13 COVID Twentyman 508

Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation
use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.
Bridge Access Program
Ensuring no -cost, timely access to the 2023 -2024 COVID -19
vaccines for adults
Evelyn Twentyman, MD, MPH
Immunization Services Division
Centers for Disease Control and Prevention
Why Do We Need the Bridge Access Program for
COVID -19 Vaccines?
*Underinsured is defined here as related to vaccination coverage.
1. Data are internal CDC estimates.This program will serve as temporary bridge to the permanent and comprehensive Vaccines for
Adults Program proposed in the FY23 and FY24 President’s Budgets
24.8
7.1
23.0
51.0121.7Adult Population by Coverage Status (millions)1
Uninsured
Underinsured*
Medicaid Enrolled (19-64)
Medicare Enrolled
Privately Insured (19-64)
There are 25-30 million adults
(ages 18 -64) without
insurance , and additional
adults whose insurance will not
provide no -cost coverage for
COVID -19 vaccines after these
products are commercialized
Ensuring no -cost, timely access to COVID -19 vaccines
▪Established access for those with insurance
▪Established access for children
▪Ensuring no -cost access for adults
▪Program design to maximize proximity
▪Program design to maximize equity
▪Timely access for all
The analysis on which estimates of proximity are based considers a variety of provider types and locations that will
participate in the Bridge Access Program . Access may increase if additional providers participate.
•~8,000 317-enrolled providers
•~4,500 State -funded vaccine providers
•~1,400 HRSA -supported health centers (HRSA)
•~21k Pharmacies
•~10k CVS locations
•~9k Walgreens locations
•~2,000 eTrue North locations –number may
increaseProviders
Local Health Centers
Health Centers* will partner with
state immunization programs to
ensure access to COVID -19 vaccines
for uninsured adults
HRSA will provide funding to
participating HRSA -supported
health centers to support services
that will help ensure equitable
access. State immunization
programs will design distribution of
vaccines.Pharmacies
Pharmacies will ensure access to no -
cost COVID -19 vaccines using their
extensive footprints and community
partnerships
Vaccines will be donated by
manufacturers to pharmacies, and
administration costs will be
covered by CDC.Existing partnerships with state and
local health departments (S/LHDs)
will facilitate distribution of COVID -
19 vaccines through providers in
networks
CDC will manage purchase and
distribution of COVID -19 vaccines
and provide oversight and technical
assistance. State immunization
programs will design distribution of
vaccines.
Local Healthcare ProvidersWhere Will Vaccines Be Available Through the Bridge
Access Program?
*HRSA -funded health centers and Health Center Program look -alike organizations
Walgreens locations sourced from Walgreens Store Locator website early August 2023.
CVS locations sourced from CVS Store Locator website early August 2023.
eTN Pharmacy vaccination locations from ICATT/ eTN early September 2023.
HRSA Health Center COVID -19 Vaccine Program Participants (FQHCs) from HRSA early September 2023.
Providers who received shipment of 317-funded routine adult vaccine CY21 -23 from VTrckS late July 2023.
Providers who received shipment of State -funded routine adult vaccine CY21 -23 from VTrckS late July 2023.
Note: Some points may not be visible due to point
overlap. Points are displayed in order of site count from
least to most: top -eTN , HRSA, State, 317, Walgreens,
CVS -bottom)
Overall, 85% of uninsured
populations live <5 miles from
Bridge Access Program site :
•Urban: 97%
•Suburban: 59%
•Rural: 39%
Overall, 5% of uninsured
populations estimated to be
>10 miles from Bridge Access
Program siteNational Proposed Bridge Access Program Site Locations
Bridge Access Program Retail Pharmacy Approaches
▪▪CVS plans to administer doses within both their
storefronts and Minute clinics
▪▪Walgreens plans to administer doses in both their
storefronts and at off-siteevents targeting areas of low
access & low uptake
▪▪eTrueNorth is a pharmacy aggregator that
subcontracts with smaller pharmacies
–Intended to reach lower -access areas without other coverage
within the Bridge Access Program
–Additional subcontract negotiations between eTrueNorth and
possible additional participating pharmacies are ongoing

Ensuring no -cost, timely access to COVID -19 vaccines
▪Timely access for all
▪Established access for those with insurance
▪Established access for children
▪Ensuring no -cost access for adults
▪Program design to maximize proximity
▪Program design to maximize equity
The Bridge Program would address leading barriers to COVID -19 vaccination:Program design to maximize equity
•Lack of health insurance or a
regular provider
•Lack of proximity or
transportation to place of care•Inconsistent coverage across
health insurance policies
•Inconsistent outreach and
engagement from health
systems •History of
disparities ,discriminatory
patterns and racism
•Rise in inaccurate
inoformation about vaccinesAccessibility Availability Confidence
•Providing access to COVID -
19 vaccines for uninsured
and underinsured adults at
no cost•Designing for optimized
proximity (variety of
provider/site types, low -access
and low -coverage lists and
payments)•Supporting and growing
vaccine confidence through
partnerships with trusted and
welcome messengers
Lessons learned from 2022 -2023 COVID -19 bivalent booster uptake
Community -based partnerships are key
Community -based organizations and other partners work with CDC, pharmacies, jurisdictions, and HRSA -supported
health centers to reduce barriers to COVID -19 vaccine access and promote uptake. These partners are particularly critical to
reaching people who are uninsured or underinsured.
FUNDED PARTNERS
CBOs and other funded partners will:
• Host community outreach events to spread
awareness of the Bridge Program
• Work within their communities as trusted and
welcome messengers
• Partner with providers to hold vaccine clinics to
provide greater access to vaccination
• Develop educational materials to promote COVID -
19 vaccination and the Bridge Program
All
Americans

The Bridge Access Program is a temporary “bridge” to
a permanent Vaccines for Adults (VFA) Program
The Bridge Access Program serves as a temporary solution for access to COVID -19 vaccines for adults. VFA and
additional 317 funding are needed to bridge the gap in equitable access to immunization across the lifespan.

▪CDC’s Bridge Website
–A central location for information and communications assets
▪Program guides for specific implementing partners
▪Clinician -facing calls and materials for vaccine providers
▪Communications toolkit for partners
–Digital toolkit for program resources and promotional materials including key messages, sample newsletter, and
communications assets
▪vaccines.gov
–Where patients and care providers can go this week to find all sites providing no -cost COVID -19 vaccines through
the Bridge Access Program, as well as all other providers for COVID -19 or influenza vaccines
▪Bridge Access Program Call Center
–Available this week through 1 -800 -CDC -INFO
–https://www.cdc.gov/cdc -info/index.htmlResources for partners
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.
Thank you

Summary: Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Bridge Access Program  Ensuring no -cost, timely access to the 2023 -2024 COVID -19  vaccines for adults Evelyn Twentyman, MD, MPH Immunization Services Division Centers…


ACIP approach to mAbs

▪Passive immunization
–Transfer of preformed antibody produced externally to provide protection to the
recipient
–Provides temporary protection that wanes with time
–Transfer of maternal antibody across the placenta that provides protection in early
infancy is an example of passive immunization
▪Active immunization
–Administration of specific components of an infectious agent that elicit an immune
response in the recipient
–Immunology memory provides prolonged protection that may be lifelong
–Traditional vaccines provide active immunizationPassive and Active Immunization
▪With development of long -acting monoclonal
antibodies ( mAbs ), there is an opportunity to
provide protection beyond what can be
provided by traditional vaccines
▪Especially valuable when
–Full protection is needed without delay
–A traditional vaccine is not available
▪For some indications, a long -acting mAb
might provide “long enough” protection
–For a respiratory disease season
–For a critical part of a pregnancy
–For prevention of travel -related infectionMonoclonal antibodies for
prevention of infectious diseases
who -monoclonal -antibodies.jpg (2480 ×3508)

CDC will prioritize for ACIP consideration those long -acting monoclonal
antibodies for prevention of infectious diseases that are:
▪Expected to address conditions that result in a significant burden of
disease to the public’s health;
▪Not expected to present significant implementation issues –at least
from the perspective of mode of administration, storage and handling,
and frequency of administration --for immunization providers; and
▪Expected to be priced at a level allowing for incorporation into
immunization programs. CDC’s Approach to Prioritizing Long -Acting Monoclonal
Antibodies for Prevention of Infectious Diseases

Summary: ▪Passive immunization –Transfer of preformed antibody produced externally to provide protection to the  recipient –Provides temporary protection that wanes with time –Transfer of maternal antibody across the placenta that provides protection in early  infancy is an example of passive immunization ▪Active immunization –Administration of specific components of an infectious agent that elicit an immune  response in the recipient –Immunology memory provides prolonged protection that may be…


01 RSV 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
August 3, 2023

2Work group members (External)
ACIP Members
Sarah Long (chair)
Pablo Sanchez
Oliver Brooks
Camille KottonConsultants
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)GRADE/ EtRConsultants
Doug Campos -Outcalt
Rebecca MorganEx 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)
Lucia Lee (FDA -CBER)
Robin Wisch (FDA -CBER)
3Work group members (CDC)
Amber Winn
Chris Taylor
Tami Skoff
Angie Campbell
Michael Melgar
Amanda Payne
Nicole Dowling
Noelle Molinari
Claire Midgley
Fiona HaversPragna Patel
Andrea Sharma
Amadea Britton
Ruth Link -Gelles
Danielle Moulia
Megan Wallace
Monica Godfrey
Karen Broder
Naomi Tepper
Heidi MolineCDC ACIP Staff
Melinda Wharton
Stephanie Thomas
Jessica MacNeilHannah Rosenblum
Derrell Powers
Raigan Wheeler
Sally Ezra
Elizabeth Greene
Manisha Patel
Tom Shimabukuro
Demorah Hayes
Latifah BoyceCDC
Katherine Fleming -Dutra (co -lead)
Jefferson Jones (co -lead)
Meredith McMorrow
Mila Prill
Natalie Thornburg
Aron Hall
Ismael Ortega -Sanchez
Melissa Coughlin
Jamison Pike
Lauren RoperA. Patricia Wodi
Neil Murthy
Christine Olson
Anne Hause
Andrew Leidner
David Shay
Sarah Meyer
4▪Epidemiology and burden of RSV in infants
▪Virology and immunology of RSV
▪Safety and efficacy of nirsevimab
▪Cost effectiveness analysis for nirsevimab –CDC model
▪Cost effectiveness analysis for nirsevimab –Comparison with manufacturer model
▪Evidence to Recommendations framework for nirsevimab
▪Clinical considerations for nirsevimabPrevious maternal/pediatric RSV ACIP presentations on
nirsevimab
5Agenda: Thursday August 3, 2023
▪Evidence to Recommendations
Framework for nirsevimab
▪Nirsevimab implementation
considerations
▪Clinical considerations for nirsevimab
▪Workgroup considerations and proposed
recommendations and voting language
▪Vaccines for Children ResolutionDr. Jefferson Jones (CDC)
Dr. Georgina Peacock (CDC)
Dr. Jefferson Jones (CDC)
Dr. Jefferson Jones (CDC)
Dr. Jeanne Santoli (CDC)
6

7▪Infants aged <8 months born during or entering their first RSV season are
recommended to receive one dose of nirsevimab (50 mg for infants <5 kg and 100
mg for infants ≥5 kg)
▪Children aged 8–19 months who are at increased risk of severe RSV disease and
entering their second RSV season are recommended to receive one dose of
nirsevimab (200 mg) Proposed ACIP Voting Language

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,…


02 RSV jones 508

Centers for Disease Control and Prevention
Evidence to Recommendations Framework:
Nirsevimab Updates
Jefferson Jones MD MPH FAAP , CDR USPHS
Co-Lead, Respiratory Syncytial Virus Vaccines -Pediatric/Maternal Work Group
Coronavirus and Other Respiratory Viruses Division
National Center for Immunization and Respiratory Diseases
August 3, 2023
2Evidence to Recommendations ( EtR) Framework
Policy Questions
▪Should one dose of nirsevimab be recommended for infants aged <8 months born
during or entering their first RSV season (50 mg for infants <5 kg and 100 mg for
infants ≥5 kg)?
▪Should one dose of nirsevimab be recommended children aged 8 –19 months who
are at increased risk of severe RSV disease and entering their second RSV season
(200 mg)?
▪Given an average RSV season of 4 –5  months, infants aged 8 months and children
aged 20 months would be experiencing their second and third RSV seasons,
respectively
3Nirsevimab is a 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
IVIG= Intravenous Immunoglobulin Therapy
https://www.cdc.gov/vaccines/vac -gen/immunity -types.htm
4Evidence to Recommendations ( EtR) Framework
PICO Question 1
▪Population Infants aged <8 months born during or entering their first RSV
season
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 (LRTI)
▪RSV-associated LRTI with hospitalization
▪RSV-associated LRTI with ICU admission
▪RSV-associated death
▪All-cause medically attended LRTI
▪All-cause LRTI -associated hospitalization
▪Serious adverse events
5Evidence 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?
7Changes in seasonality of RSV transmission following
SARS -CoV2 introduction —NREVSS1, 2017 –2023
0510152025
27293133353739414345474951 135791113151719212325
Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun% PCR results RSV -positive
Epidemiologic week2017 –18 2018 –19 2019 –20 2020 –21 2021 –22 2022 –23
Abbreviation : PCR = polymerase chain reaction; RSV = respiratory syncytial virus. 1. https://www.cdc.gov/mmwr/volumes/72/wr/mm7214a1.htm
* 3-week centered moving averages of percentage of RSV -positive PCR results nationwide. The black dotted line represents the thr eshold for a seasonal epidemic (3% RSV -positive laboratory PCR results).
8Epidemiology of RSV
▪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
▪Work group felt that RSV -associated disease in infants born or entering their
first RSV season is of public health importance
EtRDomain: Benefits and Harms
Do the desirable effects outweigh the undesirable effects?
10Efficacy 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%) None
RSV LRTI with hospitalization 80.6% (95% CI: 62.3% –90.1%) None
RSV LRTI with ICU admission 90.0% (95% CI: 16.4% –98.8%) Serious (imprecision): Too few events
Death due to RSV respiratory
illnessNone recorded N/A
All-cause medically attended -
LRTI34.8% ( 95% CI: 23.0 –44.7%) None
All-cause LRTI -associated
hospitalization44.9% ( 95% CI: 24.9% –59.6%) None
*Pooled phase 2b (excluding underdosed) and phase 3 trial estimate comparing nirsevimab arm to placebo arm
11Relative risk of SAEs and concerns in certainty of
assessment
Outcome Relative risk1 Concerns 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.
12Summary of GRADE for nirsevimab
Outcome Importance Design
(# of studies)Findings Evidence
type1
Benefits
Medically attended RSV
LRTICritical RCT (2)Nirsevimab is effective in preventing medically attended
RSV LRTIHigh
RSV-associted LRTI with
hospitalizationCriticalRCT (2)Nirsevimab is effective in preventing medically attended
RSV LRTI with hospitalization High
RSV-associated LRTI with
ICU admissionCritical RCT (2)Nirsevimab is likely effective in preventing medically
attended RSV LRTI with ICU admissionModerate
RSV-associated death Critical RCT (2) No RSV -associated deaths reported -
All-cause medically
attended LRTIImportantRCT (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 (2)SAEs were likely not more common in intervention group
than placebo groupModerate
13Additional safety data provided at Antimicrobial Drugs
Advisory Committee meeting
▪Most commonly reported adverse reaction were injection site reactions
(0.3%) and rash (0.9%)
▪FDA noted an imbalance in deaths between nirsevimab and the control
arms but determined that the deaths were unlikely to be related to
nirsevimab
https://www.fda.gov/advisory -committees/advisory -committee -calendar/june -8-2023 -meeting -antimicrobial -drugs -advisory -committee -meeting -announcement -06082023
14Nirsevimab phase 3b study (HARMONIE)1
▪Enrolled 8,058 infants
–Age at enrollment: 49% <3 month, 24% 3 -5 months, 28% ≥6 months
–85% born at term, 50% born in season
▪Conducted in France, UK, and Germany during August 8, 2022 –February 28, 2023
▪Randomized to nirsevimab or no injection
▪Primary endpoint RSV hospitalization
–LRTI hospitalization with positive RSV test
–RSV tests ordered by clinician and not on all patients with LRTI
–Participants followed for at least 12 months after randomization
▪At end of RSV season, preliminary efficacy results released
–Median post -randomization follow up time of 2.5 months
1Study not peer reviewed and information provided directly by sponsor; https://www.clinicaltrials.gov/study/NCT05437510
15HARMONIE preliminary results1
▪Efficacy
–RSV hospitalization: 83% (95% CI 68% –92%)
–Severe disease (SaO2 <90% and oxygen given): 76% (95% CI 33% –93%)
–All-cause hospitalization with LRT I during RSV season: 58% (95% CI
40% –71%)
▪Safety
–Grade 1 AEs slightly higher in nirsevimab arm (29%) vs no intervention
arm (25%)
–Number of Grade 2 and Grade 3 AEs similar between nirsevimab and
control arm
SaO2= oxygen saturation; AE= adverse event
1Study not peer reviewed and information provided directly by sponsor; https://www.clinicaltrials.gov/study/NCT05437510/ . Results analyzed as of
2/28/2023 because RSV season had ended, and median duration of follow up was 2.5 months at that time.
16Benefits and harms summary
▪Overall GRADE evidence rating: moderate
▪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
▪The work group felt that the:
–Desirable anticipated effects of nirsevimab were moderate to large
–Undesirable anticipated effects of nirsevimab were minimal to small
–Desirable effects outweighed the undesirable effects and favored
nirsevimab over no intervention
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?
18Summary results of CDC and University of Iowa/RAND
survey on RSV immunizations to prevent RSV disease in
infants
▪Only 33% of respondents thought their baby ‘definitely’ or ‘probably’
would get an RSV infection within one year after being born
▪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)
▪70% of respondents said they ‘definitely’ or ‘probably’ would get an RSV
antibody injection for their baby if safe and effective*
*If antibody injection was approved by FDA and recommended by CDC.
CDC and University of Iowa/RAND survey, unpublished
19Values summary
▪The work group determined that the target population probably feels that the
desirable effects are large relative to undesirable effects
▪The work group varied in whether they felt there was important uncertainty about,
or variability in, how much people value the main outcomes
*If antibody injection was approved by FDA and recommended by CDC.
CDC and University of Iowa/RAND survey, unpublished
EtRDomain: Acceptability
Is immunization with nirsevimab acceptable to key stakeholders?
21Acceptability Summary
▪In a survey of U.S. pediatric providers, over 85% agreed that parents need
more information about RSV, that immunization could help prevent RSV,
and that immunization policy should ensure all children get access1
▪The American Academy of Pediatrics and National Foundation For
Infectious Diseases Roundtable have stated the need for safe and effective
RSV prevention products2,3
▪The work group felt that passive immunization with nirsevimab was
probably acceptable to key stakeholders
1. https://admin.allianceforpatientaccess.org/wp -content/uploads/2023/01/AfPA -and-NCfIH_The -Indirect -Impact -of-RSV_Survey -Report_Ja n-2023.pdf
2. AAP COID BGC Pediatrics 2014 Aug;134(2):415 -20.
3. https://www.nfid.org/wp -content/uploads/2022/04/NFID -RSV-Call-to-Action.pdf
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?
23Work Group Feasibility Interpretation
▪Considerations reviewed in separate presentation
▪Work group felt that nirsevimab will probably be feasible to implement
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?
25Updates to cost effectiveness model
▪Cost of product
–$495 list price
–$395 Vaccines for Children (VFC) program price
–Assuming 50% VFC and 50% private insurance, average price of $445
–Price not final
▪Mortality assumptions modified to include individuals at increased risk of
severe RSV disease
▪Savings from not using palivizumab incorporated
▪Other inputs unchanged1
1Other inputs unchanged from previous model presented at February 23, 2023 ACIP meeting
26Number needed to immunize with nirsevimab to
prevent one health outcome
17 48 128 581
24 194
 - 100 200 300 400 500 600 700
Outpatient ED Inpatient ICU Inpatient Day ICU DayNumber needed to immunize to avoid
27Cost per health event averted
Cost of $445 per dose$2,662 $7,473 $19,909 $90,494
$3,687 $30,165
 $- $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 Day ICU DayCost per Event Averted
28Cost effectiveness result and Work Group
Interpretation
▪Updated base case result: $102,811 per quality adjusted life year saved
▪The work group felt nirsevimab is or probably is a reasonable and efficient
use of resources
EtRDomain: Equity
What would be the impact of nirsevimab on health equity?
30Equity Summary
▪If recommended, ACIP will vote on VFC resolution for nirsevimab
▪National studies of death certificates found higher rates among non -Hispanic black
children compared with non -Hispanic White infants and children aged 1 –4 years1
▪ICU admission rates for RSV among Non -Hispanic Black infants <6 months old were
1.2–1.6x higher than among Non -Hispanic White infants2
▪RSV hospitalization rates 4 –10x higher among Alaska Native and American Indian
children aged <24 months than the rate in the general population3
▪Studies of RSV hospitalization by race and ethnicity have differing results4–7
▪The work group felt that nirsevimab would increase health equity
1. Hansen J Infect Dis 2022 Aug 15;226(Suppl 2):S255 -S266. 2. Unpublished data from RSV -NET, CDC. 3. Atwell Pediatrics 2023, e2022060435. 4 . Hall Pediatrics 2013 Aug;132(2):e341 -8;5. Hall NEJM
2009;360(6):588 –598. 6. Iwane Pediatrics 2004 Jun;113(6):1758 -64, findings differed by age group. 7. Rha Pediatrics 2020 Jul;146 (1):e20193611, findings differed by age group
31EtRSummary: 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?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 to large
Minimal to small
Yes
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?Yes/probably yes
No consensus
Acceptability ▪Is nirsevimab acceptable to key stakeholders? Yes/probably yes
Feasibility ▪Is the intervention feasible to implement? Probably yes
Resource Use ▪Is the intervention a reasonable and efficient allocation of
resources?Yes/probably yes
Equity ▪What would be in the impact of the intervention on health
equity?Probably increased
32Evidence 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
Minority opinion
33Evidence 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 8 –19
months of age with increased risk of severe disease entering their second
RSV season?
35Evidence to Recommendations ( EtR) Framework
PICO Question 2
▪Population Children aged 8 –19 months who are at increased risk of severe RSV
disease and who are entering their second RSV season
Intervention Nirsevimab ( 200 mg [2 x 100 mg] injection near 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 Medically attended LRTI
▪All-cause LRTI associated hospitalization
▪Serious adverse events
36Evidence 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 disease among children who are at increased risk of severe disease
in their 2nd RSV season of public health importance?
38Risk groups previously proposed to receive nirsevimab
when entering second RSV season
▪Based on American Academy of Pediatrics recommendations for palivizumab for a
child’s second RSV season1
▪Assumed to be cost saving compared with palivizumab
▪Proposed recommendation to receive nirsevimab when entering 2nd RSV season
–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 with severe immunocompromise
–Children with cystic fibrosis if manifestations of severe lung disease (previous
hospitalization for pulmonary exacerbation in the first year of life or abnormalities
on chest imaging that persist when stable) or weight for length < 10th percentile
1. American Academy of Pediatrics. Committee on Infectious Diseases [Respiratory Syncitial Virus.] In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds.  Red Book : 2021
Report of the Committee on Infectious Diseases. Itasca, IL: American Academy of Pediatrics, 2021.
39Analyses conducted by CDC to evaluate risk factors for
severe RSV disease during second RSV season
▪Systematic review of literature
▪Analysis of MarketScan national claims database
40Systematic review of literature on risk factors for
severe disease during second RSV season
▪Included any studies that compared RSV hospitalization rates among
children with risk factors to a healthy control group among children aged
6–24 months
▪Among 3,825 abstracts, 6 studies identified
▪Chronic lung disease, congenital heart disease, and neuromuscular disease
analyzed in these studies
▪Studies indicated increased risk of hospitalization for these risk factors
▪No studies evaluating other risk factors identified
41Analysis of MarketScan national claims database for
select risk factors for severe RSV disease during second
RSV season, 2015 -2021
▪Using ICD -9-CM/ICD -10-CM codes, identified children with and without
select conditions (chronic lung disease, congenital heart disease, Down
syndrome, neuromuscular disease, pulmonary malformations,
immunodeficiency, cystic fibrosis) and children that were hospitalized with
RSV
▪Compared rates of RSV hospitalization among children with a chronic
conditions to children without chronic condition
▪Increased rates of hospitalization seen for all conditions
▪RSV testing may be more common for children with risk conditions,
inflating RSV -specific hospitalization rates
42Increased incidence of RSV -associated severe disease
in American Indian and Alaska Native children
1 Atwell 2023 Pediatrics 2023 Jul 14;e2022060435.2Karron et al. J Infect Dis 1999.3Holman et al. Pediatrics 2004. 4Lowther et al. J Ped Infect Dis 20005American Academy of
Pediatrics. Committee on Infectious Diseases [Respiratory Syncytial Virus.] In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds. Red Book : 2021 Report of the Committee
on Infectious Diseases. Itasca, IL: American Academy of Pediatrics, 2021 .▪Several prior studies have documented increased incidence of RSV -associated
hospitalizations among American Indian and Alaska Native children1,2,3,4
–One study found that rates of RSV -associated hospitalization in AI/AN children
were 4 -10 times average rates of U.S. children aged 12 -23 months from NVSN1
–These studies have been conducted in specific populations and may not be
broadly representative of risk in all AI/AN children
–Findings of these studies do not separate environmental, sociocultural, or other
factors that may increase severe disease risk
▪Some AI/AN communities are also in remote areas that make transportation of
children with severe RSV to appropriate healthcare facilities more challenging5
43Public health problem work group interpretation
▪Evidence for RSV burden among children aged 8 –19 months entering their
second with specific risk conditions is limited
▪The work group felt nirsevimab should be recommended to the same
groups that AAP recommends for palivizumab for the second RSV season
▪The work group also felt that nirsevimab should be recommended to
Alaska Native and American Indian children entering their second RSV
season
▪The work group felt that RSV disease among children who are at increased
risk of severe disease1in their 2nd RSV season was of public health
importance
1For groups recommended to receive palivizumab in their second RSV season by the American Academy of Pediatrics and
American Indian and Alaska Native children
EtRDomain: Benefits and Harms
Do the desirable effects outweigh the undesirable effects?
45Efficacy based on extrapolation of pharmacokinetic
data
▪A pharmacokinetic trial was conducted that randomized children at
increased risk of severe RSV disease to palivizumab or nirsevimab
▪In the second RSV season, 220 participants received nirsevimab and 42
received palivizumab
▪Among those that received nirsevimab, two pharmacokinetic endpoints have
been reported
–Day 150 nirsevimab concentrations compared with phase 3 (Melody)
efficacy trial among late pre -term and term infants that showed efficacy
–Proportion of participants that had area under the curve nirsevimab
concentrations above target based on efficacy trial data of 12.8
mg*day/ml
Domachowske J, Madhi SA, Simões EAF, Atanasova V, Cabañas F, Furuno K, et al.  Safety of nirsevimab for RSV in infants with heart or lung disease or prematurity. New
England Journal of Medicine. 2023;386(9): 892 –894. doi: 10.1056/NEJMc2112186
46Observed nirsevimab concentrations 150 days post -dose
▪Among recipients of
nirsevimab, day 150
concentrations higher
in those who received
200 mg in second RSV
season (labeled trial
05) than infants who
received 50mg (if <5kg)
or 100mg (if >5kg) in
phase 3 Melody trial
(labeled trial 04)
Source: FDA briefing document for Antimicrobial Drugs Advisory Committee June 8, 2023 meeting .
The dashed line is EC90 value of 6.8 μg/mL determined based on RSV challenge studies in cotton rat model.
Abbreviations: CHD, hemodynamically significant congenital heart disease; CLD, chronic lung disease of prematurity; EC90, 90% effective
concentration; GA, gestational age. Trial 04: MELODY trial among late pre -term and term infants. Trial 05: Pharmacokinetics stud y among infants at
increased risk of severe RSV disease.
47Area under the curve (AUC) nirsevimab concentration
and safety results
▪Among recipients of nirsevimab in second season, most had AUC
nirsevimab concentrations above the target threshold
–97.7% (129/132) of infants with chronic lung disease
–100% (58/58) of infants with congenital heart disease
▪No adverse events judged as related to nirsevimab or palivizumab in
second RSV season follow up period
Source: FDA briefing document for Antimicrobial Drugs Advisory Committee June 8, 2023 meeting
48Summary of GRADE for nirsevimab dose for second season
Outcome Importance Design
(# of studies)Findings Evidence
type
Benefits
Medically attended (MA)
RSV LRTICritical 1 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 1Prevalence of SAEs was not significantly different in the
intervention and control groupsVery low
49Benefits and harms summary
▪Overall evidence rating: Very low certainty (type 4)
▪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
▪The work group felt1that the:
–Desirable anticipated effects were moderate
–Undesirable anticipated effects were minimal
–Desirable effects outweighed the undesirable effects and favored
nirsevimab over no intervention
1For groups recommended to receive palivizumab in their second RSV season by the American Academy of Pediatrics and
American Indian and Alaska Native children
EtRDomains: Values, Acceptability, and
Feasibility
51Values summary
▪No additional data was available for values specific to populations at
increased risk for severe disease
▪The work group determined that the target population feels or probably
feels that the desirable effects are large relative to undesirable effects1
▪The work group also felt that there was probably not important
uncertainty or variability in how much people valued the main outcomes1
1For groups recommended to receive palivizumab in their second RSV season by the American Academy of Pediatrics and
American Indian and Alaska Native children
52Acceptability summary
▪No additional data was available for acceptability specific to infants and
young children at increased risk
▪The work group felt that prevention with nirsevimab was, or probably was
acceptable to key stakeholders1
1For groups recommended to receive palivizumab in their second RSV season by the American Academy of Pediatrics and
American Indian and Alaska Native children
53Feasibility summary
▪Additional visit to provider might be needed for administration of
nirsevimab prior to beginning of 2nd RSV season
▪The work group felt that nirsevimab was probably feasible to implement
among children aged 8–19 months at increased risk of severe RSV disease
entering their second RSV season1
1For groups recommended to receive palivizumab in their second RSV season by the American Academy of Pediatrics and
American Indian and Alaska Native children
EtRDomain: Resource Use
55Inputs to cost effectiveness model for second RSV
season
▪Theoretical groups of children with increased risk created with 2x, 4x, 6x, 10x
higher risk than the general population aged 8 –19 months in October
–Increased incidence of RSV -associated hospitalization and increased mortality
per hospitalization
–Increased incidence of RSV -associated hospitalization but held mortality per
hospitalization constant
–No increase in incidence of outpatient and ED visits, healthcare costs, or
quality adjusted life years lost with RSV disease1
▪Cost updated to $890 nirsevimab costs (2x $445/dose)
▪Mortality estimates modified to include high -risk individuals
▪Other inputs unchanged1
1Same assumption as previous model presented at February 23, 2023 ACIP meeting
56Updated cost effectiveness results for children 8–19
months entering second RSV season
Incremental Cost -Effectiveness Ratio ($ / quality adjusted life year)
Increased Risk
categoryRSV Hospitalization incidence
increasedRSV hospitalization incidence and
mortality per hospitalization increased
1x (base) $1,557,544 $1,557,544
2x $1,147,756 $836,270
4x $726,983 $280,740
6x $512,337 $118,912
10x $294,775 $25,328
57Resource Use Work Group Interpretation
▪The work group felt that nirsevimab use among children aged 8–19
months entering their second RSV season who are at increased risk of
severe disease1is probably a reasonable and efficient allocation of
resources.
1For groups recommended to receive palivizumab in their second RSV season by the American
Academy of Pediatrics and American Indian and Alaska Native children
EtR Domain: Equity
59Equity summary and Work Group interpretation
▪Equity issues differ by chronic condition among infants and young children
▪AI/AN children have higher hospitalization incidence rates than general population
during second RSV season
▪Non-Hispanic Black and Hispanic populations higher rates of preterm birth than
non-Hispanic White population1
▪The work group felt that nirsevimab use would probably increase health equity2
1https ://www.cdc.gov/reproductivehealth/maternalinfanthealth/pretermbirth.htm
2For groups recommended to receive palivizumab in their second RSV season by the American Academy of Pediatrics and American I ndian
and Alaska Native children
60Summary: Children at high risk entering 2nd RSV season
EtRDomain Question(s) Work Group Judgments
Public Health
Problem▪Is RSV disease among children 8–19 months who are at
increased 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? Yes / Probably yes
Feasibility ▪Is the intervention feasible to implement? Probably yes
Resource Use ▪Is the intervention a reasonable and efficient allocation of
resources?$890: Probably yes
Equity ▪What would be in the impact of the intervention on health
equity?Probably increased
61Evidence to Recommendations Framework
Summary: Work Group Interpretations
Children at increased risk of severe disease entering 2nd RSV season1
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
1For groups recommended to receive palivizumab in their second RSV season by the American
Academy of Pediatrics and American Indian and Alaska Native children
62Evidence to Recommendations Framework
Summary: Work Group Interpretations
Children at increased risk of severe disease entering
2nd RSV season1
Type of
recommendationWe do not
recommend the
interventionWe recommend
theintervention for
individuals based on
shared
clinical decision -
makingWe recommend
theintervention
1For groups recommended to receive palivizumab in their second RSV season by the American
Academy of Pediatrics and American Indian and Alaska Native children
63Acknowledgements
Meredith McMorrow
Lauren Roper
Katherine Fleming -Dutra
Mila Prill
Amanda Payne
Danielle Moulia
Morgan Najdowski
David Hutton
Jamie Pike
Ismael Ortega -Sanchez
Andrew Leidner
Sara Oliver
Monica Godfrey
Evelyn Twentyman
Rebecca Morgan
Doug Campos -Outcalt
Sherry Farr
Karrie Finn -DowningMelissa Glidewell
Eric Griggs
Emilia (Emily) Koumans
Matt Oster
Eghosa (Ivy) Oyegun
Francena Scott
Olga Varechtchouk
Lori Moore
Roua El Kalach
Eric Larson
Harris LaTreace
Michelle Ruslavage
Hannah Rosenblum
James Singleton
Carla Black
Sarah Meyer
Derrell Powers
Raigan WheelerMichael Melgar
Amadea Britton
Erica Reott
Samuel Graitcer
Jeanne Santoli
Jill Moses
Jamie Mells
Dawona Hough
Paul Lucas
Michelle Banks
Arthur Bayo
Nancy Fenlon
Rebecca Miller
Elizabeth Walker
Suzanne Johnson -DeLeon
JoEllen Wolicki
Elizabeth Greene
Neil MurthyPatricia Wodi
Sarah Cutchin
Elisha Hall
Sarah Schillie
Andrew Kroger
Melissa Barnett
Dale Babcock
Rosa Herrera
Richard Quartarone
Stuart Myerburg
Melissa Taylor
Sarah Morales
Barbara Mahon
All members of the ACIP
Mat/Peds RSV Work Group
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.

Back up slides
GRADE
Indication: one dose of nirsevimab for infants aged <8 months born
during or entering their first RSV season
67GRADE: Medically attended RSV LRTI (n=2 studies)
▪Measures of effect
–Efficacy: 79.0% (68.5% to 86.1%)
–Absolute risk (using 23.1% seasonal incidence*): 177 fewer cases per 1,000 immunized
(195 fewer to 152 fewer)
•Number needed to immunize: 6 (5 to 7)
–Absolute risk (using 11.0% seasonal incidence**): 86 fewer cases per 1,000 immunized
(94 fewer to 74 fewer)
•Number needed to immunize: 12 (11 to 14)
–Absolute risk (using 5.4% seasonal incidence [phase 3 trial controls]): 42 fewer cases per
1,000 immunized (46 fewer to 37 fewer)
•Number needed to immunize: 24 (22 to 27)
▪Concerns in certainty assessment
–None
▪Evidence type: High (type 1)67
*Lively 2019 JPIDS , 5 years from 3 NVSN sites from Nov -Apr season, included if with acute respiratory infection (ARI, not
restricted to LRTI).  **Assumes 47.5% of ARI are LRTI ( Rainisch 2020 Vaccine )
68GRADE: RSV -associated LRTI with hospitalization (n=2
studies)
▪Measures of effect
–Efficacy: 80.6% (62.3% to 90.1%)
–Absolute risk (using 1.3% seasonal incidence*): 10 fewer cases per
1,000 immunized (12 fewer to 8 fewer)
•Number needed to immunize: 100 (83 to 125)
–Absolute risk (using 2% seasonal incidence [phase 3 trial controls]): 16
fewer cases per 1,000 immunized (18 fewer to 12 fewer)
•Number needed to immunize: 63 (56 to 83)
▪Concerns in certainty assessment
–None
▪Evidence type: High (type 1)68
*NVSN data 2016 -2020 (unpublished), included if with ARI
69GRADE: RSV -associated LRTI with ICU admission (n=2
studies)
▪Measures of effect
–Efficacy: 90.0% (16.4% to 98.8%)
–Absolute risk (using 0.35% seasonal incidence*): 3 fewer cases per
1,000 immunized (3 fewer to 1 fewer)
•Number needed to immunize: 317 (289 to 1,754)
–Absolute risk (using 0.1% seasonal incidence [phase 3 trial controls]):
0.9 fewer cases per 1,000 immunized (1.0 fewer to 0.2 fewer)
•Number needed to immunize: 1,111 (1,010 to 6,250)
▪Concerns in certainty assessment
–Serious (imprecision): Too few events
▪Evidence type: Moderate (type 2)69
*Arriola 2019 JPIDS for proportion of hospitalizations admitted to ICU, NVSN data 2016 -2020 (unpublished), included if with ARI
70GRADE: All -cause medically attended LRTI (n=2
studies)
▪Measures of effect
–Efficacy: 34.8% (23.0 to 44.7%)
–Absolute risk (using 13.9% seasonal incidence [phase 3 trial controls]):
46 fewer cases per 1,000 immunized (60 fewer to 30 fewer)
•Number needed to immunize: 21 (17 to 33)
▪Concerns in certainty assessment
–None
▪Evidence type: High (type 1)70
71GRADE:  All -cause LRTI -associated hospitalization (n=2
studies)
▪Measures of effect
–Efficacy: 44.9% (24.9% to 59.6%)
–Absolute risk (using 3.7% seasonal incidence in phase 3 controls): 16
fewer cases per 1,000 vaccinated (22 fewer to 9 fewer)
•Number needed to immunize: 63 (45 to 111)
▪Concerns in certainty assessment
▪Evidence type: High (type 1) 71
72GRADE: SAEs (n=2 studies)
▪Measures of effect
–Relative Risk: 0.73 (0.59 to 0.89)
–Absolute risk: 28 fewer cases per 1,000 immunized (43 fewer to 12
fewer)
▪Concerns in certainty assessment
–Serious (imprecision)
▪Evidence type: Moderate (type 2)
72
GRADE
Indication: one dose of nirsevimab for children aged 8 -19 months who are
at increased risk of severe RSV disease and entering their second RSV
season
74GRADE Summary
a Very serious concern for indirectness, due to use of a surrogate outcome, the was surrogate established in 1st season while trial is in 2nd season, and population that does not match proposed indication.
b Pharmacokinetic extrapolation was used and based on comparable pharmacokinetic levels from efficacy in infants <12 months o f age for prevention of the first medically attended RSV LRTI to pharmacokinetic levels in children ≤24
months with chronic lung disease (CLD) or congenital heart disease (CHD) entering their second RSV season. Based on pharmacok inetic and efficacy data from the phase 2b and phase 3 (MELODY) trials, a target area under the curve
nirsevimab concentration of > 12.8 mg*day/ml was established.  For the CLD cohort, 129/132 (98%) participants met the target nirsevimab concentration, and for the CHD cohort, 58/58 (92%) participants met the target. Additionally,
the concentration of nirsevimab 150 days after injection was higher compared with the 150 -day concentration in the phase 3 trial nirsevimab arm population.
c Serious concern for indirectness as the comparison group is palivizumab rather than placebo.
d Very serious concern for imprecision due to the width of the confidence interval containing estimates for which different p olicy decisions might be considered.
e 180 trial participants received nirsevimab in both the first and second season. 40 received palivizumab in the first season and nirsevimab in the second seasonCertainty assessment No of patientsEffect
Certainty Importance
No of
studiesStudy
designRisk of bias Inconsistency Indirectness Imprecision Other
considerationsNirsevimab Palivizumab Relative
(95% CI)Absolute
(95% CI)
Medically attended lower respiratory tract infection
1 randomized
trialnot serious not serious not serious very seriousanone Pharmacokinetic extrapolation
was used and based on
comparable pharmacokinetic
levels from efficacy in infants
<12 months of age for
prevention of the first
medically attended RSV LRTI to
pharmacokinetic levels in
children ≤24 months with
chronic lung disease (CLD) or
congenital heart disease (CHD)
entering their second RSV
seasonbn/a n/a ⨁⨁◯◯
LowCRITICAL
Serious adverse events
1 randomized
trialnot serious not serious seriouscvery seriousdnone 21/220e0/42 (0%) RR 8.4
(0.52 to
135.5)f86 more per
1,000 (from 6
fewer to 1,000
more)g⨁◯◯◯
Very lowImportant
Updated cost effectiveness analysis
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 Michigan
Highlighted portions of presentation represent changes from Feb 2023 ACIP presentation
Research Team
University of Michigan
•David Hutton, PhD
•Lisa Prosser, PhD
•Angela Rose, MPH
•Kerra Mercon , MS•Jefferson Jones, MD, MPH, FAAP
•Mila Prill, MSPH
•Meredith McMorrow, MD, MPH, FAAP
•Jamison Pike, PhD
•Katherine Fleming -Dutra, MD, FAAP
•Ismael Ortega -Sanchez, PhD
•Fiona Havers, MD
•Betsy Gunnels, MSPH
•Andrew Leidner , PhD
77
Conflicts of interest statements
•Authors have no known conflict of interests.
78
Methods: Study question
•Determine the cost -effectiveness of nirsevimab by:
•Evaluating the population burden of disease in pediatric US population in
terms of
•annual resource utilization
•total cases
•total costs
•deaths
•quality -adjusted life years
•Comparing the incremental cost -effectiveness ratio of nirsevimab to no
prevention.
•Running scenario analyses outcomes that explore key areas of
uncertainty.
•Perspective: Societal
79
Methods: Intervention(s)
•Target population: US pediatric < 7 months of age entering their first
RSV season
•Secondary analysis high -risk infants in their second RSV season (7 -18 months
old)
•Interventions:
1.No nirsevimab (Natural history)
2.Nirsevimab against RSV illness
•Time horizon: 1 RSV season
•Analytic horizon: lifetime
•Discount rate: 3%
80
Methods: Decision Tree Model
81No
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
Base 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
82CDC New Vaccine Surveillance Network (NVSN) hospitalization rates for children under 2 years of age from December 2016 to Sep tember 2020 - 1,000 2,000 3,000 4,000
0 2 4 6 8 10 12 14 16 18 20 22Hospitalization rate
per 100,000
children
Age in months
Methods: Epidemiology
ED and Outpatient
Respiratory syncytial virus (RSV)
incidence, per 100,000 Base Case Range 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 –21,600 Lively 2019 (base case and range)5, Hall
2009 (range)6
Age 6 -11 months 24,600 17,700 –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
83
Methods: Epidemiology
Mortality
Base
CaseRange Source
RSV mortality per
hospitalization
Age 0 -5 months0.10% 0.04 -0.20%Hansen 2022,
Doucette 2016
Age 6 -11 months0.10% 0.04 -0.20%Hansen 2022,
Doucette 2016
Age 12 -23 months 0.3%0.28% -0.34%Gupta 2016
84New Mortality estimates are based on recent study by Hansen to be appropriate for
the entire US population instead of just non -high -risk individuals.
Seasonality
0.0%5.0%10.0%15.0%20.0%25.0%30.0%
Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb MarFraction of Annual Infections
85
Source: National Respiratory and Enteric Virus Surveillance System (NREVSS) (2015 -2019)
Methods: Nirsevimab Efficacy
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
Month
86Average efficacy first 6
months = trial efficacy
Sigmoid decay to
final efficacy
Zero efficacy
Methods: Efficacy
Variable Base case
valueRange for
sensitivity
analysisSource
Nirsevimab
Initial efficacy (months 0 -5)
against RSV -associated LRTI 79.0% 68.5% -86.1%
Efficacy months 6 -10 25.0% 0.0% -50.0%
Efficacy after 10 months 0.0%
87
Methods: Provision of Nirsevimab
•Base case:
•At birth for those born
•October 1 –March 31
•October for those born in
•April (~6 -month visit)
•June (~4 -month visit)
•August (~2 -month visit)
•November for those born in
•May (~6 -month visit)
•July (~4 -month visit)
•September (~2 -month visit)
•50% coverage in the population
88
Methods: Medical Costs
Variable Value Range Source
Disease -specific
hospitalization costs (per
hospitalization)
Age 0 -11 months $11,487 4,804 -86,646
Bowser 2022Age 12 -23 months $11,469 4,804 -86,646
Disease -specific ED costs
(per ED visit)$563 544 –581 Bowser 2022
Disease -specific
outpatient costs (per
outpatient visit)$82 46-118 Bowser 2022
89•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
90*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 $445 $50-$600 Assumption
91Both assume no additional visits, but do include costs of administrationManufacturer has suggested $495 list price and $395 for VFC
We assume 50% VFC*
* 50% VFC based on:
Benefits from Immunization During the Vaccines for Children Program Era —United
States, 1994 –2013
Methods: Palivizumab
92•Assumption: Nirsevimab policy will lead to 100% reduction in palivizumab
use.
•Savings assumptions: current Palivizumab use
–1.6% are high -risk (palivizumab -eligible)
–75% uptake in high -risk
–4.17 palivizumab doses/person on average
–$1,228/palivizumab dose
Methods: RSV
Health -Related Quality -of-Life
LRTI 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 13.6
93Measured in
Days Lost
Most
Likely
Methods: Additional Inputs
•Also included nirsevimab adverse events
•Systemic reactions
•Injection site reactions
•Serious adverse events
•Medical costs
•Productivity costs
•Quality -adjusted life -years lost
94
Methods: Uncertainty analyses
•One-way sensitivity
•Scenarios:
•Upper respiratory infection effect
•Timing of administration
•Additional Scenario:
•High -risk children entering the second RSV season
95
Results: Base Case
•Base Case:
•Population of 1,000 births
•50% uptake in the nirsevimab group
•First RSV season
•$500/dose
•Nirsevimab only impacts LRTI
96
Results: Health outcomes
97Cohort:1,000 nirsevimab and 1,000 natural history, assuming 50% uptake in nirsevimab group
URTI -Upper respiratory tract infection; LRTI -Lower respiratory tract infection - 100,000 200,000 300,000 400,000 500,000 600,000 700,000 800,000 900,000
 Natural History  Nirsevimab  Natural History  Nirsevimab  Natural History  Nirsevimab
Outpatient Emergency Department InpatientNumber of Events in Cohort
URTI LRTI
Results: Health outcomes
98Cohort:1,000 nirsevimab and 1,000 natural history, assuming 50% uptake in nirsevimab group107,252.7
38,204.1
14,341.3
3,155.177,442.9
9,465.2
0.020,000.040,000.060,000.080,000.0100,000.0120,000.0
Outpatient ED Inpatient ICU Inpatient Day ICU DayEvents Averted per year
Nirsevimab
Results: Health outcomes
9917 48 128 581
24 194
 - 100 200 300 400 500 600 700
Outpatient ED Inpatient ICU Inpatient Day ICU DayNumber needed to Prophylax to avoid
Nirsevimab
Results: Costs
100Base costs of nirsevimab : $445/dose, Cost of palivizumab for high -risk included in “Natural History”Cohort: 3.66 million births, assuming 50% uptake in nirsevimab group$0$200$400$600$800$1,000$1,200$1,400$1,600$1,800$2,000
Natural
HistoryNirsevimab Natural
HistoryNirsevimab Natural
HistoryNirsevimab Natural
HistoryNirsevimab Natural
HistoryNirsevimab Natural
HistoryNirsevimab
Intervention Outpatient ED Inpatient Deaths TotalTotal Costs in Cohort
Millions
Medical Productivity
Results: Health outcomes
101Base costs of nirsevimab : $445/dose$2,662 $7,473 $19,909 $90,494
$3,687 $30,165
 $- $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 Day ICU DayCost per Event Averted
Nirsevimab
Results: QALYs lost
102Adverse
EventsOutpatient ED Inpatient Deaths Total Grand
Child Caregiver Child Caregiver Child Caregiver Child Child Caregiver Total
Natural History 7,153 3,580 3,290 1,645 807 320 1,356 12,606 5,545 18,151
Nirsevimab 52 6,246 3,127 2,774 1,387 565 224 949 10,586 4,738 15,324
Cohort: 3.66 million births, assuming 50% uptake in nirsevimab group
Results: Cost -effectiveness
103Cohort: 3.66 million births, assuming 50% uptake in nirsevimab group
Base costs of nirsevimab : $445/dose, Cost of palivizumab for high -risk included in “Natural History” $1,550 $1,600 $1,650 $1,700 $1,750 $1,800 $1,850 $1,900
 (18,500)  (18,000)  (17,500)  (17,000)  (16,500)  (16,000)  (15,500)  (15,000)Costs
Millions
QALYs (lost) from RSV
Natural History Nirsevimab
Results: Cost -effectiveness
104OverallCosts ($) QALYsICER ($/QALY)
Vs. NH
Natural History 1,585,172,002 18,151
Nirsevimab 1,875,840,158 15,324 102,811
Cohort: 3.66 million births, assuming 50% uptake in nirsevimab group
Base costs of nirsevimab : $445/dose, Cost of palivizumab for high -risk included in “Natural History”
Sensitivity: Tornado nirsevimab
105Base cost of $445/dose$0 $50,000 $100,000 $150,000 $200,000 $250,000
nirsevimab cost/dose
Disease-specific inpatient costs (per inpatient case)  Age 0-5 months
RSV QALYS Lost
Initial Efficacy
Fraction Receiving Palivizumab Natural History
RSV-related QALYs lost Outpatient Child
Proportion of RSV infections with an LRTI diagnosis Outpatient Age 0-5 months
Disease-specific inpatient costs (per inpatient case)  Age 6-11 months
RSV-related QALYs lost Outpatient Caregiver
Proportion of RSV infections with an LRTI diagnosis Hospitalizations Age 0-5 monthsIncremental Cost -Effectiveness Ratio
Low High
 $- $50,000 $100,000 $150,000 $200,000 $250,000
$0 $100 $200 $300 $400 $500 $600ICER
Total Cost of Nirsevimab (drug + administration)Sensitivity: Cost nirsevimab
106Base cost of $500/dose
Results: Alternative Scenarios
107No Palivizumab
SavingsPalivizumab
Savings
Low -Risk Mortality $205,639 $118,522
Overall Average Mortality $182,397 $102,811
Cohort: 3.66 million births, assuming 50% uptake in nirsevimab group
Base costs of nirsevimab : $445/dose, Cost of palivizumab for high -risk included in “Natural History”
Scenario: Upper respiratory infection effect
108202,821.0
62,596.7
14,341.3
3,155.177,442.9
9,465.2
0.050,000.0100,000.0150,000.0200,000.0250,000.0
Outpatient ED Inpatient ICU Inpatient Day ICU DayEvents Averted per year
Nirsevimab
 $- $50,000 $100,000 $150,000 $200,000 $250,000
$0 $100 $200 $300 $400 $500 $600ICER
Total Cost of Nirsevimab (drug + administration)Scenario: Upper respiratory infection effect
109 Nirsevimab is assumed to be equally efficacious in preventing upper respiratory tract infections as lower respiratory tract infections.$48,208/QALY
Scenario: Timing analysis
110•Cost -effectiveness of an infant receiving nirsevimab as a newborn in
•Oct-Feb
•Oct-March
•Oct-April
•With varying efficacy in months 6 -10
•0%
•25%
•50%
Cohort:1,000 nirsevimab and 1,000 natural history, assuming 50% uptake in nirsevimab group
111Scenario: Timing and efficacy in months 6 -10
Very minor differences, Slightly higher ICERs for Oct -Apr
Base cost of $445/dose
ICER= Incremental cost -effectiveness ratio $- $20,000 $40,000 $60,000 $80,000 $100,000 $120,000
0% efficacy 25% efficacy 50% efficacyICER
Oct-Feb Oct-Mar Oct-Apr
Higher -risk children entering the second RSV
season
112•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
•$890 nirsevimab costs (2x $445/dose)
Cohort:1,000 nirsevimab and 1,000 natural history, assuming 50% uptake in nirsevimab group
Second Season, High -Risk
11301020304050
Inpatient ICU Inpatient Days ICU DaysEvents Averted per 1000
Children given nirsevimabEvents Averted
Base 2x 4x 6x 10x
Second Season, High -Risk
114Cost is $890 per overall course, 2 doses @ $445 eachIncreased
RiskIncidenceIncidence and mortality, given
hospitalization
1x (base) $1,557,544 $1,557,544
2x $1,147,756 $836,270
4x $726,983 $280,740
6x $512,337 $118,912
10x $294,775 $25,328
Limitations
•Model Structure
•No risk groups
•No dynamic transmission. No impact of the vaccine on transmission and
indirect effects
•Uncertain inputs
•Nirsevimab cost
•QALYs lost
•Upper respiratory tract infections
•Palivizumab utilization
115
Summary
•Nirsevimab has the potential to be cost -effective
•Results sensitive to:
•Cost per dose (Cost -Saving –200,000 $/QALY)
•Inpatient costs (Cost -saving –125,000 $/QALY)
•Efficacy (45,000 –170,000 $/QALY)
•URTI/LRTI
•Proportion of infections with LRTI
•Or efficacy of nirsevimab against URTI
•QALYs lost (20,000 –200,000 $/QALY)
•Hospitalization, Outpatient, ED
•Child, Parent
116URTI: Upper Respiratory Tract Infection
LRTI: Lower Respiratory Tract Infection
QALY: Quality -Adjusted Life -Year
Thank You
•Please send comments to:
•dwhutton@umich.edu
117
Appendix
118
Methods: Epidemiological model
119SeasonalityIncidence
•Outpatient
•ED
•Hospitalizations
Nirsevimab
Waning
ProtectionHealth Effects
• Outpatient
• ED
• Hospitalizations
• Deaths
Economic Effects
• Intervention
• Disease
• Societal
• QALYs
• ICERInterventionsEpidemiology
Timing
Cost Burden/
•Outpatient
•ED
•HospitalizationsHealth Economics
Health Burden/
•Outpatient
•ED
•Hospitalizations
Methods: Inputs
•Incidence
•Raw reported incidence may be underreported because of imperfect PCR
sensitivity, so we consider an additional scenario in sensitivity analysis:
•based on CDC Unpublished re -analysis of raw data from Zhang et al study which found
decreased RSV PCR sensitivity in light of paired serology testing (adjustment factor:
87.6%).
120
Methods: Inputs
Variable Value Range Source
Probabilities of Pediatric Adverse
Events: Nirsevimab
Systemic Reaction 0.005 Sanofi/AstraZeneca ACIP
data request
Probability of outpatient visit
given Systemic Reaction1x
Outpatient
Visit- Assumption; Deluca et al
(under review)
Anaphylaxis 0 0 –0.0000010 Sanofi/AstraZeneca ACIP
data request
Injection Site Reaction 0.002 Sanofi/AstraZeneca ACIP
data request
Probability of outpatient visit
given Injection Site Reaction0.1 Assumption; Deluca et al
(under review)
Serious Adverse Event 0.000001 Prosser, 200612
121* ISR grade 3 not reported by arm.  We assumed the ISR grade 3 rates by arm were proportional to ISR of any severity by arm. Range is
based on 95% CI based on binomial proportion from the base value.
Methods: Inputs
Variable Value Range Source
Pediatric Quality -Adjusted Life -
Years lost due to adverse events
Systemic reaction 0.0056 0.00051 -0.0061 Deluca et al (under
review)
Anaphylaxis 0.0137 0.0135 -0.0139
Serious Adverse Event 0.141 0.092 -0.199 (Guillain -Barre) Prosser,
200612
122* No SAEs were reported in the nirsevimab trial. Values in the table above are based on the incidence of Guillian -Barre syndrome
following influenza vaccination.
Methods: Inputs
Variable Value Range Source
Costs due to adverse events^
Medical Costs
Cost of outpatient visit for systemic
reaction$313 $27 -$1,337 Marketscan unpublished;
Deluca et al (under review)
Cost of outpatient visit for injection
site reaction$326 $48 -$1,101 Marketscan unpublished;
Deluca et al (in Press)
Anaphylaxis medical costs $7,706 $89 -$23,414 Marketscan unpublished;
Deluca et al (In Press)
Serious Adverse Event $36,163.76 $10372.31 -$122,145.60 Prosser, 200612
Productivity Costs
Recipient time for office visit (fraction
of day)0.25
Parent time for anaphylaxis (days) 1 1-3 Shimabukuro , 202113
Daily productivity 190 169.41 –211.03 Grosse, 201914
123^ Costs updated to 2022$ using GDP deflator* Daily productivity rate calculated by dividing mean annual total productivity (both market and non -market) for each age group by 365.25 days
Deluca EK, Gebremariam A, Rose A, Biggerstaff M, Meltzer MI, Prosser LA. Cost -Effectiveness of Routine Annual Influenza Vaccination by Age and Risk St atus. Vaccine. 2023. In press
Health -Related Quality -of-Life
•Sources
•Glaser (2022)
•Estimate based on comparison of utility losses between premature children who had RSV vs.
premature children without RSV and their caregivers
•Used as base case for hospitalization for children and their caregivers
•Regnier (2013)
•Estimate QALY losses for hospitalization, ED visits, and outpatient visits for children with
pertussis
•Use relative QALYs between hospitalization, ED, and outpatient to estimate base losses for ED
and outpatient in base case
•JIVE RSV Utilities Survey (2021)
•Estimates QALY losses for hospitalization and outpatient visits for child and caregiver
•Estimates may be impacted by COVID -related concerns about respiratory viruses
•Inform upper bound of range
124
Validation
231
66
8225
65
13
050100150200250
Outpatient Clinic
VisitsED Visits HospitalizationsRates of Medically -Attended RSV
(per 1000 births)
Rainisch et al, Vaccine, 2020 JIVE model
125
Results: Costs
Medical ProductivityIntervention
Outpatient
ED
Inpatient
Total RSV
Medical
Total Health
System
Outpatient
ED
Inpatient
Deaths
Total
Productivity
Total
Natural History 225,005,528 69,409,019 137,189,260 548,601,655 755,199,934 980,205,462 356,863,932 102,733,556 59,598,851 85,770,201 604,966,541 1,585,172,002
Nirsevimab 815,695,065 60,614,296 115,680,370 383,861,494 560,156,160 1,375,851,225 311,646,183 86,626,721 41,701,850 60,014,178 499,988,933 1,875,840,158
126Base cost of $445/doseCohort:entire annual US birth cohort, assuming 50% uptake in nirsevimab group

Summary: Centers for Disease Control and Prevention Evidence to Recommendations Framework:  Nirsevimab Updates Jefferson Jones MD MPH FAAP , CDR USPHS Co-Lead, Respiratory Syncytial Virus Vaccines -Pediatric/Maternal Work Group  Coronavirus and Other Respiratory Viruses Division National Center for Immunization and Respiratory Diseases August 3, 2023 2Evidence to Recommendations ( EtR) Framework Policy Questions ▪Should one dose of nirsevimab be recommended for infants aged <8 months born  during or…


03 RSV Peacock 508

National Center for Immunization & Respiratory Diseases
Centers for Disease Control and Prevention
Nirsevimab : Implementation
Considerations
Georgina Peacock, MD, MPH, FAAP
Director, Immunization Services Division
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention (CDC)
Implementation Considerations
•Definition of Vaccine
•Cost
•Storage and Handling
•Hospital Dosing
•Outpatient Dosing
•Coding and Immunization Information Systems
•Timing of Vaccination
•2nd Year Vaccinations
•Vaccine Administration
•Safety Reporting
•Vaccine Confidence and Demand

•No statutory definition of vaccine in the statute for the Vaccines for Children (VFC) program
(section 1928 of the Social Security Act)
•No statutory definition of vaccine in the Affordable Care Act (section 2713 of PHS Act), or its
implementing regulations, which has a provision that mandates coverage of vaccine
recommendations included on CDC’s immunization schedules
•CDC has determined that nirsevimab is eligible for inclusion in the childhood immunization
schedule and Vaccines for Children programDefinition of “Vaccine”
Program For Distribution Of Pediatric Vaccines
Coverage of Certain Preventive Services Under the Affordable Care Act
•Cost of nirsevimab estimated at $495 per dose in the private sector
•If recommended by ACIP , nirsevimab will be covered by insurance and included in
the VFC program
oImportance of ensuring equitable access to nirsevimab
•However, nirsevimab cost will still be a potential implementation barrier particularly
for ambulatory practices
oIf nirsevimab included in VFC, practices must carry both VFC and private stock,
which may be challenging for some practicesCost
•Similar to other routine vaccines for children
•Administered as intramuscular injection using single -dose pre -filled syringe
oCan be administered simultaneously with other childhood vaccines
•Dosed by weight/age
o50 mg if <5 kg
o100 mg if ≥5 kg
o200 mg (2x100 mg) for high -risk children entering 2ndRSV season
•Stored in refrigerator at 2 -8◦C
•May be kept at room temperature (20 -25◦C) for up to 8 hoursNirsevimab Storage, Handling, and Administration
Source: California Department of Public Health
▪Jurisdictions may have different scope of practice statutes for who can administer
injectable therapeutics vs. vaccines
▪Scan of state laws indicates that most states allow medical assistants (who frequently
administer vaccines) to also deliver injection drugs
oHowever, organizations may have varied practicesScope of Practice Issues
American Association of Medical Assistants
▪Approximately 10% of birthing hospitals participate in the VFC program
▪Bundled payment model for newborn care
oHepatitis B vaccine more feasible to cover at ~$13 –16/dose
oWill nirsevimab be included in bundled payments?
▪Critical to ensure documentation of in -hospital nirsevimab administration in records
sent to primary care provider
oPotential challenges entering nirsevimab in the immunization information
system (IIS)
oComprehensive maternal -neonatal records will become even more critical if
maternal RSV vaccine is licensed and recommendedHospital Administration
CDC Vaccine Price List
•Communication from birthing hospital
•Communication about maternal RSV vaccine
•Initial investment by pediatricians –unsure on price and demand for nirsevimab nor
demand for new product
•Historical lag in insurance payment for new productsOutpatient Administration
•CPT coding and AMA decision around CPT codes —classified as a drug/therapeutic
•Administration codes do not include a counseling component
•Not eligible for stand -alone counseling
•Potential challenges with recording doses in Immunization Information SystemsCoding
Preparing Systems for Administering a Newly Authorized Vaccine
Across the U.S.
Timeline represents standards for vaccines. Incorporating a MAB
into vaccine systems has the potential to expand timeline due to
increased complexity.
Code set subscription services activate. CDSi resources
are published. Provider & payer systems use these for
system development & deployment .Data publication partners
(FDA, CDC, formulary vendors, & AMA)
Prepare & publish vaccine & drug code
set files for systems development
10-12+
Weeks9
WeeksBLA
Approved
2
Weeks3
Weeks4
Weeks5
Weeks6
Weeks1
Week7
Weeks
Provider & payer systems ready to record
& report vaccine administrationIIS systems prepare for
new vaccine codes
6-12+ weeks post authorizationVaccine ready for VTrckS
ordering & distribution
~2 weeks postauthorization8
Weeks
1-4+ weeks post authorization
1-4+ weeks postauthorization
 1-4+ weeks post authorization

•Nirsevimab coded as a therapeutic instead of vaccine could create challenges with:
oInternal provider ordering
oProvision of a vaccine record
oInteroperability/data exchange with electronic health record (EHR) and IIS
•Forecasting (Clinical Decision -Support [CDS] for immunization)
oDosage by weight: CDS does not have access to patient weight
o2ndseason recommendations
oFuture considerations: CDS systems unable to take into account maternal
vaccination history for forecasting for infant nirsevimab immunizationIIS and Vaccine Forecasting Considerations
•Timing of vaccination based on RSV season
oTropical climates may have different/unpredictable seasonality when compared
to most of continental U.S.
•Variability in different localities
oFor example, seasonality in AK less predictable and longer duration
•Second year dosing
oHigh risk populations
oClarifying palivizumab recommendations in the setting of nirsevimab availabilitySpecial Considerations Add Complexity
•Reporting of suspected adverse events (AEs) more complicated for nirsevimab than
other immunizations:
oIf nirsevimab is administered alone, suspected AEs are reported to MedWatch
oIf nirsevimab is administered simultaneously with any vaccine, suspected AEs are
reported to the Vaccine Adverse Event Reporting System (VAERS); additional
reporting to Medwatch not neededReporting of Adverse Events by Patients and Providers
•Will physicians and public accept a new vaccine
•Occurring at the same time as commercialization of COVID -19 vaccine
and seasonal influenza administration
•Vaccine hesitancy and anticipated need for counseling around all
vaccines and products
•Efforts to weaken school immunization requirements and expand
vaccine exemptions at the state levelVaccine Confidence/Demand
•Considerations for implementation
•Risks during this season’s roll out
oTiming of availability of doses
oProvider hesitancy
oUptake
•Complexity of recommendations
oHospital vs. Outpatient
oSeasonality / Timing
oLessons learned with Hepatitis A and B
•Unintended consequencesConclusion and Discussion
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.
Thank You!

Summary: National Center for Immunization & Respiratory Diseases Centers for Disease Control and Prevention  Nirsevimab : Implementation  Considerations Georgina Peacock, MD, MPH, FAAP Director, Immunization Services Division National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention (CDC) Implementation Considerations •Definition of Vaccine •Cost •Storage and Handling •Hospital Dosing •Outpatient Dosing •Coding and Immunization Information Systems •Timing of…


04 RSV Jones 508

Centers for Disease Control and Prevention
Proposed Clinical Consideration Updates for
Nirsevimab
Jefferson Jones MD MPH FAAP , CDR USPHS
Co-Lead, Respiratory Syncytial Virus Vaccines -Pediatric/Maternal Work Group
Coronavirus and Other Respiratory Viruses Division
National Center for Immunization and Respiratory Diseases
August 3, 2023
2Timing of nirsevimab
▪Providers should target administration1:
–In the first week of life for infants born shortly before and during the season
–Shortly before the start of the RSV season for infants aged <8 months
–Shortly before the start of the RSV season for children aged 8 –19 months who
are at increased risk of severe RSV disease
▪Based on pre -pandemic patterns, this means nirsevimab could be administered in
most of the continental United States from October through the end of March
▪Because timing of the onset, peak, and decline of RSV activity may vary, providers
can adjust administration schedules based on local epidemiology
1 While optimal timing for nirsevimab administration is shortly before the season, nirsevimab may be given at any time during t he RSV season for age -
eligible infants and children who have not yet received a dose
3Timing of nirsevimab for infants born shortly before or
during RSV season
▪Nirsevimab should be administered within 1 week of birth.
–Administration can be during the birth hospitalization or in the
outpatient setting
▪Infants with prolonged birth hospitalizations due to prematurity or other
causes should receive nirsevimab shortly before or promptly after
discharge
4Tropical climates and Alaska
▪Tropical climates may have seasonality that differs from most of the
continental United States or is unpredictable
–May include southern Florida, Hawaii, Guam, Puerto Rico, U.S. Virgin
Islands, and U.S. -Affiliated Pacific Islands
▪In Alaska, RSV seasonality is less predictable, and the duration of RSV
seasons is often longer than the national average
▪Providers in these jurisdictions should consult state, local, or territorial
guidance on timing of nirsevimab administration
5Coadministration with routine childhood vaccines
▪In accordance with CDC’s general best practices for immunizations,
simultaneous administration of nirsevimab with age -appropriate vaccines
is recommended
▪In clinical trials, when nirsevimab was given concomitantly with routine
childhood vaccines, the safety and reactogenicity profile of the
coadministered regimen was similar to the childhood vaccines given alone1
▪When coadministered , nirsevimab is not expected to interfere with the
immune response to vaccines2
1FDA label for nirsevimab ; 2Espocito Front Immunol. 2021 Aug 11;12:708939.
6Children aged 8 –19 months recommended to receive
nirsevimab when entering their second RSV season because of
increased risk of severe disease
▪Children with chronic lung disease of prematurity who required medical
support (chronic corticosteroid therapy, diuretic therapy, or supplemental
oxygen) any time during the 6 -month period before the start of the second
RSV season
▪Children with severe immunocompromise
▪Children with cystic fibrosis who have manifestations of severe lung
disease (previous hospitalization for pulmonary exacerbation in the first
year of life or abnormalities on chest imaging that persist when stable) or
weight -for-length <10th percentile
▪American Indian and Alaska Native children
7Nirsevimab recommendations for infants and children
at increased risk of severe RSV
▪Nirsevimab is recommended for infants aged <8 months born during or
entering their first RSV season, including those recommended to receive
palivizumab by AAP1
▪Nirsevimab is recommended for children aged 8 –19 months who are at
increased risk of severe RSV disease and entering their second RSV season,
including those recommended to receive palivizumab by AAP1
▪Per FDA label, children who have received nirsevimab should not receive
palivizumab for the same RSV season2
1American Academy of Pediatrics. Committee on Infectious Diseases [Respiratory Syncytial Virus.] In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds. Red Book
: 2021 Report of the Committee on Infectious Diseases. Itasca, IL: American Academy of Pediatrics, 2021 .
2FDA label for nirsevimab
8Precautions and Contraindications
▪Providers administering nirsevimab should follow ACIP's general best
practice guidelines for immunization1
▪Nirsevimab should not be administered to persons with a history of severe
allergic reaction (e.g., anaphylaxis) after a previous dose or to a product
component (contraindication)
1 For immunization information systems, state or local guidance should be followed
9Consumers and health care providers reporting
suspected adverse reactions for nirsevimab
▪Report suspect adverse reactions following the administration of
nirsevimab without coadministration with any vaccine to MedWatch
–Reports can be submitted to MedWatch online at
www.fda.gov/medwatch or by phone at 1 -800-FDA-1088
▪Report suspect adverse reactions following co -administration of nirsevimab
with any vaccine to the Vaccine Adverse Event Reporting System (VAERS)
–Please specify that the patient received nirsevimab on the VAERS form,
specifically, in Section 9: ‘Prescriptions, over -the-counter medications,
dietary supplements, or herbal remedies being taken at the time of
vaccination’
10Acknowledgements
Meredith McMorrow
Lauren Roper
Katherine Fleming -Dutra
Mila Prill
Amanda Payne
Danielle Moulia
Morgan Najdowski
David Hutton
Jamie Pike
Ismael Ortega -Sanchez
Andrew Leidner
Sara Oliver
Monica Godfrey
Evelyn Twentyman
Rebecca Morgan
Doug Campos -Outcalt
Sherry Farr
Karrie Finn -DowningMelissa Glidewell
Eric Griggs
Emilia (Emily) Koumans
Matt Oster
Eghosa (Ivy) Oyegun
Francena Scott
Olga Varechtchouk
Lori Moore
Roua El Kalach
Eric Larson
Harris LaTreace
Michelle Ruslavage
Hannah Rosenblum
James Singleton
Carla Black
Sarah Meyer
Derrell Powers
Raigan WheelerMichael Melgar
Amadea Britton
Erica Reott
Samuel Graitcer
Jeanne Santoli
Jill Moses
Jamie Mells
Dawona Hough
Paul Lucas
Michelle Banks
Arthur Bayo
Nancy Fenlon
Rebecca Miller
Elizabeth Walker
Suzanne Johnson -DeLeon
JoEllen Wolicki
Elizabeth Greene
Neil MurthyPatricia Wodi
Sarah Cutchin
Elisha Hall
Sarah Schillie
Andrew Kroger
Melissa Barnett
Dale Babcock
Rosa Herrera
Richard Quartarone
Stuart Myerburg
Melissa Taylor
Sarah Morales
Barbara Mahon
All members of the ACIP
Mat/Peds RSV Workgroup
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.

Centers for Disease Control and Prevention
Workgroup Considerations and Voting
Language for Nirsevimab
Jefferson Jones MD MPH FAAP , CDR USPHS
Co-Lead, Respiratory Syncytial Virus Vaccines -Pediatric/Maternal Work Group
Coronavirus and Other Respiratory Viruses Division
National Center for Immunization and Respiratory Diseases
August 3, 2023
13Safety monitoring for nirsevimab
▪FDA will monitor safety reports submitted by patients, providers, and the
manufacturer to the FDA Adverse Event Reporting System (FAERS) and
Vaccine Adverse Event Reporting System (VAERS)
▪FDA will monitor other data sources, including the scientific literature,
applicant’s periodic safety reports, ongoing clinical studies, and potentially
other sources (e.g., medical billing and electronic health records)
▪CDC will monitor reports submitted to VAERS that involve simultaneous
administration of nirsevimab with childhood vaccines and will also monitor
the safety of nirsevimab in the Vaccine Safety Datalink (VSD)
June 8, 2023 Meeting of the Antimicrobial Drugs Advisory Committee -FDA Presentations
14Effectiveness monitoring for nirsevimab
▪ CDC will leverage existing COVID -19 vaccine effectiveness (VE) platforms
▪ New Vaccine Surveillance Network (NVSN)
–Active surveillance network for acute respiratory infection at 7 pediatric medical centers that
can assess effectiveness against outpatient and emergency department visits and
hospitalization
–Capture nirsevimab receipt through parent interview, medical record review at the primary
care provider and birth hospital, and state immunization information systems (IIS)
▪ Virtual SARS -CoV-2, Influenza, and Other respiratory viruses Network (VISION)
–Multi -site, electronic healthcare record -based network that can assess effectiveness against
emergency department/urgent care visits, hospitalization, and critical illness
–Nirsevimab effectiveness analyses will be limited to integrated healthcare system sites that will
have more complete capture of nirsevimab receipt (i.e., through IIS linkage and claims data)
▪ CDC will monitor nirsevimab effectiveness throughout the season, but end of season estimates will
likely be most accurate. Power to estimate effectiveness depends on uptake and RSV incidence
15RSV genomic surveillance
▪Mutations resulting in nirsevimab resistance have been rarely reported1,2
▪Sanofi and AstraZeneca sponsoring INFORM -RSV, a global genomic
surveillance study in children aged < 5 years to monitor evolution of RSV
strains, F protein antigenic sites, and their relationships with clinical
features of RSV disease3
▪CDC planning genomic RSV surveillance of pediatric and adult RSV
specimens, including whole genomic surveillance
–Will monitor for changes in F protein that might result in nirsevimab
resistance
1Ahani et al. Nat Comm 2023 14:4347; 2Wilkins et al. Lancet Infect Dis 2023; 23: 856 –66; 3Tabor 2020 Dec 17;59(1):e01828 -20.
16Work Group considerations for infants aged <8 months
born during or entering RSV season
▪Nirsevimab is safe and effective in reducing the risk of RSV disease, including
hospitalization due to RSV
▪Shared concerns as outlined in implementation considerations presentation
▪Use of nirsevimab would be a reasonable and efficient allocation of resources
–Many work group members prefer lower cost per dose
17Work Group considerations for children aged 8 –19
months who are at increased risk of severe RSV disease
and entering their second RSV season
▪Limited efficacy and safety data for the use of nirsevimab for children in their
second RSV season
▪Limited data on the burden of severe disease in the second RSV season for children
with chronic conditions
▪Support recommendation of nirsevimab being given to children aged 8 –19 months
who are entering their second RSV season for those who are recommended for
palivizumab by American Academy of Pediatrics in their second RSV season and for
American Indian and Alaska Native children
18Proposed ACIP Voting Language
▪Infants aged <8 months born during or entering their first RSV season are
recommended to receive one dose of nirsevimab (50 mg for infants <5 kg
and 100 mg for infants ≥5 kg)
▪Children aged 8–19 months who are at increased risk of severe RSV disease
and entering their second RSV season are recommended to receive one
dose of nirsevimab (200 mg)
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 Proposed Clinical Consideration Updates for  Nirsevimab Jefferson Jones MD MPH FAAP , CDR USPHS Co-Lead, Respiratory Syncytial Virus Vaccines -Pediatric/Maternal Work Group  Coronavirus and Other Respiratory Viruses Division National Center for Immunization and Respiratory Diseases August 3, 2023 2Timing of nirsevimab ▪Providers should target administration1: –In the first week of life for infants born shortly before and during the season –Shortly…


01 RSV Adults Kotton 508

Centers for Disease Control and Prevention
Adult Respiratory Syncytial Virus (RSV) Session
Camille Kotton, MD
Chair, Adult RSV Work Group
Advisory Committee on Immunization Practices (ACIP)
June 21, 2023
2Adult RSV Work Group Membership
ACIP Voting Members
Camille Kotton (Chair)
Keipp Talbot
Sarah Long
Ex Officio Members
Rachel Zhang (FDA)
Judy Beeler (FDA)
Nicholas Geagan (FDA)
Nadine Peart Akindele (FDA)
Sonnie Kim (NIH/NIAID)
Jeffrey Kelman (CMS)
Valerie Marshal (OIDP)CDC Co-Leads
Michael Melgar
Amadea Britton
Consultants
Robert Atmar (Baylor College of
Medicine)
Helen Chu (University of Washington)
Peter Donofrio (Vanderbilt University)
Marie Griffin (Vanderbilt University)Cynthia Lucero -Obusan (Veterans Health
Admin.)
Tracy Ruckwardt (NIH/NIAID)
Jonathan Temte (University of Wisconsin)
Liaisons
Kenneth Schmader (AGS)
Vidya Sundareshan (ACP)
Gretchen LaSalle (AAFP)
April Killikelly (NACI, PHAC)
Winnie Su (NACI, PHAC)Katherine Williams (APTR)
Ruth Lynfield (NFID)
Jennifer Heath (AIM)
Steven Pergam (IDSA)
3CDC Contributors
Coronavirus and Other Respiratory
Viruses Division
Lauren Roper
Fiona Havers
Meredith McMorrow
Diya Surie
Jennifer DeCuir
Mila Prill
Amanda Payne
Natalie Thornburg
Melissa Coughlin
Jefferson Jones
Katherine Fleming -Dutra
Ismael Ortega SanchezImmunization Safety Office
Anne Hause
David Shay
Christine Olson
Immunization Services Division
Neil Murthy
Patricia Wodi
Andrew Leidner
Jamison Pike
4Recap of Adult RSV session, February 2023
▪Economic analysis of RSV vaccination in older adults (CDC model)
▪Comparison of economic analyses of RSV vaccination in older adults (CDC
model vs. industry models)
▪Evidence to Recommendations framework for use of two RSV vaccines
(GSK and Pfizer products) in older adults
5Recent work group discussion
▪Review of Season 2 safety and efficacy data from main phase 3 trials of RSV
vaccines, as well as coadministration study results (with influenza vaccines)
▪Update to GRADE and Evidence to Recommendations for both RSV
vaccines, inclusive of Season 2 data
▪Update to economic analyses of RSV vaccination in older adults, inclusive
of Season 2 data
▪Ethics considerations of different RSV vaccine policy recommendations
6Recent work group discussion
▪Possible policy recommendations for RSV vaccination of U.S. older adults
–Should RSV vaccines be recommended for U.S. adults aged ≥65 years?
–Should RSV vaccines be recommended for U.S. adults aged 60 –64
years?
7Agenda: Wednesday June 21, 2023
▪ Pfizer safety and efficacy update, including coadministration
results
▪ GSK safety and efficacy update, including coadministration
results
▪ Economic analysis of RSV vaccination among U.S. older
adults
▪ Comparison of RSV vaccination economic analyses
performed by U. Michigan/CDC, Pfizer, and GSK
▪ Update to Evidence to Recommendations framework for
Pfizer and GSK RSV vaccines
▪ Clinical considerations for use of RSV vaccines in U.S. older
adultsDr. Alejandra Gurtman (Pfizer)
Dr. Leonard Friedland (GSK)
Dr. David Hutton (U. Michigan)
Dr. Ismael Ortega Sanchez (CDC)
Dr. Michael Melgar (CDC)
Dr. Amadea Britton ( CDC)

Summary: Centers for Disease Control and Prevention Adult Respiratory Syncytial Virus (RSV) Session Camille Kotton, MD Chair, Adult RSV Work Group Advisory Committee on Immunization Practices (ACIP) June 21, 2023 2Adult RSV Work Group Membership ACIP Voting Members Camille Kotton (Chair) Keipp Talbot Sarah Long Ex Officio Members Rachel Zhang (FDA) Judy Beeler (FDA) Nicholas Geagan (FDA) Nadine Peart Akindele (FDA) Sonnie Kim (NIH/NIAID) Jeffrey Kelman (CMS) Valerie Marshal (OIDP)CDC Co-Leads Michael…