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Economics of Preventing Respiratory Syncytial
Virus Lower Respiratory Tract Infections (RSV-
LRTI) among US Infants with Nirsevimab
A SUMMARY REPORT COMPARING MODELS FROM:
Sanofi AND University of Michigan and CDC
Ismael R. Ortega -Sanchez, PhD
NCIRD/CDC
ACIP Meeting, February 23, 2023
46Disclaimer : The findings and conclusions in this report are those of the authors and do not necessarily represent the views of
the Centers for Disease Control and Prevention.
National Center for Immunization & Respiratory Diseases
Conflict of interest
•Sanofi model : Alexia Kieffer et al., [complete authors list and
affiliations, upon request ]
•Sanofi manufactures nirsevimab
•Evidera (San Francisco, London) was funded by Sanofi
•UM-CDC model: David W Hutton et al. from Univ Michigan, …,
I
smael R Ortega -Sanchez et al. from CDC [complete authors list and
affiliations, upon request ]
•All authors: No conflicts of interest
47
Overview
Policy questions:
•Should one dose of nir sevimab be recommended
•a) at birth for all infants born during October to March a nd
•b) for all infants born during April through September and <8
m
onths of age when entering first RSV season?
•Should nirsevimab be recommended for children <20 months of age en
tering their second RSV season who remain at increased risk of
severe disease?
48
Economic analysis
Question: Is the use of nirsevimab against RSV LRTI in all infants <8 months
entering their first RSV season or born during season (and in high- risk children
<20 months entering the 2ndseason) cost-effective ?
Comparator Intervention
Base -case
scenario: What is the incremental cost -effectiveness of using nirsevimab in all
infants <8 months entering their first RSV season or born during season (and in high- risk
children <20 months entering second season) relative to “Standard of Care”?
49Standard of care (SoC)
Infants in first season(and high-risk in 2
nd
season)Giving nirsevimab to
inf
ants in first season
(and hi
gh-risk in 2nd
season)
Standard of Care (SoC) = Palivizumab only for infants eligible as per AAP recommendations, and no immunization for all other pr e-term
and term infants
Focus on key features for model comparison
•Modeling approach
•Targeted population(s)
•Perspective (healthcare vs. societal)
•Intervention strategies and comparators
•Inputs for RSV disease burden, nirsevimab efficacy, and costs
•Incidence of RSV disease, rates of outcomes
•Direct and indirect costs of RSV disease
•Intervention: efficacy, duration of protection, safety and program costs
•Assumptions
•Strong, influential assumptions
50
51Modeling design and assumptions
Sanofi UM-CDC
Static analytical decision -making models ✔ ✔
Sensitivity analyses (and probabilistic simulation) ✔(✔) ✔
Hypothetical population: All infants < 8 months (high risk children 8-19
months)✔(✔) ✔(✔)
Time Frame: First year after a dose of nirsevimab
(2ndseason, 2nd dose for high-risk 8 -19 months only)✔
(✔)✔
(✔)
Analytic Horizon: two years or seasons (for temporary disability) and
Life Expectancy (for premature mortality)✔
✔✔
✔
Discount rate: 3% ✔ ✔
Year of economic outcomes measured: 2022 ✔ ✔
Societal perspective (and healthcare perspective) ✔(✔) ✔(✔)
52Inputs and main outcomes
Prevention of:
•MA RSV LRTI
•RSV LRTI hospitalizations
•RSV-associated deaths
QALYs saved$/QALY saved
Number needed to
immunize (NNI) to avert an:•MA RSV LRTI
•RSV LRTI hospitalization
•RSV-associated deathSanofi UM-CDC
✔ ✔
✔ ✔
✔ ✔
✔ ✔
✔ ✔
✔ ✔
✔ ✔
✔ ✔
HCRU = health care resource use, MA = Medically attended, LRTI= Lower respiratory tract infection, QALY= quality -adjusted life y ear
Sanofi model : Base case estimates for all infants <7
months in Season 1, nirsevimab cost $500/dose & PSA
53Summary outcomes Base-Case
$/QALY gained $70,430
$/RSV MA LRTI case averted $798
$/RSV-associated LRTI
hospitalization averted $9,387
$/RSV-assoc. death averted >$5.6Million
NNI to avert an RSV-MA LRTI
case 5
NNI to avert an RSV-
associated LRTI hospitalization 43
NNI to avert a death 55,957
Probabilistic sensitivity analysis (PSA)
Base case
UM-CDC: Base case estimates for all infants <8
months, Season 1, nirsevimab cost $300/dose
54Cost per type of health outcome prevented Summary outcomes Base-Case
$/QALY gained $102,805
$/RSV-MA LRTI case averted $2,100
$/RSV-associated
LRTI hospitalization averted $18,881
$/RSV-assoc. death averted n/r
NNI avert an RSV -MA LRTI
case 14
NNI avert an RSV -assoc. LRTI
hospitalization 130
NNI avert an RSV -assoc. death n/r
Assuming 100% uptake in nirsevimab group
n/r = not reported$2,528 $7,096 $18,881 $85,822
$3,496 $28,607
$- $10,000 $20,000 $30,000 $40,000 $50,000 $60,000 $70,000 $80,000 $90,000 $100,000
Outpatient ED Inpatient ICU Inpatient
DayICU DayCost per Event Averted
Sanofi and UM-CDC models comparison:
Selected outcome ratios for nirsevimab
55UM- CDC model
Price per dose $300Sanofi model
Price per dose $500
$ / QALY gained
nirsevimab Season 1, infants $102,805 $70,430
nirsevimab Season 2, high risk infants $842,139b$823,131a
nirsevimab Seasons 1 & 2 combined n/r $62,589
nirsevimab vs palivizumab, Season 2 PEPc n/r dominant
$ / hospitalization averted
nirsevimab Season 1 $18,881 $9,387
nirsevimab Seasons 1 & 2 combined n/r $8,316
a. Pre-t erm infants only
b. High risk <19 months old infants (preterm + PEP) receiving a 2nddose of nirsevimab in October
c. PEP= palivizumab eligible population
n/r = not reported
UM-CDC model : One-way Sensitivity Analyses (Season 1 only)
Base case: $102,805/QALY saved, nirsevimab cost $300/dose
56Assuming 100% uptake in nirsevimab group$0 $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000
Nirsevimab cost/dose
RSV QALYs lost Hospitalized RSV QALYS Lost
Initial Efficacy
RSV QALYs lost Outpatient Child
Proportion of RSV infections with an LRTI diagnosis Outpatient Age 0-5 months
RSV QALYs lost Outpatient Child caregiver
Proportion of RSV infections with an LRTI diagnosis Hospitalizations Age 0-5 months
Proportion of RSV infections with an LRTI diagnosis ED Visits Age 0-5 months
RSV QALYs lost ED Child
Proportion of RSV infections with an LRTI diagnosis Outpatient Age 6-11 months
Low HighNirsevimab cost/dose
RSV QALYs lost by a child while hospitalized
Initial vaccine efficacy
RSV QALYs lost by an outpatient’s caregiver
Proportion of RSV infections with an LRTI diagnosis in outpatient visits (age 0 -5 months)
RSV QALYs lost by a child as an outpatient
Proportion of RSV infections with an LRTI diagnosis in hospitalizations (age 0 -5 months)
Proportion of RSV diagnosis in an LRTI diagnosis in ED visits (age 0 -5 months)
RSV QALYs lost by a child as ED patient
Proportion of RSV LRTI diagnosis in outpatients visits (age 6 -11 months)
Sanofi model : One-way Sensitivity Analyses (Season 1 only)
Base case: $70,430/QALY saved, nirsevimab cost $500/dose
57
Sanofi and UM-CDC models comparison:
Selected influential inputs
58•RSV-ho spitalization rate
Sanofi: Age and term -specific hospitalization rates reported in McLaurin (2016)a
UM-CDC: From RSV -associated hospitalization ratesbamong children aged ≤2 years
•Unitary medical cost of RSV hospitalization
Sanofi: Cost varies by term at birth and by whether Intensive Care Unit or Mechanical Ventilator were needed
as reported in McLaurin (2016)b
UM-CDC: Unit cost was a weighted average by term at birth and age as reported in Bowser (2022)c
•RSV season & intervention period
Sanofi: MA RSV season based on Rainisch (2020)dbut intervention ends in February
UM-CDC: RSV-season and intervention period based on CDC surveillance data (2016- 2019)c
•Initial efficacy & waning
Sanofi: Constant first 5 months as in trials, linear decay from month 6 to month 10
UM-CDC: Sigmoid decay up to 10 months; average residual protection in first 5 months equals constant
efficacy from trials
a McLaurin et al. J Perinatol. 2016;36(11):990- 996
b CDC unpublished data from the New Vaccine Surveillance Network (NVSN) (December 2016 to September 2020)
c Bowser et al., J Infect Dis. 2022 Aug 15; 226(Suppl 2): S225– S235
d Rainisch et al. Vaccine . 2020;38(2):251- 257
59UM-CDC Sanofi
Risk of RSV hospitalization (Infants <12
months of age)1.30%
(0.60% - 3.11%)a1.42%
(0.49% - 4.37%)b
Medical costs per RSV hospitalization$11,487
($11,042 - $11,993)c$18,790 – $28,812
(age -and term dependent)d
Medical costs per RSV outpatient visit$82
($46 - $118)c$153
(no variation reported)
a Data from CDC-funded New Vaccine Surveillance Network (NVSN) (December 2016 to September 2020) (range values are the lowest and highest within the first 11 months of age)
b Weighted average term - specific populations shares (range values are the lowest and highest within the first 11 months of age)
c Adapted from Bowser et al., J I nfect Dis . 2022 Aug 15; 226(Suppl 2): S225– S235 (A systematic review study funded by Sanofi)
d Costs in the base - case varied by age, term at birth and by whether Intensive Care Unit or Mechanical Ventilator were needed while hospitalized using percentages as wights; data reported
in McLaurin (2016)Sanofi and UM-CDC models comparison:
Differences in key inputs
Sanofi and UM-CDC models comparison:
Base -case risk of RSV -related hospitalization by age
600.00%0.50%1.00%1.50%2.00%2.50%3.00%3.50%4.00%4.50%5.00%
0 months 1 months 2 months 3 months 4 months 5 months 6 months 7 months 8 months 9 months 10 months 11 monthsRisk of Hospitalization
Age in monthsUM-CDC SanofiUM-CDC model: Laboratory -
confirmed RSV -associated
hospitalization rates from New
Vaccine Surveillance Network (NVSN) data for children under 2 years of age (December 2016 to September 2020)
Sanofi model : Age and term-
specific weighted average of
hospitalization rates in infants using reported rates in McLaurin
(2016)
0%5%10%15%20%25%30%35%Percent of annual cases
Month of seasonUM-CDC
Sanofi
61Sanofi intervention
UM-CDC interventionSanofi and UM-CDC models comparison:
RSV-season and intervention*
Sanofi
InterventionUM- CDC
Intervention
WiS (Within RSV
season). All Infants
born in- season
(i.e., October 1stto
Feb 29th)At birth, if born
October 1st
to
March 31st
WiS: All infants 0 -3
months of age at the
start of RSV season
(i.e., in October)In October, if born in
April
June
August
OoS (Out of RSV
season): All infants
born OoS at the start
of the RSV season
(i.e., in October) In November, if born
in
May
July
September
* RSV -season and Intervention period in UM- CDC model are based on NREVVS seasonality (2016 -2019).
Intervention period in Sanofi model ends in February ( a month short from end of MA RSV season, Rainisch et al., Vaccine . 2020;38(2):251- 257. Technical appendix)
Sanofi and UM-CDC: Initial nirsevimab efficacy
and uptake
62a MELODY trial and Phase 2b recommended dose
b Assumed non- in feriority with palivizumab, Hammitt et al., N Engl J Med. 2022;386(9):837- 846UM-CDC Sanofi
Initial efficacy against MA RSV LRTI:
Inpatient and outpatient (%)a80.0
(68.5 –86.1)a79.0
(68.5 –86.1)a, b
0%20%40%60%80%100%
0 2 4 6 8 10 12Efficacy
Months after immunizationSanofi and UM-CDC: Assumption on duration
of nirsevimab
63SanofiInitial efficacy against MA LRTI = A constant
protection over 5 months, Then, a linear decay of efficacy from month 6 to month 10
No residual protection after 10 months
UM-CDCInitial efficacy against LRTI = Average 5 months
efficacy equals to trial estimatesSigmoid decay up to 10 months and then 0% afterwards;
Calibrated such that the first 5 months efficacy
equals trial estimates
UM-CDC model: comparison of base case &
selected scenarios
64a Base -c ase nirsevimab cost $300 per dose, immunization is for only the 1st season
b
LRTI=Lower respiratory tract infection, URTI= Upper respiratory tract infection
c Cost per QALY saved estimated by varying nirsevimab cost per dose from $200 (low) to $500 (high), immunization is for on ly th e
1stseason Scenario UM-CDC
Nirsevimab cost per $500/dose (1stseason )c$244,677
Intervention period October to February $107,963
Base case a(Nirsevimab cost $300/dose, 1stseason) $102,805
Prevention of All MA RSV visits (LRTI and URTI)b$45,092
Nirsevimab cost per $200/dose (1stseason )c$31,869
Limitations
65•Factors not considered that may result in overestimating the ICER
(underestimating the cost- effectiveness) of nirsevimab immunization
•In base -case: both models assumed
•No protection against URTI
•No protection against asymptomatic/unattended LRTI
•Neither model included RSV- related costs incurred after discharge from an
RSV-associated hospitalization or emergency department visit:
•Productivity losses incurred by caregivers after discharge
•Both models assumed no indirect effects of nirsevimab immunization (i.e., no protection against RSV transmission)
Conclusion
66•Differences in key inputs among Sanofi and UM-CDC models explain differences in results:
•Nirsevimab cost per dose
•Seasonality and intervention period
•Duration of nirservimab efficacy
•Hospitalization rates
•Medical costs
•Base-case in both models:
•Nirsevimab would significantly reduce RSV disease burden in infants
•Data from clinical trials support impact estimates on disease reduction
•Economic value of using nirsevimab in infants could be cost-effective orcostly
•Reasonable nirsevimab price and duration of protection combined with careful design of
seasonal interventions would determine the cost-effectiveness value of routine
prophylaxis among infants ≤7 months of age entering their first RSV season, and those born during the RSV season
Acknowledgements
From NCIRD/CDC
•Jamison Pike
•Jefferson Jones
•Meredith McMorrow
•Mila M. Prill
•Katherine E. Fleming -D utra
•Michael Melgar
Al
so:
•Maternal/Pediatric RSV working group members
67
End of Summary