Document text
Proposed clinical considerations for
clesrovimab
Advisory Committee on Immunization Practices
April 16, 2025U.S. Centers for Disease Control and Prevention
Jefferson Jones MD MPH FAAP
Co-Lead, Maternal/Pediatric RSV Work Group
•Similarities and differences in use of clesrovimab vs nirsevimab
•Review of indications, timing, and dosing
•Storage, handling, and administrationOutline
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Active and Passive Immunity
Chapter 1: Principles of Vaccination | Pink Book | CDC•Antibodies produced by own immune
system
•After being exposed to a disease -causing
organism, through
−Infection
−Vaccination
•Protection takes time to develop but is
often long -lasting •Antibodies produced externally
•Antibodies are transferred to a recipient
−Maternal antibodies across the placenta to
fetus
−Transfusion of blood products
−Receipt of antibody products
•Provides immediate protection, but wanesPassive Immunity Active Immunity Acquired Immunity
•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 nirsevimab 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
5
•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 6
*Clesrovimab is not currently approved by FDA or recommended by ACIPProposed Recommendations for Use
ofRSV Antibody Immunizations
(nirsevimab or clesrovimab *) in Infants
•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 Mothers
RSV Immunization Guidance for Infants and Young Children | RSV | CDC | ICU: intensive care unit
•For infants born October through March
-Administer in the first week of life —ideally during the birth hospitalization .
-Infants with prolonged birth hospitalizations due to prematurity or other
causes should be immunized shortly before or promptly after discharge.
-If not given in the hospital, administer in outpatient settings.
•For infants born April through September
-Optimal timing is shortly before the RSV season begins
(i.e., October through November)Timing of Infant RSV Antibody Administration
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 ; Beyfortus Prescribing Information (fda.gov)
October
November
December
January
February
March
April
May
June
July
August
SeptemberInfant RSV Antibody Timing by Birth Month:
First RSV Season in Most of Continental U.S.
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 ,
1 Most infants born to vaccinated mothers are not recommended to receive an RSV antibody
Infants1 born April through September are
recommended to receive an RSV antibody shortly
before the RSV season begins.Infants1 born October through March are
recommended to receive an RSV antibody within one
week of birth, ideally during 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 C ommittee 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.
Seasonal Administration Exceptions
RSV Immunization Guidance for Infants and Young Children | RSV | CDC•Recommendations for the timing of
infant RSV antibody administration are
flexible
•Health care providers may use clinical
judgment to determine when to give
infant RSV antibodies outside of
October through March.
•Special circumstances to consider:
-Travel to areas with increased RSV activity
-Concern that patient may not return for a
visit when RSV antibodies should ideally
be administered
•Recommended that CDC provide national recommendations with flexibility for state
and local jurisdictions but avoid providing region -specific recommendations due to
the complexity of implementation
•Supported current CDC recommendations on flexibility, but desired additional
guidance on how to support decisionmakers for implementing flexibility
•Making annual changes to the timing of RSV antibody administration would be
complicated for jurisdictions and providers
-Before 2020, the RSV season was fairly predictable with only minor year -to-year
variations. RSV seasonality appears to be returning to pre -pandemic patterns, but
additional years of data are needed to verify this
-Since real -time RSV data trends can be difficult to interpret, state or local
jurisdictions may also choose to alter the timing of RSV antibody administration
based on local historical patterns of RSV seasonalityWork group considerations on RSV antibody
administration flexibility
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•Not all RSV disease can be prevented, and for most of the Unites States,
administration of RSV antibody to newborns during October through March will
protect infants in their first few months of life during the peak of the RSV season
•There is no evidence -based test positivity threshold above which RSV antibody is
recommended
-3% is used to define the RSV season for surveillance purposes using the National
Respiratory and Enteric Virus Surveillance System (NREVSS) PCR test positivity
-3% is not a threshold to guide RSV antibody administration
•Use of local RSV data may be the best source to guide action
-Test positivity can differ by system based on testing practices and patient population
-Other sources of data, including trends in RSV hospitalizations or the total numbers of
positive tests can be consideredWork group considerations on RSV antibody
administration flexibility (2)
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•Potential advantages
-Can provide more time for infants to receive an RSV antibody prior to the start of
the RSV season
-Potentially useful for jurisdictions with early seasonality
•Potential disadvantages
-Protection is expected to be greatest shortly after administration and decrease
over time, but it is unknown how quickly protection decreases
-Infants who receive an antibody in September could have reduced protection by
the peak of the season and towards the end of the seasonConsiderations for starting RSV antibody
administration prior to October
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•Potential advantages
-Infants born in April could be immunized shortly after birth, providing protection
during their first few months of life when they are highest risk for severe disease
•Potential disadvantages
-The risk of exposure and infection during the tail end of the RSV season might be
low
-Most infants born to unvaccinated mothers are recommended to receive only
one dose of an RSV antibody
-Most infants who receive a dose in April would not be recommended to receive a
dose in October; a dose in October could provide protection for an entire RSV
seasonConsiderations for extending RSV antibody
administration past March
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•Because the timing of the onset, peak, and decline of RSV activity varies
geographically, public health authorities or regional medical centers may
provide additional guidance for infant RSV antibody administration for their
jurisdictions or patient populations
•In areas with clear increases in RSV transmission prior to October,
administration prior to October can be considered
•In areas with high RSV transmission through the end of March,
administering to newborns past March can be considered
•In areas with historical data suggesting consistent RSV transmission
beginning prior to October or consistent high RSV transmission past the end
of March, the standard months of seasonal administration can be modified
according to expected annual patternsConsiderations for administration of infant RSV
antibody outside of October through March
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Choose One Product to Prevent Severe RSV Disease in Infants
Most infants will not need both maternal vaccination and an RSV antibody.
*Proposed: clesrovimab is not currently approved by FDA or recommended by ACIP
Maternal RSV vaccination
- Pfizer AbrysvoInfant RSV antibody
-Nirsevimab
-Clesrovimab*- or -
Maternal
RSV vaccine
Infant RSV
antibodyImmediate protection for baby after birth
No injection for the infant
Potentially reduced protection in some situations (e.g., mother is
immunocompromised or infant born soon after vaccination)
Potential risk for hypertensive disorders of pregnancy
Direct receipt of antibodies rather than relying on transplacental transfer
Protection may wane more slowly than maternal RSV vaccine
Side effects are usually mild and resolve quickly; hypersensitivity reactions are
uncommon but have been reported
Delayed administration could leave the infant unprotected1
1 Infants born during October through March should be administered RSV antibody in the first week of life – ideally during the bir th hospitalization.
Use of the Pfizer Respiratory Syncytial Virus Vaccine During Pregnancy for the Prevention of Respiratory Syncytial Virus –Associa ted Lower Respiratory Tract Disease in Infants: Recommendations of the
Advisory Committee on Immunization Practices — United States, 2023 | MMWR ; Evaluation of Preterm Birth and SGA at Birth - October 2024 ACIP meeting
Considerations for Counseling Patients Regarding
Maternal RSV Vaccine and Infant RSV Antibodies
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
*Proposed: clesrovimab is not currently approved by FDA or recommended by ACIP
Infant RSV Antibody Administration
Beyfortus Prescribing Information (fda.gov)•Route
-Intramuscular injection
•Site
-Vastus lateralis muscle of anterolateral thigh
-The gluteal muscle should not be used.
•Coadministration
-Simultaneous administration with vaccines is
acceptable.
Expected Clesrovimab Storage and Handling*
*Not final as clesrovimab has not yet been approved. It is expected that storage and handling of clesrovimab will be similar the requirements of nirsevimab ; Nirsevimab Package Insert (fda.gov)
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.
Administer the Correct RSV Immunization Product
Infant RSV antibody
onlyInfants and Some
Young Children
Abrysvo 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 is not currently approved by FDA or recommended by ACIP
•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 necessaryProposed Recommendation on How 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.