05 MacNeil Mat Peds RSV 508

CDC ACIP — Vaccine Advisory Committee

Acip

Slides

51

Document text

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CDC RSV- NET, unpublished data. 4) Thompson et al, JAMA (2003): https://doi.org/10.1001/jama.289.2.179 5) Matias et al, Influenza Other Respi Viruses (2014): 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 
  
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   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 
  
   
  
   
  
   
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     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