Mening 04 Crowe 508

National Center for Immunization & Respiratory Diseases
Work Group Interpretation of Pfizer’s
MenABCWY Vaccine Clinical Trials Data
Sam Crowe, PhD, MPH
Meningococcal Vaccines Work Group Lead
February 23, 2023

              Policy Questions for Each Pentavalent Vaccine
 Should the pentavalent vaccine be included as an option for
MenACWY/MenB vaccination in people currently recommended to receive both vaccines?
– For e
xample, 16 year olds1
 Should the pentavalent vaccine be included as an option for people currently recommended to receive MenACWY only?
– For e
xample, 11–12 year olds
 Should the pentavalent vaccine be included as an option for people currently recommended to receive MenB only?
– For e
xample, during a serogroup B outbreak
116 year olds who decide to receive the MenB vaccine based on shared clinical decision-making 2

    Pfizer MenABCWY Vaccine and Trials Overview
 Comprised of Nimenrix (serogroups ACWY) and Trumenba (serogroup B)
– Trumenba currently licensed and available in US, 10y through 25y
– Nimenrix not licensed in US but used extensively elsewhere, 6w and older
 Two clinical trials completed (NCT03135834, NCT04440163)
– Assessed safety and immunogenicity of pentavalent vaccine
– Compared to Trumenba (MenB) and Menveo (MenACWY)
– Included participants 10 through 25 years of age
– Studied single and two dose (0, 6m) schedules
– 4-year persistence and booster dose were evaluated
 Extended interval study underway (NCT04440176)
– Study arm 1 — 0, 12m (data available)
– Study arm 2 — 0, 36m
3

          Safety
 Assessed by monitoring for and comparing local reactions, systemic events,
medically attended adverse events, serious adverse events, and newly diagnosed chronic medical conditions
 Local reactions within 7 days after vaccination
– Includes pain, redness, swelling
– Comp
arison between pentavalent and MenB vaccine only
– Slig
htly higher percentage of participants had a local reaction to pentavalent vaccine for
both 1st and 2nd doses
 Systemic events within 7 days after vaccination
– Includes fatigue, headache, muscle pain, joint pain, chills, diarrhea, vomiting, fever
– Simi
lar percentage of participants experienced systemic events in pentavalent vaccine
group and in MenACWY+MenB group
– Perc
entage varied slightly between groups by systemic event and by dose
4

         Safety, Continued
 Medically attended adverse events
– Sim
ilar percentages between study groups (both <15%)
 Serious adverse events
– Mor
e reported for pentavalent group (0.4% vs. 0%)
– Non
e assessed to be related to pentavalent vaccine (e.g., hospitalization due to other
medical conditions)
 Newly diagnosed chronic medical conditions (NDCMC)
– Mor
e reported for pentavalent group (1.1% vs. 0.3%)
– Hig
her number of participants with attention-deficit/hyperactivity disorder (ADHD) in
pentavalent group – most with related symptoms before entering study
 Higher risk patients (e.g., complement deficiency) not included in trials
5

          Immunogenicity Standards
 Serogroups A, C, W, and Y
– Percen
tage of participants achieving MenACWY seroresponse in hSBA
titer 1 month after 1 dose and 1 month after 2 doses
– Seroresponse is defined as a 4-fold increase in titer over baseline
 Serogroup B
– Perc
entage of participants achieving MenB seroresponse in hSBA 1
month after 2 doses
– Composite response provided
– Seroresponse is defined as a 4-fold increase in titer over baseline
6

Immunogenicity for Serogroups A, C, W, Y
 1 dose of the pentavalent vaccine is noninferior to 1 dose of MenACWY in both
ACWY-naïve and ACWY-primed participants 1 month after administration
ACWY-Naive ACWY-Primed
7

           Immunogenicity for Serogroups A, C, W, Y
 2 doses of the pentavalent vaccine given 6 months apart are noninferior to 1 dose
of MenACWY in both naïve and primed participants 1 month after administration
ACWY-Naive ACWY-Primed
8

            Seroprotection for ACWY-Naïve Participants after 4 Years
 Seroprotection persists up to 4 years in naïve participants after a 2-dose series
9

            Seroprotection for ACWY-Primed Participants after 4 Years
 Seroprotection persists up to 4 years in primed participants after a 2-dose series
10

       Immunogenicity for Serogroup B
 2 doses of the pentavalent vaccine given 6 months apart are noninferior to 2 doses
of MenB in naïve participants (primed not assessed)
11

        Seroprotection for Serogroup B-Naïve Participants
 Waning of immunity for the pentavalent vaccine is very similar to that observed
with MenB, dropping substantially by 12 months post-dose 2
12

           Additional Work Group Reflections
 Data not presented on 3-dose schedule of pentavalent vaccine
–
 3
-dose schedule of Trumenba currently recommended for certain
high-risk groups (e.g., people affected by a serogroup B outbreak)

 Data not available in people older than 25 years
–
 M
enB vaccines licensed for 10–25 years
–
 M
enACWY vaccines licensed up to 55 years or older depending on
vaccine
13

     Final Reflections and Next Steps
 Pfizer’s MenABCWY vaccine appears to be noninferior to MenACWY+MenB based
on clinical trial data presented

 Data gaps
–
 3-dose schedule for high-risk populations
– Adults older than 25 years

 Next steps
–
 Reviewing additional immunologic persistence data for a single dose
– GRADE and EtR — will focus on pentavalent vaccine studies
– Cost effectiveness study will be conducted
14

   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: National Center for Immunization & Respiratory Diseases  Work Group Interpretation of Pfizer’s  MenABCWY Vaccine Clinical Trials Data  Sam Crowe, PhD, MPH  Meningococcal Vaccines Work Group Lead  February 23, 2023                                                                                Policy Questions for Each Pentavalent Vaccine   Should the pentavalent vaccine be included as an option for  MenACWY/MenB vaccination in people currently recommended to receive both…


Polio 01 Brooks 508

Centers for Disease Control and Prevention
National Center for Immunization and Respiratory DiseasesCenters for Disease Control and Prevention
National Center for Immunization and Respiratory DiseasesCenters for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
ACIP Polio Vaccination Work Group
Oliver Brooks, MD, FAAP
ACIP Meeting February 23, 2023
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.

   Polio Vaccination Work Group Terms of Reference
Policy topics under consideration:
1) Whether more specific guidance on adult vaccination , including use of adult
booster doses, can be provided in the context of circulating poliovirus.
2) Whether adults who are immunocompromised should be recommended an
additional adult booster of a polio-containing vaccine.
3) Whether fractional doses of IPV (fIPV), as prequalified by WHO, should m eet polio
vaccination requirements, including for people immigrating to the United States.
4) Consider criteria under which novel Oral Polio Vaccine type 2 (nOPV2) might be
used in areas with outbreaks or persistent circulation of poliovirus.

Summary: Centers for Disease Control and Prevention National Center for Immunization and Respiratory DiseasesCenters for Disease Control and Prevention National Center for Immunization and Respiratory DiseasesCenters for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention  National Center for Immunization and Respiratory Diseases  ACIP Polio Vaccination Work Group  Oliver Brooks, MD, FAAP  ACIP Meeting February 23, 2023 …


Polio 02 Kidd 508

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NNN Naaaatttti iiio ooonn nnaaaallll    CC CCeeeennnnttt tee eerrrr    ffffoooorrrr    II IImmmmmm mmuuuunnnni iiiz zzza aaat ttti iiio ooonn nn    aaaann nndddd    RR RReeeespsp spspiii ir rrra aaattttoo oorrrryyyy    DDDDiiiisese sesea aaase sesesess ss
Adult Polio Vaccination
Sarah Kidd, MD, MPH
ACIP Meeting February 23, 2023
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.

      Objectives for Today’s Presentation
 Briefly summarize work group deliberations on adult polio vaccination
 Present proposed language for adult polio vaccination (anticipate ACIP
vote in June)
 Solicit feedback and identify areas where more data are needed prior to an ACIP vote

      2000 Recommendations for Inactivated Polio Vaccine (IPV)
Vaccination of Adults
 Vaccination is recommended for certain adults who are at greater risk for exposure
to polioviruses than the general population
 Unvaccinated adults who are at increased risk should receive a primary vaccination series with IPV
 Adults who have had a primary series of OPV or IPV and who are at increased risk can receive another dose of IPV
Poliomyelitis Prevention in the United States (cdc.gov)

      2000 Statement on IPV Vaccination for Adults
Questions and problems that came up in 2022
 2000 statement focused on adults atincreased risk of poliovirus exposure
 Unclear how to define increased risk in setting of circulating vaccine-derived
poliovirus (cVDPV) in US
 Unclear recommendation for unvaccinated adults who were not considered at
increased risk of exposure
 Unclear recommendation for vaccinated adults and when/if a booster was advised
Poliomyelitis Prevention in the United States (cdc.gov)

             Policy Question #1 for Work Group
 Should completion of a primary polio vaccination series with IPV be recommended
for unvaccinated and incompletely vaccinated adults in the US?
– Population: Unvaccinated and incompletely vaccinated (with OPV or IPV) US adults aged >18 years
– Intervention: Completion of a primary vaccination series with IPV
– Comparison: No vaccination or partial series completion
– Outcomes:
• Prevention of paralytic poliomyelitis
• Serologic immunity to poliovirus types 1, 2, and 3
• Serious adverse events following vaccination
• Indirect effects, e.g., community transmission, impact on health systems

      Current Definition of Fully Vaccinated
An adult is considered fully vaccinated if they received:
–
–
– A primary series of ≥3 doses of trivalent OPV (tOPV) or IPV in any combination
administered ≥4 weeks apart
AND
The last dose in the series was given on or after the 4th birthday
AND
The last dose in the series was given ≥6 months after the previous dose
Poliomyelitis Prevention in the United States (cdc.gov )

       Public Health Problem
 Poliovirus infection can cause
poliomyelitis and lifelong paralysis
– Paralytic disease occurs in <1% of
infections (varies by serotype)
– Non-paralytic clinical illness occurs in ~25%, including 1%–5% with aseptic meningitis
– Approximately 75% of infections are asymptomatic

   1950
1960
1970
1980
1990
2000
2010
2020Number of poliomyelitis cases 20000
15000
10000
5000
0 Paralytic polio decreased rapidly in the US after
introduction of polio vaccine
25000
1994: Americas
certified polio-free 1955: Salk IPV
1961: Sabin OPV 1979: Last indigenous
Wild-type case in US
2000: IPV only 1997: Sequential enhanced-potency
IPV followed by OPV 1952
1954 1956 1958
1962
1964 1966 1968
1972
1974
1976 1978
1982
1984
1986
1988
1992
1994
1996
1998
2002
2004 2006 2008
2012
2014 2016 2018
Year

   Global Paralytic WPV1 and cVDPV Cases1, Previous 12 Months2
WPV1 cases (latest onset)
Pakistan 20 15-Sep-22
Afghanistan 1 29-Aug-22
Mozambique 8 10-Aug-22
cVDPV1 cases (latest onset) DR Congo 92 16-Dec-22 Malawi 4 01-Dec-22 Mozambique 19 20-Nov-22
Madagascar 11 25-Sep-22
cVDPV2 cases (latest onset) Indonesia 2 03-Jan-23 CAR 5 26-Dec-22
Algeria 3 13-Dec-22 DR Congo 260 10-Dec-22 Yemen 121 02-Dec-22 Chad 36 11-Nov-22
Sudan 1 31-Oct-22 Cameroon 2 30-Oct-22 Niger 13 27-Oct-22
Nigeria 29 27-Oct-22 Mali 1 26-Oct-22
Benin 10 09-Oct-22
Togo 1 30-Sep-22
Ghana 3 14-Sep-22 Somalia 4 23-Aug-22
USA 1 20-Jun-22
Ethiopia 1 01-Apr-22
Mozambique 4 26-Mar-22 Eritrea 1 02-Mar-22
cVPDV3 case (latest onset)
Israel 1 12-Feb-22
Polio Now – GPEI (polioeradication.org )

      Paralytic Polio Case in New York State, July 2022
• A case of paralytic polio caused by vaccine-derived poliovirus type 2 (VDPV2) was
confirmed in an unvaccinated young adult from Rockland County, New York, on July 21, 2022
• Genetic sequencing has indicated a linkage to polioviruses collected in wastewater in Israel, United Kingdom, and Canada
• Rockland County has reported overall low vaccine coverage for over 20 years
• In summer 2022, 60% of children under 2 yrs of age had received the recommended 3 doses of IPV (zip code level as low as 37%)
• No additional paralytic cases have been identified

        Wastewater Testing for Poliovirus
 Poliovirus type 2 genetically linked to the case detected
in wastewater samples in New York (Rockland, Orange, Sullivan, and Nassau counties and New York City)
 Retrospective testing detected poliovirus as early as April 2022
 Most recent positive sample was collected on December 15, 2022; no detections in samples collected in last 7 weeks
 No additional paralytic polio cases identified

       –Seroprevalence of Poliovirus Antibodies by Age,
United States NHANES Serosurvey, 2009–2010
Percent positive (95% Confidence Interval)
Birth years Age in 2009 2010 Poliovirus Type 1 Poliovirus Type 2 Poliovirus Type 3
1998–2004 6–11 years 97.2 (94.7–98.8) 98.0 (96.4–99.0) 93.8 (91.8–95.4)
1990–1998 12–19 years 94.7 (92.0–96.6) 98.2 (96.6–99.2) 84.3 (81.0–87.2)
1970–1990 20–39 years 92.7 (90.0–94.2) 96.9 (95.2–98.2) 78.6 (74.6–82.2)
1960–1970 40–49 years 93.9 (91.6–95.7) 95.8 (93.8–97.3) 85.8 (82.3–88.8)
Source: Wallace et al, BMC Public Health 2016.

            Effectiveness of Enhanced-Potency IPV
 Presence of detectable neutralizing antibody is a correlate of protection against
paralytic disease.
– Immunity against paralytic disease may be present even in absence of detectable antibodies.
 Serologic immunogenicity among infants and children1
– 70%–100% seropositive after 2 doses
– 88%–100% seropositive after 3 doses
 Estimates of vaccine effectiveness against paralytic polio2
– 36%–89% for 1 dose
– 89%– 98% for 2 doses
 Paucity of data on adults receiving a primary series
1. Vidor et al review, PIDJ 1997.
2. Stoeckel et al, Rev Infect Dis 1984. CDC, MMWR 1988. John, Rev Med Virol 1993.

                 IPV and Mucosal Immunity
 Intestinal immunity1
– No significant difference between IPV and unvaccinated individuals in the odds of shedding
– IPV vaccination appears to reduce the mean quantity of shed poliovirus by 63%–91%
– Some data to suggest that IPV vaccination reduces duration of shedding ;recent modeling study
indicated no impact of IPV
 Nasopharyngeal (NP) immunity2
– Evidence to suggest similar, low rates of NP shedding (0%–4%) among OPV and IPV vaccinees
Sources:
1. Hird and Grassly meta-analysis, PLoS Pathogens 2012.
2. Kok et al, Bulletin of WHO 1992. Onorato et al, JID 1991. Brouwer et al, J R Soc Interface 2022.

                       Safety: IPV is well-tolerated.
 Local reactions at injection site reported in trials
– Tenderness in 14%–29%
– Induration in 3%–11%
– Erythema in 0.5%–1.4%
 Combining IPV with other vaccines is not associated with increased frequency or
severity of reported adverse reactions compared with the other vaccines alone
 No severe adverse events have been causally associated with use of the current formulation of IPV
Sources: Sanofi Pasteur Package Insert - IPOL (fda.gov) . Vidor et al, PIDJ 1997. Murdin et al, Vaccine 1996. Wattigney et al, Pediatrics 2001. IOM 1994.

       Vaccine Adverse Event Reporting System (VAERS) Data,
2000–2012
 >250 million IPV-containing vaccine doses distributed 2000–2012
 41,792 adverse event reports submitted for IPV-containing vaccines
– 34,880 (88%) were for non-serious events
– 95% were among persons <7 years of age
 Most events were associated with IPV co-administered with other vaccines
 Standalone IPV accounted for just 0.5% of reports
 VAERS is passive reporting system, cannot assess causal associations
 Reported adverse events were similar and proportional to other vaccines
Source: Iqbal et al, Lancet ID 2015.

   Considerations for a Risk-Based vs. Uniform
Recommendation for Unvaccinated Adults
Situations that put adults at increased risk of exposure
to poliovirus include:
 Travelers who are going to countries where polio is epidemic or
endemic (For additional information, see Polio: For Travelers).
 Laboratory and healthcare workers who handle specimens that
might contain polioviruses.
 Healthcare workers or other caregivers who have close contact
with a person who could be infected with poliovirus.
 Unvaccinated or incompletely vaccinated adults whose children
will be receiving oral poliovirus vaccine (for example, international
adoptees or refugees).
 Unvaccinated or incompletely vaccinated adults living or working
in a community where poliovirus is circulating.

   Considerations for a Risk-Based vs. Uniform
Recommendation for Unvaccinated Adults
Situations that put adults at increased risk of exposure
to poliovirus include:
 Travelers who are going to countries where polio is epidemic or
endemic (For additional information, see Polio: For Travelers). • Individual-level;
 Laboratory and healthcare workers who handle specimens that • Opportunity  to
anticipate  risk an d
vaccinate  prior  to
potential  exposure  might contain polioviruses.
 Healthcare workers or other caregivers who have close contact
with a person who could be infected with poliovirus.
 U nvaccinated or incompletely vaccinated adults whose children
will be receiving oral poliovirus vaccine ( for example, international
adoptees or refugees).
 Unvaccinated or incompletely vaccinated adults living or working
in a community where poliovirus is circulating.

   Considerations for a Risk-Based vs. Uniform
Recommendation for Unvaccinated Adults
Situations that put adults at increased risk of exposure
to poliovirus include:
 Travelers who are going to countries where polio is epidemic or
endemic (For additional information, see Polio: For Travelers).
 Laboratory and healthcare workers who handle specimens that
might contain polioviruses.
 Healthcare workers or other caregivers who have close contact
with a person who could be infected with poliovirus.
 Unvaccinated or incompletely vaccinated adults whose children
will be receiving oral poliovirus vaccine (for example, international • Population-level;
• Group already at
increased risk at time risk is recognized;
• Potential missed opportunities for
adoptees or refugees). vaccination prior to
 Unvaccinated or incompletely vaccinated adults living or working exposure in a community where poliovirus is circulating.

    Pros and Cons of a Uniform Recommendation for
Unvaccinated and Incompletely Vaccinated Adults
Pros:
 Allows unvaccinated adults and their health care providers to take advantage of
opportunities to get vaccinated before they are at increased risk of exposure
 Brings adult polio vaccination policy closer in line with other routine childhood vaccines, e.g., MMR and varicella vaccines
 Is less complicated policy to communicate and understand (i.e., recommendation doesn’t change based on latest wastewater data)

    Pros and Cons of a Uniform Recommendation for
Unvaccinated and Incompletely Vaccinated Adults
Cons:
 Most adults in the United States have a low risk of poliovirus exposure and paralytic
polio, and most adults received primary polio vaccination series as children
 Demand for IPV could potentially exceed supply, particularly if a large number of adults without documentation of polio vaccination status assume they were not vaccinated
– However, this issue can be mitigated by providing guidance for this group in the clinical
considerations

 Proposed Language for Unvaccinated and Incompletely
Vaccinated Adults
 Majority of work group believe pros of uniform recommendation outweigh cons;
approximately 1/3 favor maintaining the current risk-based recommendation
Majority Recommendation :
Adults who are known or suspected to be unvaccinated or incompletely vaccinated against polio should complete a primary vaccination series with IPV.
Clinical Considerations :
In general, unless there are specific reasons to believe they were not vaccinated, most
adults who were born and raised in the United States can assume they were vaccinated against polio as children.

             Policy Question #2 for Work Group
 Should a booster IPV dose be recommended for adults in the US who have
previously completed a primary polio vaccination series?
– Population: US adults aged >18 years who have completed a primary polio vaccination series (with
trivalent OPV, IPV, or a combination of both)
– Intervention: Booster dose of IPV
– Comparison: Adults who completed a primary series but did not receive a booster dose
– Outcomes:
• Prevention of paralytic poliomyelitis
• Serologic immunity to poliovirus types 1, 2, and 3
• Serious adverse events following vaccination
• Indirect effects, e.g., community transmission, impact on health systems

     Boosters: 2000 Statement and Rationale
 2000 Statement: “ Adults who have had a primary series of OPV or IPV and who are
at increased risk can receive another dose of IPV. Available data do not indicate the
need for more than a single lifetime booster dose with IPV for adults .”
 Rationale
– Longstanding recommendation since tOPV was used in routine immunization
– Actual need for supplementary dose not established, but “there is value in assuring protection
against infection with wild polioviruses when exposure can reasonably be expected.” (1977 ACIP Statement)
– At least 2 reported cases of paralytic polio in adult travelers who had completed a primary vaccination series with Salk IPV and/or tOPV
CDC MMWR 1977; CDC MMWR 1986.

            –Unclear Need for IPV Booster in Vaccinated Adults:
Seroprevalence of Poliovirus Antibodies by Age, United States
NHANES Serosurvey, 2009–2010
Percent positive (95% Confidence Interval)
Birth years Age in 2009 2010 Poliovirus Type 1 Poliovirus Type 2 Poliovirus Type 3
1998–2004 6–11 years 97.2 (94.7–98.8) 98.0 (96.4–99.0) 93.8 (91.8–95.4)
1990–1998 12–19 years 94.7 (92.0–96.6) 98.2 (96.6–99.2) 84.3 (81.0–87.2)
1970–1990 20–39 years 92.7 (90.0–94.2) 96.9 (95.2–98.2) 78.6 (74.6–82.2)
1960–1970 40–49 years 93.9 (91.6–95.7) 95.8 (93.8–97.3) 85.8 (82.3–88.8)
NOTE: Presence of detectable neutralizing antibody is a correlate of protection against paralytic disease.
Immunity against paralytic disease may be present even in absence of detectable antibodies.
Source: Wallace et al, BMC Public Health 2016.

 Benefits of IPV Booster
 No data on vaccine effectiveness of primary
series + booster vs. primary series only
 Serologic studies in adults with heterogeneous pre-booster vaccination histories/seropositivity: 98%–100% were
seropositive 1 month after an IPV-containing booster
 One study followed up trial participants 10 years post-booster: 98%–100% still seropositive Data from Grimprel et al, Vaccine 2005:
Seropositivity before and 1 month after IPV -
containing booster by study group and poliovirus serotype
Sources: Broderick et al, Vaccine 2015; Domenicus et al, Vaccine 2014; Fukushima et al, Vaccines 2022; Grimprel et al, Vaccine 2005; Kovac et al, Vaccine 2015; Larnaudie et al,
Human Vaccines 2010; Zimmermann et al, Vaccine 2013.

    Strong Majority of Work Group Agree with Current
Recommendation for Adult IPV Booster
 Risk-based
 Shared clinical decision-making
Proposed Language:
 Adults who have received a primary series of tOPV or IPV in any combination and
who are at increased risk of poliovirus exposure may receive another dose of IPV.
Available data do not indicate the need for more than a single lifetime booster dose with IPV for adults.

 Thank you to
 ACIP voting members
– Oliver Brooks (Chair)
– Lynn Bahta
 Liaisons the ACIP Polio Work Group Members
– Lynn Fisher, American Academy of Family Physicians
– Chandy C John, American Academy of Pediatrics
– Sandra Fryhofer, American Medical Association
– Kathy Kudish, Association of Immunization Managers
– Marcus Plescia, Association of State and Territorial Health Officials
– Paul R Cieslak, Council of State and Territorial Epidemiologists
– Christine Hahn, Council of State and Territorial Epidemiologists
– Tina Q. Tan, Infectious Diseases Society of America
– Adenike Shoyinka, Infectious Diseases Society of America
– Mary Wilson, International Society of Travel Medicine
– Jaqueline Lawler, National Association of County and City Health Officials
– Kathy Edwards, Pediatric Infectious Diseases Society
– Joseline Zafack, Public Health Agency of Canada
– Oliver Baclic, Public Health Agency of Canada
 Ex Officio
– Robin Levis, FDA
– Robin Wisch, FDA  Consultants
– Edwin Asturias
– Doug E Campos-Outcalt
– Emily Lutterloh
– Walt Orenstein
– Jennifer Rosen
– Eli Rosenberg
 CDC
– Achal Bhatt
– Stephanie Bialek
– Thomas Clark
– Kathleen Dooling
– Brian Edlin
– Concepcion Estivariz
– Halle Getachew
– Sarah Kidd
– Janelle King
– Elisabeth Krow-Lucal
– M. Steve Oberste
– Janell Routh
– Eileen Yee

         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.

Summary: CCCCenen enentt ttererer ers sss     f fffo ooorrr    r DiDi DiDiss sseaea eaeassssee e    e CCCCoooonnnnttt trrr roooollll     aaaannnndddd     PP PPrr rreeeevvvvenenenenttttiii iooo onnnn  NNN Naaaatttti iiio ooonn nnaaaallll    CC CCeeeennnnttt tee eerrrr    ffffoooorrrr    II IImmmmmm mmuuuunnnni iiiz zzza aaat ttti iiio ooonn nn    aaaann nndddd    RR RReeeespsp spspiii ir rrra aaattttoo oorrrryyyy    DDDDiiiisese sesea aaase sesesess ss  Adult Polio Vaccination  Sarah Kidd, MD, MPH  ACIP…


RSV Pediatric 01 Long 508

1
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Maternal/Pediatric Respiratory Syncytial Virus (RSV)
Work Group
Sarah S. Long, MD
Chair, Maternal/Pediatric RSV Work Group
ACIP General Meeting
February 23, 2023

2Work group members
ACIP Members
Sarah Long (chair)
Pablo SanchezOliver Brooks
Camille Kotton
Ex Officio Members
Rachel Zhang (FDA -CBER)
Nicholas Geagan (FDA -CBER)
Judy Beeler (FDA -CBER)
Yodit Belew (FDA -CDER)
Prabha Viswanathan (FDA -CDER)
Sonnie Kim (NIH -NIAID)
April Killikelly (Public Health Agency of Canada)
Winnie Siu (Public Health Agency of Canada)Valerie Marshall (OIDP/OASH)
Jessica Lee (CMS/CMCS)
Terry Dalle -Tezze (HRSA)Consultants
Cody Meissner (Dartmouth Geisel School of Medicine)Helen Chu (University of Washington)Natasha Halasa (Vanderbilt University)
Denise Jamieson (Emory University School of Medicine)
Daniel Feikin (World Health Organization)
Carol Baker (University of Texas Health Science Center)
Kevin Ault (Western Michigan University)
Liaisons
James McAuley (IDSA)
Patsy Stinchfield (NFID)
Brenna L. Hughes (ACOG)
Nicole Chaisson (AAFP)
Sean O’Leary (AAP)Jennifer Schuster (PIDS)
Molly Howell (AIM)CDC
Katherine Fleming -Dutra (co -lead)
Jefferson Jones (co -lead)
Meredith McMorrow
Mila Prill
Natalie Thornburg
Aron Hall
Ismael Ortega -Sanchez
Tamara Pilishvili
Melissa Coughlin
Jamison Pike
Lauren Roper
Amber Winn
Chris Taylor
GRADE/ EtRconsultants
Doug Campos -Outcalt
Rebecca MorganClaire Midgley
Fiona Havers
Tami SkoffAngie Campbell
Michael Melgar
Amanda PayneNicole Dowling
Noelle Molinari
Pragna Patel
Andrea Sharma
3Epidemiology and burden of RSV in infants
–RSV seasonality in United States
–Outpatient, emergency department (ED) visits, hospitalizations, and
deaths
Virology and immunology of RSV
Safety and efficacy of nirsevimab
–Phase 3 study in infants born ≥35 weeks gestation (initial and updated results)
1
–Phase 2b study in infants born 29 –34 weeks gestation
–Phase 2/3 safety and pharmacokinetic study in infants at high risk of RSV disease
2
1Initial results from start of trial until pause for COVID- 19 pandemic and updated
results that included entire sample. 2Eligible for palivizumab.Previous maternal/pediatric RSV ACIP presentations
4Agenda: Thursday February 23, 2023
Cost effectiveness analysis for nirsevimab –
CDC model
Cost effectiveness analysis for nirsevimab –
Comparison to manufacturer model
Evidence to Recommendations framework for
nirsevimab
Clinical considerations for nirsevimab
Safety and Efficacy of RSV Bivalent PreF
Maternal Vaccine
Workgroup considerationsDr. David Hutton (University of Michigan)
Dr. Ismael Ortega Sanchez (CDC)
Dr. Jefferson Jones (CDC)
Dr. Jefferson Jones (CDC)
Dr. Iona Munjal (Pfizer)
Dr. Katherine Fleming -Dutra
(CDC)
5

Summary: 1 Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Maternal/Pediatric Respiratory Syncytial Virus (RSV)  Work Group Sarah S. Long, MD Chair,…


RSV Pediatric 02 Hutton 508

Economic Analysis of
Nirsevimab in Pediatric
Populations
David W. Hutton, PhD, MS
Associate Professor, Health Management and Policy, School of Public Health
Associate Professor of Global Public Health, School of Public Health
Associate Professor, Industrial and Operations Engineering, College of Engineering
University of MichiganACIP General Meeting
February 23, 2023

Research Team
University of Michigan
•David Hutton, PhD
•Lisa Prosser, PhD
•Angela Rose, MPH
•Kerra Me rcon, MSCDC
•Jefferson Jones, MD, MPH, FAAP
•Mila Prill , MSPH
•Meredith McMorrow, MD, MPH, FAAP
•Jamison Pike, PhD
•Katherine Fleming-Dutra
•Ismael Ortega - Sanchez, PhD
•Fiona Havers, MD
•Betsy Gunnels, MSPH
7
Conflicts of interest statements
–Authors have no known conflict of interests.
8
Methods: Study question
•Determine the cost- ef fectiveness of nirsevimab by:
•Evaluating the population burden of disease in pediatric US
popul
ation in terms of
•annual resource utilization
•total cases
•total costs
•deaths
•quality- adj usted life years
•Comparing the incremental cost -ef fectiveness ratio of nirsevimab to
no prevention.
•Running scenario analyses outcomes that explore key areas of
unc
ertainty.
•Perspective: Societal
9
Methods: Intervention(s)
•Target population: US pediatric < 7 months of age entering their
f
irst RSV season
•Secondary analysis high-r isk infants in their second RSV season (7 -18
months old)
•Interventions:
1.No n irsevimab (Natural history)
2.Nirsevimab against RSV illness
•Time horizon: 1 RSV season
•Analytic horizon: lifetime
•Discount rate: 3%
10
Methods: Decision Tree Model
11No
Prophylaxis
NirsevimabInfection Hospitalization
ED
None of the aboveOutpatientAlive
DeadInfection
Adverse
EventsSystemic Reaction
Injection Site Reaction
None of the aboveSerious Adverse EventInfection Infection
Methods: Epidemiology
Hospitalization
12Base Case Range Source
Respiratory syncytial virus (RSV)
incidence, per 100,000 See Above See AboveCDC NVSN,
December 2016 to September 2020
Proportion with LRTI
Age 0-5 months 1.0 0.5-1.0 Rainisch, 2020
Age 6-11 months 1.0 0.5-1.0 Rainisch, 2020
CDC New Vaccine Surveillance Network (NVSN) hospitalization rates for children under 2 years of age from December 2016 to Septem ber 2020 - 1,000 2,000 3,000 4,000
0246810121416182022Hospitalization
rate  per 100,000
children
Age in months
Methods: Epidemiology
ED and Outpatient
13Respiratory syncytial virus
(RSV) incidence, per 100,000 Base CaseRange Source
Emergency Department
Age 0 -5 months 7,500 5,500 –7,500 Lively 2019 (base case and range)
5,
Hall 2009 (range)6
Age 6 -11 months 5,800 5,700 –5,800
Age 12 -23 months 3,200 3,200 –5,300 Hall 2009 (base case and range)6,
Lively 2019 (range)5
Proportion with LRTI
Age 0 -5 months 0.65 0.25- 1.0 Rainisch, 20204
Age 6 -11 months 0.5 0.25- 1.0 Rainisch, 20204
Medically attended outpatient
Age 0 -5 months21,60013,200 –
21,600Lively 2019 (base case and range)
5,
Hall 2009 (range)6
Age 6 -11 months24,60017,700 –
24,600
Age 12 -23 months18,4406,600 –29,620 Jackson 2021 (base case and
range)7, Hall 2009 (range)6
Proportion with LRTI
Age 0 -5 months 0.65 0.25- 1.0 Rainisch, 20204
Age 6 -11 months 0.3 0.1-1.0 Rainisch, 20204
Methods: Epidemiology
Mortality
14Base
CaseRange Source
RSV mortality per hospitalization
Age 0-5 months 0.04% 0.03-0.05% Doucette 2016
8
Age 6-11 months 0.04% 0.03-0.05%
Age 12 -23 months 0.3% 0.24% -
0.28%Gupta 201610
Seasonality
150.0%5.0%10.0%15.0%20.0%25.0%30.0%
AprMay Jun JulAug Sep OctNov Dec Jan Feb MarFraction of Annual Infections
Source: National Respiratory and Enteric Virus Surveillance System (NREVSS) (2015- 2019)
0.00%10.00%20.00%30.00%40.00%50.00%60.00%70.00%80.00%90.00%100.00%
0 2 4 6 8 10 12 14Efficacy
MonthMethods: Inputs
average 5-month efficacy
= trial efficacy
Sigmoid decay to
final efficacy
16Zero efficacy
Methods: Efficacy
17Variable Base
case
valueRange for
sensitivity
analysisSource
Nirsevimab
Initial efficacy
(months 1- 5) against
RSV-associated
LRTI 80.0% 68.5% -86.1%MELODY trial
and Phase 2b recommended dose
Efficacy months 6-
10 25.0% 0.0% -50.0%
Efficacy after 10 months
0.0%
Methods: Provision of Nirsevimab
•Base case:
–At birth for those born
•October 1 – M arch 31
–October for those born in
•April (~6 -m onth visit)
•June (~4- m onth visit)
•August (~2- m onth visit)
–November for those born in
•May (~6 -m onth visit)
•July (~4- m onth visit)
•September (~2- m onth visit)
18
Methods: Medical Costs
Variable Value Range Source
Disease-specific
hospitalization costs
(per hospitalization)
Age 0-11 months $11,487 11042 -11933
Bowser 2022Age 12- 23 months $11,469 11029 -11910
Disease-specific ED
costs (per ED visit)$563 544 –581 Bowser 2022
Disease-specific outpatient costs (per
outpatient visit)$82 46-118 Bowser 2022
19•Bowser, 2022 is a systematic review using studies from 2014-2021
•Funded by Sanofi
•All numbers updated to 2022 dollars using GDP Deflator
Methods: Productivity Costs
Variable Value Range Source
Productivity burden of
RSV Disease (caregiver
losses)
Days of lost productivity
Outpatient* 2.5 0-5Fragaszy, 2018; Petrie, 2016;
Van Wormer, 2017
ED* 2.5 0-5Fragaszy, 2018; Petrie, 2016; Van Wormer, 2017
Hospitalization^ 7.4 0-14
Lifetime productivity for those <1 year old (lost
from death)1,795,936 Grosse, 2019
20*Productivity for outpatient and ED based on adult influenza
^Hospitalization productivity loss = length of hospitalization + 2 days
Methods: Intervention Cost
Variable Value Range Source
Immunization-related
costs
Nirsevimab, per dose $300 $50-$600 Assumption
21
Methods: RSV
Health-Related Quality-of -Life
22LRTI quality adjusted life DAYS lost Base Lower (Regnier) Upper (JIVE)
Outpatient: Child 3.1 1.8 16.6
Outpatient: Caregiver 1.5 0 9.1
ED: Child 4.9 2.9 16.6
ED: Caregiver 2.5 0 9.1
Hospitalized: Child 6.2 3.7 26.5
Hospitalized: Caregiver 2.4 0 13.6Measured in
Days Lost
Most
Likely
Methods: Additional Inputs
•Also included nirs evimab adverse events
–Systemic reactions
–Injection site reactions
–Serious adverse events
–Medical costs
–Productivity costs
–Quality-adjust ed life- years lost
23
Methods: Uncertainty analyses
•One- w ay sensitivity
•Scenarios:
–Upper respiratory infection effect
–Timing of administration
•Additional Scenario:
–High-ri sk children entering the second RSV season
24
Results: Base Case
25•Base Case:
–Population of 1,000 births
–100% uptake in the nirsevimab group
–First RSV season
–$300/dose
–Nirsevimab only impacts LRTI
Results: Health Outcomes
26
Cohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group231
172
67 46
13 5  - 50 100 150 200 250
Natural History
Nirsevimab
Natural History
Nirsevimab
Natural History
Nirsevimab
Medically attended
outpatientEmergency
DepartmentInpatient
URTI LRTI
Results: Health Outcomes
27
Cohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group59
20.9
7.8
1.7 42.3
5.2
010203040506070
Outpatient ED Inpatient ICU Inpatient Day ICU DayEvents Averted per 1000 births
Results: Health Outcomes
28
Cohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group17 48 128 581
24 194
 - 100 200 300 400 500 600 700
Outpatient ED Inpatient ICU Inpatient Day ICU DayNumber needed to Prophylax to avoid
Results: Costs
29
Base cost of $300/doseCohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group $- $100,000 $200,000 $300,000 $400,000 $500,000 $600,000
Natural History
Nirsevimab
Natural History
Nirsevimab
Natural History
Nirsevimab
Natural History
Nirsevimab
Natural History
Nirsevimab
Natural History
Nirsevimab
Intervention Outpatient ED Inpatient Deaths Total
Medical Productivity
Results: Health Outcomes
30
Base cost of $300/doseCohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group$2,476 $6,950 $18,515 $84,158
$3,429 $28,053
 $- $10,000 $20,000 $30,000 $40,000 $50,000 $60,000 $70,000 $80,000 $90,000
Outpatient ED Inpatient ICU Inpatient Day ICU DayCost per Event Averted
Results: QALYs Lost
31Adverse
EventsOutpatient ED Inpatient Deaths Total Grand
Child Caregiver Child Caregiver Child Caregiver Child Child Caregiver Total
Natural
History 1.95 0.98 0.90 0.45 0.22 0.09 0.15 3.22 1.51 4.73
Nirsevimab 0.03 1.46 0.73 0.62 0.31 0.09 0.03 0.06 2.25 1.07 3.32
Cohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group
Results: Cost-Effectiveness
32Overall Costs QALYsICER
($/QALY)
Natural
History $ 357,151 4.73
Nirsevimab $ 502,077 3.32 $ 102,805
Base cost of $300/doseCohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group
Sensitivity: Tornado
33
Base cost of $300/doseCohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group Cost QALYs Efficacy$0 $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000
Nirsevimab cost/dose
Initial Efficacy
Proportion of Outpatient visits (age 0-5 months) with an LRTI
diagnosis
Proportion of hospitalizations (age 0-5 months) with an LRTI
diagnosis
Proportion of ED Visits (age 0-5 months) with an LRTI
diagnosis
Proportion of outpatient visits (age 6-11 months) with an LRTI
diagnosis
RSV child QALYs lost due to outpatient visit
RSV caregiver QALYs lost due to outpatient visit
RSV child QALYs lost due to ED visit
RSV caregiver QALYs lost due to ED visitIncremental Cost-Effectiveness Ratio ($/QALY)
Low High
 $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000
$0 $100 $200 $300 $400 $500 $600ICER ($/QALY)
Total Cost of Nirsevimab (drug + administration)Sensitivity: Cost
34 Cohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group
Scenario: Upper Respiratory Infection Effect
35Cohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group57
20.4
7.7
1.741.4
5.1108
33.5
7.7
1.741.4
5.1
020406080100120
Outpatient ED Inpatient ICU Inpatient Day ICU DayEvents Averted per 1000 birthsEvents Averted
Averted Base Averted URTIOnly Outpatient and ED
are impacted by upper respiratory impact
 $- $20,000 $40,000 $60,000 $80,000 $100,000 $120,000 $140,000
$0 $100 $200 $300 $400 $500 $600ICER ($/QALY)
Total Cost of Nirsevimab (drug + administration)Scenario: Upper Respiratory Infection Effect
36 Cohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group
Nirsevimab is assumed to be equally efficacious in preventing upper respiratory tract infections as lower respiratory tract infections.
Scenario: Timing Analysis
37•Cost-effectiveness of an infant receiving nirsevimab as a
newborn in
– Oct- Feb
– Oct- March
– Oct- April
•With varying efficacy in months 6- 10
–0%
–25%
–50%
Cohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group
38Scenario: Timing and Efficacy in
months 6 -10
Slightly Lower ICERs for Oct -MarBase cost of $300/doseCohort:1,000 nirsevimab and 1,000
natural history, assuming 100% uptake in nirsevimab group $- $20,000 $40,000 $60,000 $80,000 $100,000 $120,000
0% efficacy 25% efficacy 50% efficacyICER ($/QALY)
Oct-Feb Oct-Mar Oct-Apr
Scenario: Reduction in Palivizumab
39Overall Costs QALYsICER
($/QALY)
Natural
History $  418,551 4.73
Nirsevimab $  502,077 3.32 $  59,250
Base cost of $300/doseCohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group•Potential cost impact if clinicians choose to use n irsevimab in
palivizumab -eligible infants
•Savings assumptions:
–1.6% are high-risk (palivizumab-eligible)
–75% uptake in high-risk
–4.1 palivizumab doses/person on average
–$1,228/palivizumab dose
Higher -risk children entering the second
RSV season
40•Immunization in October (under 19 months old in
October)
•Incidence of RSV -associated hospitalization and mortality
per hospitalization:
–1x, 2x, 4x 6x, 10x higher
•Cost
–$600 nirsevimab costs (2x $300/dose)
–$1000 nirsevimab costs (2x $500/dose)
Cohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group
Second Season, High -Risk
41
Cohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group020406080100
Inpatient ICU Inpatient Days ICU DaysEvents Averted per 1000
ChildrenEvents Averted
Base 2x 4x 6x 10x
Second Season, High -Risk
42
Cost is per overall course, for 2 dosesCohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab groupICER by cost of nirsevimab
(product plus administration) ($/QALY)
Hospitalization and
Mortality rate$600 $1000
1x (base) $     815,051 $     1,410,155
2x $     449,238 $        800,666
4x $     145,014 $        282,945
6x $       53,061 $        122,409
10x $            404 $          27,390
Limitations
•Model Structure
–No risk groups
–No dynamic transmission. No impact of the vaccine on transmission and
in
direct effects
•Uncertain inputs
–Nirsevimab co st
–QALYs lost
–Upper respiratory tract infections
–Palivizumab utilization
43
Summary
•Nirsevimab m ay be cost -effective
•Results sensitive to:
–Cost per dose (Cost -S aving –316,000 $/QALY)
–Efficacy (75,000 -153,000 $/QA LY)
•URTI/LRTI
–Proportion of infections with LRTI
–Or efficacy of ni rsevimab against URTI
–QALYs lost (41,000 -125,000 $/QA LY)
•Hospitalization, Outpatient, ED
•Child, Parent
44URTI: Upper Respiratory Tract Infection
LRTI: Lower Respiratory Tract InfectionQALY: Quality -Adjusted Life -Year
Thank You
•Please send comments to:
•dwhutton@umich.edu
45

Summary: Economic Analysis of  Nirsevimab in Pediatric  Populations David W. Hutton, PhD, MS Associate Professor, Health Management and Policy, School of Public Health Associate Professor of Global Public Health, School of Public Health Associate Professor, Industrial and Operations Engineering, College of Engineering University of MichiganACIP General Meeting February 23, 2023  Research Team University of Michigan •David Hutton, PhD •Lisa Prosser, PhD •Angela Rose, MPH •Kerra Me rcon, MSCDC •Jefferson…


RSV Pediatric 03 Sanchez 508

Economics of Preventing Respiratory Syncytial
Virus Lower Respiratory Tract Infections (RSV-
LRTI) among US Infants with Nirsevimab
A SUMMARY REPORT COMPARING MODELS FROM:
Sanofi AND University of Michigan and CDC
Ismael R. Ortega -Sanchez, PhD
NCIRD/CDC
ACIP Meeting, February 23, 2023
46Disclaimer : The findings and conclusions in this report are those of the authors and do not necessarily represent the views of
the Centers for Disease Control and Prevention.
National Center for Immunization & Respiratory Diseases
Conflict of interest
•Sanofi model :  Alexia Kieffer et al., [complete authors list and
affiliations, upon request ]
•Sanofi manufactures nirsevimab
•Evidera (San Francisco, London) was funded by Sanofi
•UM-CDC model: David W Hutton et al. from Univ Michigan, …,
I
smael R Ortega -Sanchez et al. from CDC [complete authors list and
affiliations, upon request ]
•All authors: No conflicts of interest
47
Overview
Policy questions:
•Should one dose of nir sevimab be recommended
•a) at birth for all infants born during October to March a nd
•b) for all infants born during April through September and <8
m
onths of age when entering first RSV season?
•Should nirsevimab be recommended for children <20 months of age en
tering their second RSV season who remain at increased risk of
severe disease?
48
Economic analysis
Question: Is the use of nirsevimab against RSV LRTI in all infants <8 months
entering their first RSV season or born during season (and in high- risk children
<20 months entering the 2ndseason) cost-effective ?
Comparator Intervention
Base -case
 scenario: What is the incremental cost -effectiveness of using nirsevimab in all
infants <8 months entering their first RSV season or born during season (and in high- risk
children <20 months entering second season) relative to “Standard of Care”?
49Standard of care (SoC)
Infants in first season(and high-risk in 2
nd
season)Giving nirsevimab to
inf
ants in first season
(and hi
gh-risk in 2nd
season)
Standard of Care (SoC) = Palivizumab only for infants eligible as per AAP recommendations, and no immunization for all other pr e-term
and term infants
Focus on key features for model comparison
•Modeling approach
•Targeted population(s)
•Perspective (healthcare vs. societal)
•Intervention strategies and comparators
•Inputs for RSV disease burden, nirsevimab efficacy, and costs
•Incidence of RSV disease, rates of outcomes
•Direct and indirect costs of RSV disease
•Intervention: efficacy, duration of protection, safety and program costs
•Assumptions
•Strong, influential assumptions
50
51Modeling design and assumptions
Sanofi UM-CDC
Static analytical decision -making models ✔ ✔
Sensitivity analyses (and probabilistic simulation) ✔(✔) ✔
Hypothetical population: All infants < 8 months (high risk children 8-19
months)✔(✔) ✔(✔)
Time Frame: First year after a dose of nirsevimab
(2ndseason, 2nd dose for high-risk 8 -19 months only)✔
(✔)✔
(✔)
Analytic Horizon: two years or seasons (for temporary disability) and
Life Expectancy (for premature mortality)✔
✔✔
✔
Discount rate: 3% ✔ ✔
Year of economic outcomes measured: 2022 ✔ ✔
Societal perspective (and healthcare perspective) ✔(✔) ✔(✔)
52Inputs and main outcomes
Prevention of:
•MA RSV LRTI
•RSV LRTI hospitalizations
•RSV-associated deaths
QALYs saved$/QALY saved
Number needed to
immunize (NNI) to avert an:•MA RSV LRTI
•RSV LRTI hospitalization
•RSV-associated deathSanofi UM-CDC
✔ ✔
✔ ✔
✔ ✔
✔ ✔
✔ ✔
✔ ✔
✔ ✔
✔ ✔
HCRU = health care resource use, MA = Medically attended, LRTI= Lower respiratory tract infection, QALY= quality -adjusted life y ear

Sanofi model : Base case estimates for all infants <7
months in  Season 1, nirsevimab cost $500/dose & PSA
53Summary outcomes Base-Case
$/QALY gained $70,430
$/RSV MA LRTI case averted $798
$/RSV-associated LRTI
hospitalization averted $9,387
$/RSV-assoc. death averted >$5.6Million
NNI to avert an RSV-MA LRTI
case 5
NNI to avert an RSV-
associated LRTI hospitalization 43
NNI to avert a death 55,957
Probabilistic sensitivity analysis (PSA)
Base case

UM-CDC: Base case estimates for all infants <8
months, Season 1, nirsevimab cost $300/dose
54Cost per type of health outcome prevented Summary outcomes Base-Case
$/QALY gained $102,805
$/RSV-MA LRTI case averted $2,100
$/RSV-associated
LRTI hospitalization averted $18,881
$/RSV-assoc. death averted n/r
NNI avert an RSV -MA LRTI
case 14
NNI avert an RSV -assoc. LRTI
hospitalization 130
NNI avert an RSV -assoc. death n/r
Assuming 100% uptake in nirsevimab group
n/r = not reported$2,528 $7,096 $18,881 $85,822
$3,496 $28,607
 $- $10,000 $20,000 $30,000 $40,000 $50,000 $60,000 $70,000 $80,000 $90,000 $100,000
Outpatient ED Inpatient ICU Inpatient
DayICU DayCost per Event Averted
Sanofi and UM-CDC models comparison:
Selected outcome ratios for nirsevimab
55UM- CDC model
Price per dose $300Sanofi model
Price per dose $500
$ / QALY gained
nirsevimab Season 1, infants $102,805 $70,430
nirsevimab Season 2, high risk infants $842,139b$823,131a
nirsevimab Seasons 1 & 2 combined n/r $62,589
nirsevimab vs palivizumab, Season 2 PEPc n/r dominant
$ / hospitalization averted
nirsevimab Season 1 $18,881 $9,387
nirsevimab Seasons 1 & 2 combined n/r $8,316
a. Pre-t erm infants only
b. High risk <19 months old infants (preterm + PEP) receiving a 2nddose of nirsevimab in October
c. PEP= palivizumab eligible population
n/r = not reported
UM-CDC model : One-way Sensitivity Analyses (Season 1 only)
Base case: $102,805/QALY saved, nirsevimab cost $300/dose
56Assuming 100% uptake in nirsevimab group$0 $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000
Nirsevimab cost/dose
RSV QALYs lost Hospitalized RSV QALYS Lost
Initial Efficacy
RSV QALYs lost Outpatient Child
Proportion of RSV infections with an LRTI diagnosis Outpatient Age 0-5 months
RSV QALYs lost Outpatient Child caregiver
Proportion of RSV infections with an LRTI diagnosis Hospitalizations Age 0-5 months
Proportion of RSV infections with an LRTI diagnosis ED Visits Age 0-5 months
RSV QALYs lost ED  Child
Proportion of RSV infections with an LRTI diagnosis Outpatient Age 6-11 months
Low HighNirsevimab cost/dose
RSV QALYs lost by a child while hospitalized
Initial vaccine efficacy
RSV QALYs lost by an outpatient’s caregiver
Proportion of RSV infections with an LRTI diagnosis in outpatient visits (age 0 -5 months)
RSV QALYs lost by a child as an outpatient
Proportion of RSV infections with an LRTI diagnosis in hospitalizations (age 0 -5 months)
Proportion of RSV diagnosis in an LRTI diagnosis in ED visits (age 0 -5 months)
RSV QALYs lost by a child as ED patient
Proportion of RSV LRTI diagnosis in outpatients visits (age 6 -11 months)
Sanofi model : One-way Sensitivity Analyses (Season 1 only)
Base case: $70,430/QALY saved, nirsevimab cost $500/dose
57

Sanofi and UM-CDC models comparison:
Selected influential inputs
58•RSV-ho spitalization rate
Sanofi: Age and term -specific hospitalization rates reported in McLaurin (2016)a
UM-CDC: From RSV -associated hospitalization ratesbamong children aged ≤2 years
•Unitary medical cost of RSV hospitalization
Sanofi: Cost varies by term at birth and by whether Intensive Care Unit or Mechanical Ventilator were needed
as reported in McLaurin (2016)b
UM-CDC: Unit cost was a weighted average by term at birth and age as reported in Bowser (2022)c
•RSV season & intervention period
Sanofi: MA RSV season based on Rainisch (2020)dbut intervention ends in February
UM-CDC: RSV-season and intervention period based on CDC surveillance data (2016- 2019)c
•Initial efficacy & waning
Sanofi: Constant first 5 months as in trials, linear decay from month 6 to month 10
UM-CDC: Sigmoid decay up to 10 months; average residual protection in first 5 months equals constant
efficacy from trials
a  McLaurin et al. J Perinatol. 2016;36(11):990- 996
b  CDC unpublished data from the New Vaccine Surveillance Network (NVSN) (December 2016 to September 2020)
c  Bowser et al., J Infect Dis. 2022 Aug 15; 226(Suppl 2): S225– S235
d Rainisch et al. Vaccine . 2020;38(2):251- 257
59UM-CDC Sanofi
Risk of RSV hospitalization (Infants <12
months of age)1.30%
(0.60% - 3.11%)a1.42%
(0.49% - 4.37%)b
Medical costs per RSV hospitalization$11,487
($11,042 - $11,993)c$18,790 – $28,812
(age -and term dependent)d
Medical costs per RSV outpatient visit$82
($46 - $118)c$153
(no variation reported)
a Data from CDC-funded New Vaccine Surveillance Network (NVSN) (December 2016 to September 2020) (range values are the lowest and highest within the first 11 months of age)
b Weighted average term - specific populations shares (range values are the lowest and highest within the first 11 months of age)
c Adapted from Bowser et al., J I nfect Dis . 2022 Aug 15; 226(Suppl 2): S225– S235 (A systematic review study funded by Sanofi)
d Costs in the base - case varied by age, term at birth and by whether Intensive Care Unit or Mechanical Ventilator were needed while hospitalized using percentages as wights;  data reported
in McLaurin (2016)Sanofi and UM-CDC models comparison:
Differences in key inputs
Sanofi and UM-CDC models comparison:
Base -case risk of RSV -related hospitalization by age
600.00%0.50%1.00%1.50%2.00%2.50%3.00%3.50%4.00%4.50%5.00%
0 months 1 months 2 months 3 months 4 months 5 months 6 months 7 months 8 months 9 months 10 months 11 monthsRisk of Hospitalization
Age in monthsUM-CDC SanofiUM-CDC model: Laboratory -
confirmed RSV -associated
hospitalization rates from New
Vaccine Surveillance Network (NVSN) data for children under 2 years of age (December 2016 to September 2020)
Sanofi model : Age and term-
specific weighted average of
hospitalization rates in infants using reported rates in McLaurin
(2016)
0%5%10%15%20%25%30%35%Percent of annual cases
Month of seasonUM-CDC
Sanofi
61Sanofi intervention
UM-CDC interventionSanofi and UM-CDC models comparison:
RSV-season and intervention*
Sanofi
InterventionUM- CDC
Intervention
WiS (Within RSV
season). All Infants
born in- season
(i.e., October 1stto
Feb 29th)At birth, if born
October 1st
to
March 31st
WiS: All infants 0 -3
months of age at the
start of RSV season
(i.e., in October)In October, if born in
April
June
August
OoS (Out of RSV
season): All infants
born OoS at the start
of the RSV season
(i.e., in October) In November, if born
in
May
July
September
* RSV -season and Intervention period in UM- CDC model are based on NREVVS seasonality (2016 -2019).
Intervention period in Sanofi model ends in February ( a month short from end of MA RSV season, Rainisch et al., Vaccine . 2020;38(2):251- 257. Technical appendix)
Sanofi and UM-CDC:  Initial nirsevimab efficacy
and uptake
62a MELODY trial and Phase 2b recommended dose
b Assumed non- in feriority with palivizumab,  Hammitt et al.,  N Engl J Med. 2022;386(9):837- 846UM-CDC Sanofi
Initial efficacy against MA RSV LRTI:
Inpatient and outpatient (%)a80.0
(68.5 –86.1)a79.0
(68.5 –86.1)a, b
0%20%40%60%80%100%
0 2 4 6 8 10 12Efficacy
Months after immunizationSanofi and UM-CDC: Assumption on duration
of nirsevimab
63SanofiInitial efficacy against MA LRTI = A constant
protection over 5 months, Then, a linear decay of efficacy from month 6 to month 10
No residual protection after 10 months
UM-CDCInitial efficacy against LRTI = Average 5 months
efficacy equals to trial estimatesSigmoid decay up to 10 months and then 0% afterwards;
Calibrated such that the first 5 months efficacy
equals trial estimates

UM-CDC model: comparison of base case &
selected scenarios
64a    Base -c ase nirsevimab cost $300 per dose, immunization is for only the 1st  season
b
  LRTI=Lower respiratory tract infection,  URTI= Upper respiratory tract infection
c    Cost per QALY saved estimated by varying nirsevimab cost per dose from $200 (low) to $500 (high), immunization is for on ly th e
1stseason Scenario UM-CDC
Nirsevimab cost per $500/dose (1stseason )c$244,677
Intervention period October to February $107,963
Base case a(Nirsevimab cost $300/dose, 1stseason) $102,805
Prevention of All MA RSV visits (LRTI and URTI)b$45,092
Nirsevimab cost per $200/dose (1stseason )c$31,869
Limitations
65•Factors not considered that may result in overestimating the ICER
(underestimating the cost- effectiveness) of nirsevimab immunization
•In base -case: both models assumed
•No protection against URTI
•No protection against asymptomatic/unattended LRTI
•Neither model included RSV- related costs incurred after discharge from an
RSV-associated hospitalization or emergency department visit:
•Productivity losses incurred by caregivers after discharge
•Both models assumed no indirect effects of nirsevimab immunization (i.e., no protection against RSV transmission)
Conclusion
66•Differences in key inputs among Sanofi and UM-CDC models explain differences in results:
•Nirsevimab cost per dose
•Seasonality and intervention period
•Duration of nirservimab efficacy
•Hospitalization rates
•Medical costs
•Base-case in both models:
•Nirsevimab would significantly reduce RSV disease burden in infants
•Data from clinical trials support impact estimates on disease reduction
•Economic value of using nirsevimab in infants could be cost-effective orcostly
•Reasonable nirsevimab price and duration of protection combined with careful design of
seasonal interventions would determine the cost-effectiveness value of routine
prophylaxis among infants ≤7 months of age entering their first RSV season, and those born during the RSV season
Acknowledgements
From NCIRD/CDC
•Jamison Pike
•Jefferson Jones
•Meredith McMorrow
•Mila M. Prill
•Katherine E. Fleming -D utra
•Michael Melgar
Al
so:
•Maternal/Pediatric RSV working group members
67

End of Summary

Summary: Economics of Preventing Respiratory Syncytial  Virus Lower Respiratory Tract Infections (RSV- LRTI) among US Infants with Nirsevimab  A SUMMARY REPORT COMPARING MODELS FROM: Sanofi AND University of Michigan and CDC Ismael R. Ortega -Sanchez, PhD NCIRD/CDC ACIP Meeting, February 23, 2023  46Disclaimer : The findings and conclusions in this report are those of the authors and do not necessarily represent the views of  the Centers for Disease Control and Prevention.  National Center for…


RSV Pediatric 04 Jones 508

Centers for Disease Control and Prevention
Evidence to Recommendations Framework:
Nirsevimab
Jefferson Jones MD MPH FAAP , CDR USPHS
ACIP General MeetingFebruary 23, 2023
Evidence to Recommendations Framework
71Nirsevimab is a form of passive immunization
Active immunity results from infection or vaccination, which triggers
animmune response
Passive immunity is when a person receives antibodies from an external source
–From mother to baby through transplacental or breastmilk transfer
–Direct administration of antibodies, such as IVIG or monoclonal antibodies
https://www.cdc.gov/vaccines/vac -gen/immunity -types.htm
72Evidence to Recommendations (EtR ) Framework
Policy Questions
Should one dose of nirsevimab be recommended a) at birth for all
infants born during October to March and b) when entering first RSV
season and <8 months of age for all infants born during April through
September?
Should one dose of nirsevimab be recommended for children <20 months of age with increased risk of severe disease entering their
second RSV season?
73Evidence to Recommendations (EtR ) Framework
PICO Question 1
Population All infants born during Apr -Sept who are <8 months of age when
entering their first RSV season and infants born during Oct- Mar
Intervention Nirsevimab (1 injection prior to start of RSV season or at birth if born
during season, 50 mg if <5 kg or 100 mg if ≥5 kg)
Comparison No nirsevimab prophylaxis
Outcomes Medically -attended RSV- associated lower respiratory tract
infection (MA -LRTI)
RSV-associated LRTI with hospitalization
RSV-associated LRTI with ICU admission
RSV-associated death
All-cause MA -LRTI
All-cause LRTI- associated hospitalization
Serious adverse events
74Evidence to Recommendations (EtR ) Framework
EtRDomain 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?
EtRDomain: Public Health Problem
Is RSV -associated disease among infants <8 months of age entering their
first RSV season and infants born during the RSV season of public health
importance?
76Changes in seasonality of RSV transmission following
SARS -CoV2 introduction —NREVSS1, 2016 –2023
2016- 17
1017- 18
2018- 19
2019- 20
2020- 21
2021- 22
2022- 23
1Displayed results are among ~200 commercial, hospital, and
state/local public health laboratories which consistently report RSV
PCR tests at an annual average of ≥10 PCR tests and ≥30 weeks of the
12-month surveillance year. Testing is clinician -directed and results
include all ages.
77Each year among U.S. children aged less than 5 years,
RSV is associated with…
~1,500,0003
outpatient visits~520,0003
emergency department visits58,000 -80,0003,4,5
hospitalizations100-3001,2
deaths
1Thompson et al, JAMA, 2003; 2Hansen et al, JAMA Network Open, 2022; 3Hall et al, NEJM, 2009; 4Rha et al., Peds, 2020; 5McLaughlin et al, J
Infect Dis, 2022; (*estimate 80,000 hospitalizations in infants <1y)
78Epidemiology of RSV
Pre-pandemic RSV seasonality is well defined with limited geographic
variability in most of the U.S.
RSV is the most common cause of hospitalization in U.S. infants
–Highest hospitalization rates in first months of life
–Risk declines by month with increasing age in infancy and early childhood
Prematurity and other chronic diseases increase risk of RSV -associated
hospitalization, but most hospitalizations are in healthy, term infants
79Public Health Problem- Work Group Interpretation
Is RSV -associated disease among infants <8 months of age entering
their first RSV season and infants born during the RSV season of
public health importance?
NoProbably
NoProbably
YesYes VariesDon’t
know
EtRDomain: Benefits and Harms
Do the desirable effects outweigh the undesirable effects?
81Outcomes, importance, and data sources
Outcome ImportanceaData sources
Benefits
Medically attended RSV LRTI Critical Phase 3 and phase 2b RCTb
RSV LRTI with hospitalization Critical Phase 3 and phase 2b RCTb
RSV LRTI with ICU admission Critical Phase 3 and phase 2b RCTb
Death due to RSV respiratory illness Critical No RSV deaths in trials
All-cause medically attended -LRTI Important Phase 3 and phase 2b RCTb
All-cause LRTI -associated hospitalization Important Phase 3 and phase 2b RCTb
HarmsSerious Adverse Events (SAEs) Important Phase 3 and phase 2b RCT
b
a Three options: Critical; Important but not critical; Not important for decision making
bIncludes 3012 participants in the phase 3 trials (born >34 weeks gestational age [GA]) and 860 participants in phase 2b trial (born 29- 34 weeks GA). Among phase 2b trial
participants, only those who received the recommended dose were included: infants ≥5 kg received a dose (50mg) that was deter mined to be too low to be efficacious for this
weightLRTI: Lower respiratory tract infection, RCT: randomized control trial, ICU: intensive care unit
82Efficacy estimates and concerns in certainty of
assessment
Outcome Efficacy estimate* Concerns in certainty of assessment
Benefits
Medically attended RSV LRTI 79.0% (95% CI: 68.5% –86.1%) Not serious (indirectness)
RSV LRTI with hospitalization 80.6% (95% CI: 62.3% –90.1%) Not serious (indirectness)
RSV LRTI with ICU admission 90.0% (95% CI: 16.4% –98.8%) Serious (imprecision): Too few events
Not serious (indirectness)
Death due to RSV respiratory
illnessNone recorded N/A
All-cause medically attended -
LRTI34.8% (95% CI: 23.0– 44.7%) Not serious (indirectness)
All-cause LRTI -associated
hospitalization44.9% (95% CI: 24.9% –59.6%) Not serious (indirectness)
*Pooled phase 2b (excluding underdosed) and phase 3 trial estimate comparing nirsevimab arm to placebo arm
83Efficacy estimates and concerns in certainty of
assessment
Outcome Efficacy estimate* Concerns in certainty of assessment
Benefits
Medically attended RSV LRTI 79.0% (95% CI: 68.5% –86.1%) Not serious (indirectness)
RSV LRTI with hospitalization 80.6% (95% CI: 62.3% –90.1%) Not serious (indirectness)
RSV LRTI with ICU admission 90.0% (95% CI: 16.4% –98.8%) Serious (imprecision): Too few events
Not serious (indirectness)
Death due to RSV respiratory
illnessNone recorded N/A
All-cause medically attended -
LRTI34.8% (95% CI: 23.0– 44.7%) Not serious (indirectness)
All-cause LRTI -associated
hospitalization44.9% (95% CI: 24.9% –59.6%) Not serious (indirectness)
*Pooled phase 2b (excluding underdosed) and phase 3 trial estimate comparing nirsevimab arm to placebo arm
84Efficacy estimates and concerns in certainty of
assessment
Outcome Efficacy estimate* Concerns in certainty of assessment
Benefits
Medically attended RSV LRTI 79.0% (95% CI: 68.5% –86.1%) Not serious (indirectness)
RSV LRTI with hospitalization 80.6% (95% CI: 62.3% –90.1%) Not serious (indirectness)
RSV LRTI with ICU admission 90.0% (95% CI: 16.4% –98.8%) Serious (imprecision): Too few events
Not serious (indirectness)
Death due to RSV respiratory
illnessNone recorded N/A
All-cause medically attended -
LRTI34.8% (95% CI: 23.0– 44.7%) Not serious (indirectness)
All-cause LRTI -associated
hospitalization44.9% (95% CI: 24.9% –59.6%) Not serious (indirectness)
*Pooled phase 2b (excluding underdosed) and phase 3 trial estimate comparing nirsevimab arm to placebo arm
85Relative risk of SAEs and concerns in certainty of
assessment
Outcome Relative risk1Concerns in certainty of assessment
Harms
Serious Adverse Events
(SAEs)20.73 (95% CI: 0.59– 0.89) Serious (imprecision)
1Pooled phase 2b and phase 3 estimate comparing nirsevimab arm to placebo arm
2Adverse event resulting in death, hospitalization, significant disability, or requiring medical intervention.
Adverse events include respiratory symptoms.
86Summary of GRADE for nirsevimab
Outcome Importance Design
(# of studies)Findings Level of certainty
Benefits
Medically attended RSV
LRTICritical RCT (2)Nirsevimab is effective in preventing medically attended
RSV LRTIHigh
RSV LRTI with
hospitalizationCritical RCT (2)Nirsevimab is effective in preventing medically attended
RSV LRTI with hospitalizationHigh
RSV LRTI with ICU
admissionCritical RCT (2)Nirsevimab is likely effective in preventing medically
attended RSV LRTI with ICU admissionModerate
Death due to RSV Critical RCT (2) No deaths reported -
All-cause medically
attended -LRTIImportant RCT (2)Nirsevimab is effective in preventing all cause medically
attended LRTIHigh
All-cause LRTI -associated
hospitalizationImportant RCT (2)Nirsevimab is effective in preventing all cause hospitalization with respiratory diseaseHigh
Harms
Serious adverse events Critical RCT (1)SAEs were likely not more common in intervention group
than placebo groupModerate
11: High certainty; 2: Moderate certainty. 3: Low certainty; 4: Very low certainty.
87Summary of GRADE for nirsevimab
Outcome Importance Design
(# of studies)Findings Level of certainty
Benefits
Medically attended RSV
LRTICritical RCT (2)Nirsevimab is effective in preventing medically attended
RSV LRTIHigh
RSV LRTI with
hospitalizationCritical RCT (2)Nirsevimab is effective in preventing medically attended
RSV LRTI with hospitalizationHigh
RSV LRTI with ICU
admissionCritical RCT (2)Nirsevimab is likely effective in preventing medically
attended RSV LRTI with ICU admissionModerate
Death due to RSV Critical RCT (2) No deaths reported -
All-cause medically
attended -LRTIImportant RCT (2)Nirsevimab is effective in preventing all cause medically
attended LRTIHigh
All-cause LRTI -associated
hospitalizationImportant RCT (2)Nirsevimab is effective in preventing all cause hospitalization with respiratory diseaseHigh
Harms
Serious adverse events Critical RCT (1)SAEs were likely not more common in intervention group
than placebo groupModerate
11: High certainty; 2: Moderate certainty. 3: Low certainty; 4: Very low certainty.
88Summary of GRADE for nirsevimab
Outcome Importance Design
(# of studies)Findings Level of certainty
Benefits
Medically attended RSV
LRTICritical RCT (2)Nirsevimab is effective in preventing medically attended
RSV LRTIHigh
RSV LRTI with
hospitalizationCritical RCT (2)Nirsevimab is effective in preventing medically attended
RSV LRTI with hospitalizationHigh
RSV LRTI with ICU
admissionCritical RCT (2)Nirsevimab is likely effective in preventing medically
attended RSV LRTI with ICU admissionModerate
Death due to RSV Critical RCT (2) No deaths reported -
All-cause medically
attended -LRTIImportant RCT (2)Nirsevimab is effective in preventing all cause medically
attended LRTIHigh
All-cause LRTI -associated
hospitalizationImportant RCT (2)Nirsevimab is effective in preventing all cause hospitalization with respiratory diseaseHigh
Harms
Serious adverse events Critical RCT (1)SAEs were likely not more common in intervention group
than placebo groupModerate
11: High certainty; 2: Moderate certainty. 3: Low certainty; 4: Very low certainty.
89Overall evidence rating
Overall evidence rating: moderate certainty
Downgraded based on imprecision for protection against ICU admissions
because of few recorded events and imprecision of SAEs because rare
events are unlikely to be detected
90Benefits and Harms
How substantial are the desirable anticipated effects?
–How substantial are the anticipated effect for each main outcome
for which there is a desirable effect?
Minimal Small Moderate Large Varies Don’t know
91Benefits and Harms
How substantial are the undesirable anticipated effects?
–How substantial are the anticipated effect for each main outcome
for which there is an undesirable effect?
Minimal Small Moderate Large Varies Don’t know
92Benefits and Harms
Do the desirable effects outweigh the undesirable effects?
–What is the balance between the desirable effects relative to the
undesirable effects?
Favors intervention ( Nirsevimab )
Favors comparison (No intervention)
Favors both
Favors neither
Unclear
EtRDomain: Values
Criterion 1: Does the target population feel that the desirable effects are
large relative to undesirable effects?
Criterion 2: Is there important uncertainty about, or variability in, how
much people value the main outcomes?
94About one-third (33%) of respondents thought their baby ‘definitely’ or
‘probably’ would get an RSV infection within one year after being born*
Definitely or
probably would g e t  RSV
Unsure
Definitely or probably would not
g e t  RSV
*CDC and University of Iowa/RAND survey, unpublished, of 523 people who were actively pregnant or pregnant within last
12 months; conducted during 12/2022–1/2023; 68% of respondents had previously heard of RSV.
95
70% of respondents said they ‘definitely’ or ‘probably’ would get an
RSV antibody injection for their baby if safe and effective*
‘Definitely’ or
‘ Probably’  would get antibody
Unsure
‘Definitely’  or ‘ Probably’  would not
get antibody
*If antibody injection was approved by FDA and recommended by CDC. CDC and University of Iowa/RAND survey, unpublished
9663% of respondents said they were more worried or equally worried
about their baby experiencing side effects from an RSV antibody
injection vs. symptoms if sick with RSV
Worried about
bad side effects from antibodies
W orried about both
W orried about bad disease symptoms
CDC and University of Iowa/RAND survey, unpublished
97Parent attitudes about RSV
38% of respondents believe that their baby would have no symptoms or
mild symptoms if they got sick with RSV
24% expressed uncertainty about the disease severity or treatability if their
baby got sick with RSV
Despite being unsure or perceiving RSV risk to be low, respondents were
worried their baby would need to be hospitalized if they got sick with RSV
(mean response 4 of 5 with 5 being most worried)
CDC and University of Iowa/RAND survey, unpublished
98Values
Criterion 1: Does the target population feel that the desirable effects
are large relative to undesirable effects?
NoProbably
NoProbably
YesYes VariesDon’t
know
99Values
Criterion 2: Is there important uncertainty about, or variability in, how
much people value the main outcomes?
Important uncertainty or variability
Probably important uncertainty or variability
Probably not important uncertainty or
variability
No important uncertainty or variability
No known undesirable outcomes
EtRDomain: Acceptability
Is immunization with nirsevimab acceptable to key stakeholders?
101Provider survey
In survey by Alliance for Patient Access and National Coalition for Infant
Health of 175 providers using YouGov to poll U.S. physicians
–99% agree that parents need more information about RSV
–86% report including RSV education as part of routine care
–97% said immunizations could help prevent RSV
–92% agreed that RSV immunization policy should ensure all children
get access
https://admin.allianceforpatientaccess.org/wp -content/uploads/2023/01/AfPA -and-NCfIH_The -Indirect -Impact -of-RSV_Survey -Report_Ja n-2023.pdf
102Importance of RSV prevention recognized by relevant
national organizations
AAP states that development of safe and effective RSV immunization is a
priority
National Foundation for Infectious Disease roundtable agreed on the
importance of rapid adoption and deployment of evidence -based RSV
prevention
–Included National Association of County and City Health Officials
AAP COID BGC Pediatrics 2014 Aug;134(2):415 -20.
https://www.nfid.org/wp -content/uploads/2022/04/NFID -RSV-Call-to-Action.pdf
103Acceptability
Is immunization with nirsevimab acceptable to key stakeholders?
NoProbably
NoProbably
YesYes Varies Don’t know
EtRDomain: Feasibility
Is nirsevimab feasible to implement among all infants <8 months of age
entering their first RSV season and infants born during the RSV season?
105Administration and storage
Administered as intramuscular injection using pre -filled, single -use syringe
available in the following doses for infants born during or entering 1st RSV
season:
–50mg (0.5mL) for infants weighing <5 kg or
–100mg (1.0 mL) for infants ≥5 kg
For high -risk infants and children entering 2ndRSV season, dosing is 200mg
(two 100 mg doses administered at the same time
One dose of nirsevimab per season
Storage at refrigerator temperatures (2 °C -8°C)
May be kept at room temperature (20 °C -25°C) when protected from light
for a maximum of 8 hours
Beyfortus summary of product characteristics. European Medicines Agency  https://www.ema.europa.eu/en/documents/product -information/beyfortus -epar-product -information_en.pdf
106ACIP considerations
Nirsevimab would be first passive immunization product to be
independently included in CDC immunization schedule
Proposed indication is for all infants and would result in population -level
impacts
Nirsevimab inclusion in Vaccines For Children (VFC) program undetermined
107Considerations related to nirsevimab being classified
as a drug
Certain types of health care workers (e.g., medical assistants) can
administer vaccines but might not be able to administer a monoclonal
antibody depending on jurisdiction
Adverse events would be reported to FDA Adverse Event Reporting
System rather than the Vaccine Adverse Event Reporting System
Billing and administration codes for nirsevimab have not been finalized
Some state immunization information systems might not be able to include products that are considered drugs and not vaccines
108Feasibility
Is immunization with nirsevimab feasible to implement among all
infants <8 months of age entering their first RSV season and infants
born during the RSV season?
No Probably
NoProbably
YesYes Varies Don’t know
EtRDomain: Resource Use
Is nirsevimab immunization among all infants <8 months of age entering
their first RSV season and infants born during the RSV season a
reasonable and efficient allocation of resources?
110Cost -effectiveness results
Cost of nirsevimab per infant1 ICER ($/QALY)2
$300 $ 102,805
$500 $ 244,677
ICER: Incremental cost effectiveness ratio, QALY: quality -adjusted life year
1 Cost includes cost of administration.
2 Restricted to lower respiratory tract infection (i.e., upper respiratory infections from RSV excluded). Incorporated costs of
outpatient, ED, inpatient, and death from RSV LRTI. Incidence of RSV -associated outpatient, ED, and inpatient events based on
published and unpublished NVSN estimates. Nirsevimab efficacy based on phase 2b and phase 3 trial results. Other model
assumptions from published literature. Cost of palivizumab not incorporated.
111Resource Use
Is nirsevimab immunuization among a ll infants <8 months of age
entering their first RSV season and infants born during the RSV season a
reasonable and efficient allocation of resources?
At $300 per infant
At $500 per infantNo Probably
NoProbably
YesYes Varies Don’t know
No Probably
NoProbably
YesYes Varies Don’t know
EtRDomain: Equity
What would be the impact of nirsevimab on health equity?
113Equity and payment
Nirsevimab inclusion in Vaccines For Children (VFC) program undetermined
If not included in VFC, state Medicaid, Medicaid expansion (Children’s
Health Insurance Programs), and private insurance would likely cover
nirsevimab
–Underinsured and uninsured would likely have reduced access
114Seasonal incidence per 1,000 children of RSV -associated hospitalizations
among American Indian and Alaska Native children <5 years of age, Nov
2019 -May 2020 ( SuNA )*
*Hartman et al,  R SV 2022 12thInternational Symposium,  B elfast 9/29/2022- 10/2/2022; A twell et al.  (manuscript submitted,  under peer -review) SuNA = RSV Surveillance
among Native A merican Persons
**In cid e n ce  o f RSV -associated hosp italization in 2019 -2020 from Curns et al. (unp ub lished manuscrip t in p rep aration) included fo r comp arison. NVSN = New V accine
Surveillance Network.Age  Chinle, Arizona   Whiteriver,
Arizona  Anchorage, Alaska  Yukon -Kuskokwim
Delta, Alaska  NVSN** for
comparison
0-5 Months  83.0 (52.0, 132.5)  70.4 (36.3, 136.6)  35.7 (20.4, 62.6)  132.3 (98.2, 178.1)  21.6 (20.0 , 23.3)
6-11 Months  61.6 (35.9, 105.8)  90.1 (50.0, 162.3)  0.0 (0.0, 10.8)  91.6 (64.0, 131.0)  8.2 (7.1 , 9.3)
0-11 Months  71.8 (50.4, 102.4)  80.6 (51.9, 125.2)  19.2 (11.2, 33.0)  112.2 (89.3, 141.0)  14.9 (13.9 , 16.0)
12-23 Months  42.1 (27.2, 65.3)  38.7 (22.0, 68.1)  15.6 (8.7, 27.7)  26.4 (16.6, 41.8)  4.5 (3.9 , 5.2)
24-59 Months  10.9 (6.8, 17.4)  8.2 (4.2, 16.0)  1.1 (0.3, 3.8)  5.9 (3.2, 10.9)  1.2 (1.2 , 1.5)
0-59 Months  27.2 (21.4, 34.4)  25.4 (18.7, 34.5)  7.7 (5.3, 11.1)  32.7 (26.9, 39.7)  4.6 (4.3, 4.8)

115RSV rates of severe disease by race and ethnicity
National studies of death certificates found higher rates among non -
Hispanic black compared with non -Hispanic White children1
Hospitalization rates using New Vaccine Surveillance Network (NVSN) data
have shown mixed results2
–Several studies have shown no differences by race or ethnicity3-5
–Even when significant, relative risk for non -Hispanic Black and Hispanic
children mildly increased (e.g., relative risk of 1.2 -2.2)5-6
1. Hansen J Infect Dis 2022 Aug 15;226(Suppl 2):S255 -S266
2. NVSN analyses compared incidence rates of non -Hispanic Black, non -Hispanic White,
and Hispanic children
3. Hall Pediatrics 2013 Aug;132(2):e341 -84. Hall NEJM 2009;360(6):588 –598
5. Iwane Pediatrics 2004 Jun;113(6):1758 -64, findings differed by age group
6. Rha Pediatrics 2020 Jul;146(1):e20193611, findings differed by age group
116Equity
What would be the impact of nirsevimab on health equity?
Reduced
Probably reduced
Probably no impact
Probably increased
Increased
Varies
Don’t know
117EtRSummary: All infants 1st RSV season
EtRDomain Question(s) Work Group Judgments
Public Health
ProblemIs RSV -associated disease among infants <8 months of age
entering their first RSV season and infants born during the
RSV season of public health importance?Ye s
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?Moderate to large
Minimal to small
Ye s
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?Y es/probabl y yes
No consensus
Acceptability Is nirsevimab acceptable to key stakeholders? Y es/probabl y yes
Feasibility Is the intervention feasible to implement? Probabl y yes
Resource Use Is the intervention a reasonable and efficient allocation of resources? Y es/probabl y yes
(depends on price)
Equity What would be in the impact of the intervention on health equity?—
118Evidence to Recommendations Framework
Summary: Work Group Interpretations
All infants 1st RSV season
Balance of
consequencesUndesirable
consequences
clearly
outweigh
desirable
consequences
in most settingsUndesirable
consequences
probably
outweigh
desirable
consequences
in most settingsThe balance
between
desirable
and undesirable
consequences
isclosely
balanced or
uncertainDesirable
consequences
probably
outweigh
undesirable
consequences
in most settingsDesirable
consequences
clearly
outweigh
undesirable
consequences
in most settingsThere
isinsufficient
evidence
todetermine
thebalance of
consequences
119Evidence to Recommendations Framework
Summary: Work Group Interpretations
All infants 1st RSV season
Type of
recommendationWe do not
recommend the
interventionWe recommend
theintervention for
individuals based on
shared
clinical decision -
makingWe recommend
theintervention
2ndindication
Should one dose of nirsevimab be recommended for children <20 months
of age with increased risk of severe disease entering their second RSV
season?
121Evidence to Recommendations (EtR ) Framework
PICO Question
Population Children age <20 months who are at increased risk of severe disease
with RSV and who are entering their second RSV season
Intervention Nirsevimab (200 mg [2 x 100 mg] injection prior to start of second
RSV season)
Comparison No nirsevimab prophylaxis
Outcomes Medically attended RSV associated lower respiratory tract
infection (LRTI)
Medically attended RSV associated LRTI with hospitalization
Medically attended RSV associated LRTI with ICU admission
RSV-associated death
All-cause MA LRTI
All-cause LRTI associated hospitalization
Serious adverse events
EtRDomain: Public Health Problem
Is RSV disease among children who are at high risk of severe disease in
their 2nd RSV season of public health importance?
RSV-associated hospitalization rates in children aged <5 years,
New Vaccine Surveillance Network, 2016 -2020
0-5 months 6-11 months 12-23 months 24-59 months 0-59 months
2016-2020 18.5 7.5 3.9 1.0 3.9.05.010.015.020.025.0Hospitalization Rate per 1000
124Relative risk in 1st RSV season compared with 2nd RSV
season
CDC, unpublished dataFigure:  RSV hospitalization rate ratios by age in months among children <2 years old, New Vaccine
Surveillance Network, December 2016 through September 2020.
6.1
3.4
1.9
012345678
0-2 vs. 12-23 3-5 vs. 12-23 6-11 vs. 12-23Rate Ratio
Comparison (age in months)
125High- risk second season indications proposed by
manufacturer
Children up to 24 months of age who remain vulnerable to severe RSV
disease through their second RSV season, which may include but is not
limited to children with:
– Chronic lung disease of prematurity (CLD)
– Hemodynamically significant congenital heart disease (CHD)
– Immunocompromised states
– Down syndrome
– Cystic fibrosis
– Neuromuscular disease
– Congenital airway anomalies
In MEDLEY study, palivizumab -eligible children with hemodynamically -
significant CHD and CLD were included
126Chronic conditions recommended by American Academy of Pediatrics
(AAP) to qualify for palivizumab when entering 2ndRSV season
Group recommended for palivizumab
–CLD of prematurity if require medical support (chronic corticosteroid
therapy, diuretic therapy, or supplemental oxygen) during the 6 -month
period before the start of the second RSV season
Groups that can be considered for palivizumab
–Profoundly immunocompromised
–Cystic fibrosis if manifestations of severe lung disease (previous hospitalization for pulmonary exacerbation in the first year of life or
abnormalities on chest XR or CT that persist when stable) or weight for
length < 10th percentile.
American Academy of Pediatrics Committee on Infectious Diseases and Bronchiolitis Guidelines Committee. Updated guidance for palivizumab prophylaxis among
infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics. 2014 A ug;134(2):415 -20.
127WG considerations for conditions and populations to
be considered “high risk”
Same children eligible for palivizumab when entering 2nd RSV season per American
Academy of Pediatrics recommendations
–Children with chronic lung disease of prematurity if require medical support (chronic corticosteroid therapy, diuretic therapy, or supplemental oxygen) during the 6- month period before the start of the second RSV season
–Children who are profoundly immunocompromised
–Children with cystic fibrosis with manifestations of severe lung disease
(previous hospitalization for pulmonary exacerbation in the first year of life or abnormalities on chest XR or CT that persist when stable) or weight for length < 10th percentile
Other conditions are under review
American Academy of Pediatrics Committee on Infectious Diseases and Bronchiolitis Guidelines Committee. Updated guidance for palivizumab prophylaxis among
infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics. 2014 A ug;134(2):415 -20.
128Public Health Problem- Work Group Interpretation
Is RSV disease among children who are at high risk of severe disease
in their 2nd RSV season of public health importance?
NoProbably
NoProbably
YesYes VariesDon’t
know
EtRDomain: Benefits and Harms
Do the desirable effects outweigh the undesirable effects?
130MEDLEY study: Dose for children ≤24 months with
CLD/CHD entering their second RSV season
130
Domachowske e t  a l. https://www.nejm.org/doi/full/10.1056/NE JMc2112186 ,  https://clinicaltrials.gov/ct2/show/NCT03959488

131Outcomes, importance, and data sources
Outcome Importancea Data sources
Benefits
Medically attended RSV LRTI Critical MEDLEY , Domachowske et al.
RSV LRTI with hospitalization Critical No available data
RSV LRTI with ICU admission Critical No available data
Death due to RSV respiratory illness Critical No available data
All-cause medically attended -LRTI Important No available data
All-cause LRTI -associated hospitalization Important No available data
HarmsSerious Adverse Events (SAEs) Important MEDLEY , Domachowske et al.
a Three options: Critical; Important but not critical; Not important for decision making
132Medically attended (MA)* RSV LRTI
MEDLEY designed as safety and pharmacokinetics (PK) study
No clinical efficacy data available for children <24 months at high risk of
severe RSV disease entering their second RSV season
PK data from Phase 2b, Phase 3, and MEDLEY studies (i.e., among infants
<12 months of age) were analyzed using population modelling
Area under the curve (AUC0-∞) was derived using individual estimates as a
measure of exposure to nirsevimab
AUC0-∞was then correlated to efficacy for prevention of the first episode of
MA RSV LRTI in infants age <12 months from Phase 2b, Phase 3 and
MEDLEY trials
*Medically attended means presented for medical care, either outpatient or inpatient
133Pharmacokinetic data for children ≤24 months with
CLD/CHD entering their second RSV season who
received 200 mg of nirsevimab
Dashed black line is the AUC Exposure -Response
threshold (12.8 day*mg/mL)
Notes: black points are individual AUC predictions.
AUC = area under the serum concentration- time curve
derived from dose and post -hoc clearance values at
baseline from the final population PK model; CHD =
congenital heart disease; CL = clearance; CLD = chronic lung disease; GA = gestational age
Pre-determined threshold of
80% meeting PK criteria met
Data from Sanofi/AstraZeneca
134GRADE: medically attended RSV LRTI (n=1 study)
Measures of effect:
–Pharmacokinetic extrapolation from efficacy in infants <12 months of
age for prevention of the first MA RSV LRTI to pharmacokinetic levels in
children ≤24 months with CLD/CHD entering their second RSV season
Concerns in certainty assessment:
–Very serious (indirectness due to surrogate outcome, outcome
established in 1st season, and population that does not match proposed indication)
Evidence type:
–Low certainty
135Available safety data from children ≤24 months with
CLD/CHD entering their second RSV season who
received nirsevimab (200 mg) or palivizumab (15 mg/kg)
Subjects withCLD/CHD Cohort
Palivizumab/
Palivizumab1
(N=42)
N (%)Palivizumab / Nirsevimab
1
(N=40)N (%)Nirsevimab / Nirsevimab
1
(N=180)N (%)
At least one adverse event229 (69.0) 29 (72.5) 126 (70.0)
At least one serious event30 ( 0.0) 4 (10.0) 17 ( 9.4)
At least one investigational product -related
event0 ( 0.0) 0 ( 0.0) 0 ( 0.0)
Any adverse event with outcome of death 0 ( 0.0) 0 ( 0.0) 0 ( 0.0)
1Palivizumab / Palivizumab  = Palivizumab  in season 1 / Palivizumab  in season 2; Palivizumab  / Nirsevimab  = Palivizumab  in season 1 /Nirsevimab  in season 2;
Nirsevimab  / Nirsevimab = Nirsevimab  in season 1 / Nirsevimab  in season 2
2A ny untoward medical occurrence (e.g.,  unintended abnormal laboratory ,  symptom,  or disease temporally associated with product , whether or not considered
associated);3AE resulting in death, hosp italization, significant disab ility, or required medical intervention.
Data from Sanofi/A straZeneca
136GRADE: Serious adverse events (n=1 study)
Measures of effect
–Relative Risk: 8.4 (95% CI: 0.52 -135.50)1
–Absolute risk: 176 more cases per 1,000 immunized (95% CI: 11 fewer
to 1,000 more)
Concerns in certainty assessment
–Serious (indirectness because comparison group is palivizumab
recipients rather than placebo)
–Very serious (imprecision)
Evidence type:
–Very low certainty
1Relative risk of an serious adverse event among children who received nirsevimab in their 2nd RSV season compared with childr enwho received palivizumab their 2nd
RSV season. Because no SAEs were reported in palivizumab group, 0.5 was added to both the nirsevimab and the palivizumab groups t o calculate relative risk.
137Summary of GRADE for nirsevimab dose for second season
Outcome Importance Design
(# of studies)Findings Level of certainty
Benefits
Medically attended  (MA) RSV LRTICritical 3 Nirsevimab might be effective in preventing MA RSV LRTI Low
RSV LRTI with
hospitalizationCriticalNo available data
RSV LRTI with ICU
admissionCriticalNo available data
RSV-associated deathCriticalNo available data
All cause medically attended LRTI ImportantNo available data
All cause hospitalization with respiratory diseaseImportantNo available data
Harms
Serious adverse events
(SAEs)Critical 1SAEs might not be more common in intervention group
than placebo groupVery low137
138Overall evidence rating
Overall evidence rating: Very low certainty
Downgraded based on indirectness because pharmacokinetic data used as
surrogate for efficacy, population did not include children that matches
proposed indication, study small in size, and no placebo group was
included for comparison
139Benefits and harms of nirsevimab
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
140Benefits and harms of nirsevimab
How substantial are the undesirable anticipated effects?
–How substantial are the anticipated effect for each main outcome
for which there is an undesirable effect?
Minimal Small Moderate Large Varies Don’t know
141Benefits and harms of nirsevimab
Do the desirable effects outweigh the undesirable effects?
–What is the balance between the desirable effects relative to the
undesirable effects?
Favors intervention (Nirsevimab)
Favors comparison (No intervention)
Favors both
Favors neither
Unclear
EtRDomains: Values, Acceptability, and
Feasibility
143Values
Criterion 1: Does the target population feel that the desirable effects
are large relative to undesirable effects?
NoProbably
NoProbably
YesYes VariesDon’t
know
144Values
Criterion 2: Is there important uncertainty about, or variability in, how
much people value the main outcomes?
Important uncertainty or variability
Probably important uncertainty or variability
Probably not important uncertainty or
variability
No important uncertainty or variability
No known undesirable outcomes
145Acceptability
Is RSV prevention with nirsevimab acceptable to key stakeholders?
No Probably
NoProbably
YesYes Varies Don’t know
146Feasibility
Additional visit to provider might be needed for administration of
nirsevimab prior to beginning of 2nd RSV season
Is nirsevimab feasible to implement among high -risk children
<20 months of age entering their second RSV season?
No Probably
NoProbably
YesYes Varies Don’t know
EtRDomain: Resource Use
148Resource Use
Is nirsevimab use among a ll high-risk children aged < 20months of age
entering their second RSV season a reasonable and efficient allocation
of resources?
$600 per child
$1000 per childNo Probably
NoProbably
YesYes Varies Don’t know
No Probably
NoProbably
YesYes Varies Don’t know
EtRDomain: Equity
150Equity
Equity issues differ by chronic condition among infants and young children
Non -Hispanic Black populations experience higher rates of preterm birth
than non -Hispanic White population1
For children with cystic fibrosis, the majority are from non -Hispanic white
populations2
Hispanic populations may have higher prevalence of Down syndrome than
non-Hispanic White populations3
Hispanic and non -Hispanic American Indian and Alaska Native populations
may have higher prevalence of neuromuscular disorders than non -Hispanic
White populations3
1.https: //www.cdc.gov/reproductivehealth/maternalinfanthealth/pretermbirth.htm
2.McGarry Pediatr Pulmonol 2021 Jun;56(6):1496- 1503
3.Mai B irth Defects R es 2019 Nov 1;111(18):1420- 1435
151Equity
What would be the impact of nirsevimab on health equity among high -
risk children entering their 2ndRSV season?
Reduced
Probably reduced
Probably no impact
Probably increased
Increased
Varies
Don’t know
152Summary: Children at high risk entering 2nd RSV season
EtRDomain Question(s) Work Group Judgments
Public Health
ProblemIs RSV disease among children <20 months who are at high risk of severe disease of public health importance? Yes
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?Moderate
Minimal
Favors nirsevimab
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?Probably yes
Probably no
Acceptability Is nirsevimab acceptable to key stakeholders? Probably yes
Feasibility Is the intervention feasible to implement? Probably yes
Resource Use Is the intervention a reasonable and efficient allocation of
resources?$600: Probably yes
$1000: Probably yes or probably no
Equity What would be in the impact of the intervention on health
equity?-
153Evidence to Recommendations Framework
Summary: Work Group Interpretations
Children at high risk entering 2nd RSV season
Balance of
consequencesUndesirable
consequences
clearly
outweigh
desirable
consequences
in most settingsUndesirable
consequences
probably
outweigh
desirable
consequences
in most settingsThe balance
between
desirable
and undesirable
consequences
isclosely
balanced or
uncertainDesirable
consequences
probably
outweigh
undesirable
consequences
in most settingsDesirable
consequences
clearly
outweigh
undesirable
consequences
in most settingsThere
isinsufficient
evidence
todetermine
thebalance of
consequences
154Evidence to Recommendations Framework
Summary: Work Group Interpretations
Children at high risk entering 2nd RSV season
Type of
recommendationWe do not
recommend the
interventionWe recommend
theintervention for
individuals based on
shared
clinical decision -
makingWe recommend
theintervention
Summary
1561st RSV season
The WG recommends nirsevimab a) at birth for all infants born during
October to March and b) when entering first RSV season and <8 months of age for all infants born during April through September?
Many expressed concerns about feasibility and equity, particularly because inclusion in VFC is unknown
Some WG expressed concern that at higher prices, nirsevimab may not be a reasonable and efficient allocation of resources
1572nd RSV season
WG would like more time to consider which infants and children would be
sufficiently high risk to warrant nirsevimab in their 2ndRSV season
–Limited efficacy and safety data
–Limited data to measure the risk of severe disease in the 2ndRSV
season
–At this time, WG recommended nirsevimab for those who are eligible for palivizumab in their 2nd RSV season, since assumed to be cost effective
–WG will continue to evaluate other conditions
158ACIP Policy Questions
Should one dose of nirsevimab be recommended a) at birth for all infants
born during October to March and b) when entering first RSV season and
<8 months of age for all infants born during April through September?
Should one dose of nirsevimab be recommended for children <20 months
of age entering their second RSV season who are eligible for palivizumab in
their second RSV season?
159Acknowledgements
Meredith McMorrow
Lauren RoperKatherine Fleming -Dutra
Mila PrillAmanda Payne
Danielle Moulia
Morgan NajdowskiDavid Hutton
Jamie PikeIsmael Ortega- Sanchez
Andrew Leidner
Sara OliverMonica Godfrey
Evelyn Twentyman
Rebecca Morgan
Doug Campos -Outcalt
For more information, contact CDC
1-800- CDC-INFO (232- 4636)
TTY:  1 -888- 232-6348    www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Summary: Centers for Disease Control and Prevention Evidence to Recommendations Framework:  Nirsevimab Jefferson Jones MD MPH FAAP , CDR USPHS ACIP General MeetingFebruary 23, 2023 Evidence to Recommendations Framework 71Nirsevimab is a form of passive immunization Active immunity results from infection or vaccination, which triggers  animmune response Passive immunity is when a person receives antibodies from an external source –From mother to baby through transplacental or breastmilk transfer…