10 participants (0.8%) reported at least 1 SAE and 66 participants (5.1%) reported at least 1 MAAE.
None of the SAEs and MAAEs were considered as related to the vaccine
•No deaths and no AESIs were reported during the study
Safety overview after vaccine injection
9 to 17 years
(N=641)18 to 49 years
(N=658)All
(N=1299)
Period/Participants experiencing
at least one:n/M % (95% Cl) n/M % (95% Cl) n/M % (95% Cl)
Within 28 days after vaccine injection
Unsolicited AR 30/641 4.7 (3.2; 6.6) 26/658 4.0 (2.6; 5.7) 56/1299 4.3 (3.3; 5.6)
AE leading to discontinuation 0/641 0 (0; 0.6) 2/658 0.3 (0; 1.1) 2/1299 0.2 (0; 0.6)
During the study
SAE 3/641 0.5 (0.1; 1.4) 7/658 1.1 (0.4; 2.2) 10/1299 0.8 (0.4; 1.4)
Death 0/641 0 (0; 0.6) 0/658 0 (0; 0.6) 0/1299 0 (0; 0.3)
AESI 0/641 0 (0; 0.6) 0/658 0 (0; 0.6) 0/1299 0 (0; 0.3)
MAAE 29/641 4.5 (3.1; 6.4) 37/658 5.6 (4.0; 7.7) 66/1299 5.1 (4.0; 6.4)
M, number of participants with available data for the relevant endpoint; n, number of participants experiencing the endpoint listed in the first column; N, total number of participants included in
the study
AR, adverse reactions ; AESI, adverse event of special interest; CI, confidence interval; MAAE, medically attended adverse event; SAE, serious adverse event
MAT-US-2504669 P v3.0 EXP 28 APR 2026

Summary: VAP00027 Immunogenicity and Safety of Quadrivalent Recombinant  Influenza Vaccine (RIV4) in Children and Adolescents  Aged 9 to 17 Years and Adults Aged 18 to 49 Years For the Advisory Committee of Immunization Practices (ACIP) Influenza Working Group MAT-US-2504669 P v3.0 EXP 28 APR 2026Pedro Folegatti   – Global Clinical Development Director (Presenter) Thinus Marais – Medical Head: Influenza & COVID, Vaccines North America Presenter’s disclosures Pedro Folegatti , MD DTM&H MSc Dphil  is a…


03 dugan influenza 508

Severity, Disease Burden, and Prevented Burden for
the 2024 -2025 Influenza Season
Influenza Division, CDC

2024 -2025 Influenza Season News

Influenza Severity Assessment by Season and  by Age Group
Severity Classification by Age Group
Influenza Season* 0-17 years 18-64 years ≥65 years All Ages
2009- 2010 Very High Moderate Low Moderate
2010- 2011 Moderate Moderate Moderate Moderate
2011- 2012 Low Low Low Low
2012- 2013 Moderate Moderate High Moderate
2013- 2014 Moderate Moderate Moderate Moderate
2014-2015 Moderate Moderate High High
2015- 2016 Low Moderate Low Moderate
2016- 2017 Moderate Moderate Moderate Moderate
2017- 2018 High High High High
2018- 2019 Moderate Moderate Moderate Moderate
2019- 2020 High High Moderate Moderate
2021- 2022 Low Low Low Low
2022- 2023 High Moderate Moderate Moderate
2023- 2024 Moderate Moderate Moderate Moderate
2024-2025 High High High High
*Severity assessment was not completed for 2020 -2021 season because of minimal influenza activity
Influenza Disease Burden Estimation
•Influenza is not a notifiable , reportable disease in the U.S.
-Except for pediatric deaths
•Sentinel surveillance systems in healthcare settings cannot capture all
influenza virus infections
•Not everyone who is ill seeks medical care
•Not everyone who seek medical care will be tested for influenza
•Even if someone with influenza seeks care and is tested, depending on where
in the course of an illness and type of specimen collected, they may test negative
•Influenza symptoms are non -specific and individuals could be misdiagnosed
with having a different respiratory illness especially when not testedWhy it is necessary to estimate influenza disease burden
https://www.cdc.gov/flu -burden/php/about/why -cdc-estimates.html
•Disease burden is estimated by
clinical disease severity
•Calculated using five age groups:
-0-4 years
-5-17 years
-18-49 years
-50-64 years
-65+ yearsU.S. Annual Influenza Burden Estimates
Deaths
Hospitalizations
Medically attended
illnesses
Community symptomatic
illnesses
Hospitalizations
(Crude hospitalization rate) x (adjustment for
testing practices) x population1
Symptomatic community illness
(Hospitalizations) x ( case:hospitalization  ratio)3Outpatient medical visits:
(Symptomatic community illness) x
(probability of seeking medical care when ill)4Deaths
(Hospitalizations) x
(death:hospitalization  ratio)2Data Source
Cause of death from death
certificate, risk of death when hospitalized, and location of death (in vs. out of hospital (ref 1)
Routine sentinel surveillance for patients hospitalized with
laboratory -confirmed
influenza and data from a
survey of influenza testing
practices at sentinel hospitals
(ref 1)
Telephone survey of healthcare -seeking behavior
during influenza -like illness
(ref 3)
Field investigations of influenza (ref 2)Burden level
MethodologyStep
#Legend
1: R eed, et al., PLoS One. 2015
2: R eed , et al., EID. 2009
3: Biggerstaff, et al., AJPH . 2012
Preliminary Influenza Disease Burden, 2024- 2025 by Age Group
Age GroupSymptomatic Illnesses
(95% Uncertainty
Interval)Medically Attended Illnesses
(95% Uncertainty Interval)Hospitalizations
(95% Uncertainty
Interval)
0-4 years3,600,000
(2,900,000, 5,800,000)2,400,000
(1,800,000, 4,000,000)25,000
(20,000, 40,000)
5-17 years11,000,000
(8,600,000, 24,000,000)5,800,000
(4,100,000, 12,000,000)31,000
(24,000, 65,000)
18-49 years22,000,000
(16,000,000, 38,000,000)8,100,000
(5,300,000, 14,000,000)120,000
(91,000, 210,000)
50-64 years14,000,000
(10,000,000, 31,000,000)6,000,000
(3,700,000, 13,000,000)150,000
(110,000, 320,000)
≥65 years4,900,000
(3,400,000, 11,000,000)2,700,000
(1,700,000, 6,200,000)440,000
(310,000, 990,000)
Total56,000,000
(47,000,000, 83,000,000)25,000,000
(20,000,000, 38,000,000)770,000
(620,000, 1,400,000)
Influenza Disease Burden Varied by Season
23,000,000
9,400,00034,000,00030,000,000 30,000,000
24,000,00029,000,00041,000,000
29,000,00034,000,000
11,000,00031,000,00040,000,00056,000,000 11,000,000
4,400,00016,000,000
13,000,000 14,000,000
11,000,00014,000,00019,000,000
14,000,00015,000,000
5,100,00014,000,00018,000,00025,000,000
2010-11 2011-12 2012-13 2013-14 2014-15 2015-16 2016-17 2017-18 2018-19 2019-20 2021-22 2022-23 2023-24 2024-25Number of Symptomatic Illnesses, Medical Visits, and
Hospitalizations
SeasonSymptomatic Illnesses Medical Visits Hospitalizations
140,000580,000
350,000590,000
280,000500,000710,000
400,000380,000
120,000370,000470,000770,000
310,000
* * *
*Preliminary Estimates
Influenza Vaccine Prevented Influenza
Disease Burden Estimation
Influenza Vaccine Prevented Disease Burden Components
56 million
illnesses
770,000 hospitalizations25 million medical visits
35–71%
(Varies by age group)38–56%
(Varies by age
group
and flu type)Disease Burden Vaccine Coverage Vaccine Effectiveness
Outpatient
Inpatient
39–62%
(Varies by age
group
and flu type)
Data Sources: Vaccine Coverage: NIS-FLU, BRFSS ; Outpatient VE estimates: VE Network , NVSN , VISION Network ;
Inpatient VE estimates: NVSN, VISION Network, IVY
https://www.cdc.gov/flu -burden/php/about -burden- prevented/index.html
Influenza Prevented Disease Burden Model
Estimated
Medical VisitsEstimated
HospitalizationsEstimated
Deaths
Observed burden
outcomes with
vaccinationExpected burden
outcomes without
vaccinationBurden outcomes
prevented by
vaccination
Use vaccine coverage
(VC) and vaccine
effectiveness (VE)
estimate risk to
susceptible personsApply risk of burden
outcomes among
susceptible persons to
hypothetical susceptible
population without
vaccinationMonte Carlo
simulation
methodology to
estimate uncertaintyDisease
burden model
Prevented
disease burden
model
Calculated monthly
by age groupEstimated
InfectionsAdjusted
Hospitalization
Rates
∝
1-VE, 1 -VC
Preliminary Influenza Disease Burden Prevented by Vaccination, 2024-
2025 by Age Group
Age Group Symptomatic Illnesses Medically Attended Illnesses Hospitalizations
0-4 years1,200,000
(910,000, 2,000,000)810,000
(600,000, 1,300,000)9,700
(7,300, 16,000)
5-17 years2,200,000
(1,600,000, 4,800,000)1,200,000
(840,000, 2,500,000)7,700
(5,600, 17,000)
18-49 years3,800,000
(2,700,000, 6,400,000)1,400,000
(1,000,000, 3,000,000)18,000
(13,000, 31,000)
50-64 years3,300,000
(2,300,000, 7,300,000)1,400,000
(1,000,000, 3,000,000)32,000
(22,000, 63,000)
≥65 years1,600,000
(1,100,000, 3,500,000)900,000
(600,000, 2,000,000)170,000
(120,000, 380,000)
Total12,000,000
(10,000,000, 18,000,000)5,700,000
(4,800,000, 8,400,000)240,000
(180,000, 460,000)
Influenza Disease and Prevented Burden 2011 -2024†Number of Illnesses, Hospitalizations, and Deaths140,000580,000
350,000590,000
280,000500,000710,000
400,000 380,000
120,000370,000470,000770,000
45,000119,000
120,000112,000
73,00065,00083,000
36,000 98,000
26,00071,000120,000240,000Hospitalizations Prevented Hospitalizations
9,400,00034,000,00030,000,000 30,000,00024,000,00029,000,00041,000,000
29,000,00034,000,000
11,000,00031,000,00040,000,00056,000,000
2,300,0008,100,0008,000,0003,200,000
5,600,0004,900,0006,000,000
2,800,0006,700,000
1,900,0005,500,0009,800,00012,500,000
2011-12 2012-13 2013-14 2014-15 2015-16 2016-17 2017-18 2018-19 2019-20 2021-22 2022-23 2023-24 2024-25Symptomatic Illnesses Prevented Sympotmatic Illnesses11,000,000
4,400,00016,000,00013,000,000 14,000,00011,000,00014,000,00019,000,00014,000,000 15,000,000
5,100,00014,000,00018,000,00025,000,000 3,100,000
1,100,0004,000,000
3,700,000 1,700,0002,700,0002,500,0003,100,000
1,500,0003,300,000
990,0002,700,0004,800,0005,700,000Medical Visits Prevented Medical Visits
*
*Preliminary Estimates; †https://www.cdc.gov/flu -burden/php/data -vis-vac/past -burden -prevented -est.html
 * *
•Influenza causes significant impacts on healthcare settings and substantial
disease burden on the population
•2024- 2025 season was classified as high severity for all age ages and by age
group and is the first high severity season since 2017- 2018
•Estimated influenza disease burden was the highest the U.S. has seen in the
last decade
•Influenza vaccine prevented an estimated 240,000 hospitalizations, most in
adults aged 65 years and older, and likely prevented the season from being even more severeConclusions
For more information, contact CDC
1-800- CDC- INFO (232 -4636)
TTY:  1 -888- 232- 6348    cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the U.S. Centers for Disease Control and Prevention.

Summary: Severity, Disease Burden, and Prevented Burden for  the 2024 -2025 Influenza Season Influenza Division, CDC  2024 -2025 Influenza Season News  Influenza Severity Assessment by Season and  by Age Group Severity Classification by Age Group Influenza Season* 0-17 years 18-64 years ≥65 years All Ages 2009- 2010 Very High Moderate Low Moderate 2010- 2011 Moderate Moderate Moderate Moderate 2011- 2012 Low Low Low Low 2012- 2013 Moderate Moderate High Moderate 2013- 2014 Moderate Moderate Moderate…


04 dugan influenza 508

U.S. Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation
use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.
2024 -25 Influenza Season Update and Seasonal Influenza
Vaccine Recommendations for the 2025 -26 U.S. Influenza
Season
Dr. Vivien Dugan
Influenza Division, CDC/NCIRD
June 26, 2025
2024 -25 influenza season summary
Proposed updates to the seasonal influenza vaccine recommendations
for the 2025 -26 influenza season including the following recent FDA
approvals:
–Influenza vaccine composition for the 2025 -26 season
–FluMist (live attenuated influenza vaccine, trivalent) for self -or caregiver
administration
–Change in age indication for Flublok (recombinant influenza vaccine, trivalent)
from ≥18 years to ≥9 yearsOverview
2
2024 -25 Influenza Season
High severity season overall and for all age groups
–First high severity season since 2017 -2018
Highest cumulative influenza -associated hospitalization rate since
2010 -2011
–October 1, 2024 through April 30, 2025: 128.1 per 100,000
–Cumulative rate was 102.9 per 100,000 for the severe 2017 -18 season
As of June 7, 246 influenza -associated pediatric deaths have been
reported this season2024 -25 U.S. Influenza Season
4Weekly US Influenza Surveillance Report: Key Updates for Week 20, ending May 17, 2025 | FluView | CDC
Weekly US Influenza Surveillance Report: Key Updates for Week 23, ending June 7, 2025 | FluView | CDC
Influenza -Associated Hospitalizations, FluSurv -NET, 2024 -
2025 Season
Lab -confirmed influenza -associated hospitalizations in
select counties in 14 states
Approx. 9% of  U.S. population
As of May 17, cumulative rate of 128.1 per 100,00
–Was 102.9 for 2017 -18
Approx 16% of hospitalized patients required ICU
admission and 6% required invasive mechanical ventilation
Weekly US Influenza Surveillance Report: Key Updates for Week 20, ending May 17, 2025 | FluView | CDC5103.4
39.8 51.9149.7403.4
0100200300400500
0-4 5-17 18-49 50-64 ≥65Rate (per 100,000 population)
Age groupCumulative rate of laboratory -confirmed influenza
hospitalizations by age - FluSurv -NET, 2024 -25 season102.9
020406080100120140Rate per 100,000 population
Influenza SeasonCumulative rate of laboratory -confirmed influenza
hospitalizations by season –– FluSurv- NET,  2010- 11 –  2024 -25
seasons
128.1
Influenza- Associated Pediatric Mortality,
2024 -2025 Season*
Death in a person <18 yrs of age
–with clinically compatible illness
–and influenza positive laboratory test
–and no period of complete recovery
between illness and death
Nationally notifiable since 2004
246 deaths reported*
All age groups affected
•0-5 months:   7%
•6-23 months: 13%
•2-4 years: 18%
•5-11 years: 37%
•12-17 years: 26%
* Through June 7, 2025 https://gis.cdc.gov/GRASP/Fluview/PedFluDeath.html 6
Influenza- Associated Pediatric Mortality,
2024 -2025 Season*
Among 246 influenza -associated pediatric deaths reported thus far
for 2024-25*,
–42% had no known high risk underlying medical condition
–40% had a bacterial co -infection of a sterile site
–89% of those eligible for influenza vaccination were not fully vaccinated
•Compared with 82% for the 2023 -24 season
Highest number of pediatric deaths reported in any non -pandemic
influenza season since condition became reportable in 2004
* Through June 7, 2025 https://gis.cdc.gov/GRASP/Fluview/PedFluDeath.html 7
2025 -26 Seasonal Influenza Vaccine
Recommendations
8
Annual influenza vaccination remains recommended for those aged
≥6 months who do not have contraindications
As previously,
–No preferential recommendations are made with the exception that high- dose
inactivated, recombinant, and adjuvanted inactivated influenza vaccines are
preferentially recommended for persons aged ≥65 years when available
–Recipients should receive an age -appropriate influenza vaccine (one approved for
their age), with the exception that solid organ transplant recipients aged ≥18 years who are taking immunosuppressive medications regimens may receive either high- dose or adjuvanted inactivated vaccines (without preference over
other appropriate influenza vaccines)
Recommendations concerning timing, vaccine selection, and
contraindications and precautions remain the same as previouslySeasonal Influenza Vaccine Recommendations, 2025 -26
9 MMWR 2024;73(RR- 5):1-25
The 2025 -26 recommendations include three updates, all of which
reflect recent FDA approvals:
–Influenza vaccine composition for the 2025 -26 season
–FluMist (live attenuated influenza vaccine, trivalent; LAIV3) for self - or caregiver
administration
–Change in age indication for Flublok (recombinant influenza vaccine, trivalent;
RIV3) from ≥18 years to ≥9 yearsRecommendations for 2025 -26: Updates
10
All influenza vaccines marketed in the United States for the 2025 -26
season will be trivalent
U.S. influenza vaccine composition for 2025 -26 includes an update to
the influenza A(H3N2) component:
–AnA/Victoria/4897/2022 (H1N1)pdm09 -like virus for egg -based vaccines
or an A/Wisconsin/67/2022 (H1N1)pdm09 -like virus for cell and recombinant
vaccines;
–An A/Croatia/Y10136RV/2023 (H3N2)- like virus for egg -based vaccines
or an A/District of Columbia/27/2023 (H3N2) -like virus for cell and recombinant
vaccines;
–A B/Austria/1359417/2021 (B/Victoria lineage)- like virusU.S. Influenza Vaccine Composition for the 2025 -26
Influenza Season
Influenza Vaccine Composition for the 2025 -2026 U.S. Influenza Season | FDA 11
Approved by FDA in September 20241; presented to ACIP in April 2025
Anticipated to be available for the 2025 -26 influenza season
Consumers will be able to order FluMist  for delivery for eligible
recipients
–Screening for eligibility performed by central pharmacy, based on ACIP criteria
–Approved for self- administration for persons aged ≥18 years, or by a caregiver
aged ≥18 years for recipients aged 2 through 17 years
LAIV3 will continue to be available for administration by healthcare
providers as previously
No changes made to recommendations regarding appropriate populations, contraindications, or precautionsFluMist (LAIV3) for Self-  or Caregiver Administration
12 1.https://www.fda.gov/vaccines -blood -biologics/vaccines/flumist
Approved by FDA in March 20251
Previously approved for ≥18 years; new age indication is ≥9 years
Information has been updated in the Table of available U.S. influenza
vaccines for 2025 -26Approval of Flublok (RIV3) for Persons Aged 9 through 17
Years
1.https://www.fda.gov/vaccines -blood -biologics/vaccines/flublok 13
For more information, contact CDC
1-800- CDC- INFO (232 -4636)
TTY:  1 -888 -232-6348    www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official
position of the Centers for Disease Control and Prevention.
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation
use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.
14

Summary: U.S. Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. 2024 -25 Influenza Season Update and Seasonal Influenza  Vaccine Recommendations for the 2025 -26 U.S. Influenza  Season Dr. Vivien Dugan Influenza Division,…