Document text
Economics of Potential Pentavalent Meningococcal
Conjugate Vaccine (MenABCWY) versus the Current
MenACWY and MenB vaccines for US Adolescents
A SUMMARY REPORT COMPARING MODELS FROM:
Pfizer AND CDC
Ismael R. Ortega-Sanchez, PhD
NCIRD/CDC
Meningococcal ACIP Meeting, October 25, 2023
Disclaimer : The findings and conclusions in this report are t hose of the authors and do not necessarily represen t the views of
the Centers for Disease Control and Prevention.
National Center for Immunization & Respiratory Dise ases
1
Conflict of interest Conflict of interest Conflict of interest Conflict of interest
•Pfizer model : Shannon Sullivan et al., [complete authors list a nd
affiliations, upon request ]
•Pfizer manufactures pentavalent (MenABCWY) vaccine
•Evidera Inc. (France, USA, Hungary) was funded by Pfizer
•CDC model : Ismael R Ortega-Sanchez et al. from CDC [complete
authors list and affiliations, upon request ]
•All authors: No conflicts of interest
2
3 Policy questions for economic modeling 3 Policy questions for economic modeling 3 Policy questions for economic modeling 3 Policy questions for economic modeling •Should the pentavalent vaccine (MenABCWY) be consid ered as an
option for MenACWY/MenB vaccination in people curren tly
recommended to receive both vaccines? (PICO 1)
•Should the pentavalent vaccine (MenABCWY) be include d as an
option for people currently recommended to receive MenACWY only?
(PICO 2)
•Should the pentavalent vaccine (MenABCWY) be includ ed as an
option for people currently recommended to receive MenB only?
(PICO 3)
3
Economic analysis Economic analysis Economic analysis Economic analysis Question : Is vaccinating adolescents 11-16 years old with P entavalent (MenABCWY)
vaccine series to prevent Invasive Meningococcal Di sease in adolescents cost-effective ?
Comparator Interventions
Base-case scenario: What is the incremental cost-effectiveness of vaccinating healthy
adolescents 11-12 and 16 years old with Pentavalent vaccine relative to using MenACWY
and MenB vaccines ? MenACWY vaccine: one dose at 11-12 years and one dose at 16 years. (
Q-Q)
MenB vaccines: two doses at 16 years. (
B-B)Use of Pentavalent
MenABCWY vaccine
combined either as
Q-P-B
P-P-N
or Q-P-P
4
Description of Current and Hypothetical Description of Current and Hypothetical Description of Current and Hypothetical Description of Current and Hypothetical
Vaccines and Vaccination Strategies Vaccines and Vaccination Strategies Vaccines and Vaccination Strategies Vaccines and Vaccination Strategies
Standard of Care (SoC) Potential vaccination strategies
First dose Second dose Key Label First dose Second dose Third dose Key Label
At 11-12 yrs
old with
MenACWY At 16 yrs old
with MenACWY Q-QAt 11-12 yrs old
with MenACWY At 16 yrs old with
MenABCWY At 16.5 yrs old with
MenB Q-P-B
At 11-12 yrs old
with MenABCWY At 16 yrs old with
MenABCWY None (N) P-P-N
At 16 yrs old
with MenB At 16.5 yrs old
with MenB B-BAt 11-12 yrs old
with MenACWY At 16 yrs old with
MenABCWY At 16.5 yrs old with
MenABCWY Q-P-P
SoC= Standard of care (current vaccination programs: Q-Qand B-B)
MenABCWY = Potential pentavalent vaccine ( P) with serogroups A, B, C W Y
MenACWY = currently recommended quadrivalent vaccine ( Q) for serogroups A, C, W, Y,
MenB =currently recommended monovalent vaccine for serogro up B5
Pfizer Pfizer Pfizer Pfizer and and and and CDC CDC CDC CDC : incremental cost : incremental cost : incremental cost : incremental cost- - --effectiveness effectiveness effectiveness effectiveness
analyses of vaccination strategies with pentavalentanalyses of vaccination strategies with pentavalentanalyses of vaccination strategies with pentavalentanalyses of vaccination strategies with pentavalent
Policy
question Incremental
analysis Pfizer CDC Vaccine Price
used for
Pentavalent **
PICO #1 Q- P-B vs SoC Included* Included $250 (private) /
$187.5 (public)
PICO #2 P-P-N vs Q-Q Included Included $210 (private) /
$157.5 (public)
PICO #3 Q- P-Pvs SoC Included Included $210 (private) /
$157.5 (public)
SoC = Standard of care (current vaccination programs: Q-Q and B-B)
* Included in Pfizer technical report updates until August 2023, not inc luded in the Pfizer technical report update of October 2023
** The price of $250 (private) / $187.5 (public) is for strategies using a single dose of pentavalent and the price of $210 (private) / $157.5
(public) for strategies using ≥2 doses of pentavale nt 6
Focus on key features for model comparison Focus on key features for model comparison Focus on key features for model comparison Focus on key features for model comparison •Modeling approach
•Targeted population(s)
•Perspective (healthcare vs. societal)
•Intervention strategies and comparators
•Inputs for IMD burden, vaccine efficacy, and costs
•Incidence of IMD rates and sequelae outcomes
•Direct and indirect costs of IMD
•Intervention: efficacy, duration of protection, saf ety and program costs
•Assumptions
•Strong, influential assumptions
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Modeling design and assumptions Modeling design and assumptions Modeling design and assumptions Modeling design and assumptions
Pfizer CDC
Static analytical decision-making models ✔ ✔
Sensitivity analyses (and probabilistic simulation) ✔(✔)✔(✔)
Hypothetical population: US cohort of adolescents ≥ 11 years of age ✔ ✔
Time Frame: 15 years (from 11-25 years) ✔ ✔
Analytic Horizon: Temporary disability (acute witho ut sequelae) and
Life Expectancy (permanent sequalae or premature mo rtality) ✔
✔✔
✔
Discount rate: 3% ✔ ✔
Year of health and economic outcomes measured: 2022 ✔ ✔
Societal perspective (and healthcare perspective) ✔(✔)✔(✔)
8
Inputs and main outcomes Inputs and main outcomes Inputs and main outcomes Inputs and main outcomes
Prevention of: •IMD cases
•IMD-associated sequelae
•IMD-associated deaths
QALYs saved $/QALY saved Number needed to vaccinate (NNV) to avert an: •IMD case
•IMD death Pfizer CDC
/uni2714 /uni2714/uni2714 /uni2714/uni2714 /uni2714 /uni2714 /uni2714/uni2714 /uni2714
/uni2714/uni2714
IMD = invasive meningococcal disease HCRU = healthcare resource utilization QALY= quality-adjusted life year
9
Pfizer Pfizer Pfizer Pfizer and and and and CDC CDC CDC CDC models comparison: models comparison: models comparison: models comparison:
Selected inputs Selected inputs Selected inputs Selected inputs
•Cost of vaccine and vaccine administration
•IMD incidence for pre vaccine and vaccine era
•Initial vaccine effectiveness and waning over time
•IMD associated permanent sequalae
•Age and serogroup specific Case Fatality Rate (CFR)
•Acute IMD: QALY scores and unitary direct costs
IMD = Invasive meningococcal disease QALY= Quality-adjusted life years
Note : Starting this slide and forward, to specifically identify changes and updates from those presented l ast June 2023, the
text will appear either highlighted, or with the wor d updated at the top of the slide or table. 10
Pfizer Pfizer Pfizer Pfizer vaccine price for a dose of Pentavalent
11 Vaccination
Strategies March to June
2023* August 2023** October 2023***
With one dose
Private $240
($230-$250) $250.0 $250.0
Public -- 187.5 187.5
With ≥ 2 doses
Private $240
($230-$250) $250.0 $210.0
Public -- 187.5 $157.5
* From March to June 2023, Pfizer submitted various technical reports using the pentavalent vaccine prices of $240 (range $230 to $250) per dose
** In August 2023, Pfizer submitted a new technical report updating the penta valent prices to $250 (private) / $187.5 (public) per dose
*** In October 2023, Pfizer submitted a newer technical report updating the pen tavalent prices to $210 (private) / $157.5 (public) per dose for strat egies using ≥2 doses
of pentavalent
Pfizer Pfizer Pfizer Pfizer and and and and CDC CDC CDC CDC : Vaccine cost per vaccine type, : Vaccine cost per vaccine type, : Vaccine cost per vaccine type, : Vaccine cost per vaccine type,
and vaccine administration costs and vaccine administration costs and vaccine administration costs and vaccine administration costs
* 2023 public and private sector cost per dose; VFC Current CDC Vaccine Price List, CDC.
**2023 Proportions of vaccine purchased at private sector and procurement from either private or priva te providers were based on different sources (i.e.,
https://www.cdc.gov/nchs/data/nhis/earlyrelease/ins ur202305_1.pdf , Glazner et al., Pediatrics 2009)
*** Calculated using a hypothetical range of prices for public and private as reported by Pfizer Inc. for MenABCWY .
¶ Assumption considers wastage from either open vi al, mishandling or outdated shelf life.
Note: CDC model : rates and associated costs of hypothetical vaccin e associated adverse events, non shown here, were a pplied to all vaccines.
Trotter et al., BMJ 2002 https://pubmed.ncbi.nlm.nih.gov/11934772/ ; Ortega-Sanchez et al., CID 2008. https://pubmed.ncbi.nlm.nih.gov/18171206/ Quadrivalent (Q)* Men B (B)* Pentavalent (P)
Q-P-B
(single dose) P-P-N & Q- P-P
(≥2 doses)
public sector cost for vaccine $105.6 $141.84 $187.5 $157.5
public sector admin cost $15.0 $15.0 $15.0 $15.0
private sector cost for vaccine $156.0 $211.32 $250.0 $210.0
private sector admin cost $30.0 $30.0 $30.0 $30.0
% vaccine purchased at public sector price ** 53.75% 53.75% 53.75% 53.75%
% vaccinations obtained from private sector provide rs ** 78% 78% 78% 78%
Pfizer : weighted cost per dose + administration $155.61 $ 200.67 $243.11*** $208.48***
% vaccine waste¶ 4.5% 4.5% 4.5% 4.5%
CDC : weighted cost per dose + administration $162.61
($128 - $191) $ 209.70
($155 - $250) $254.05***
($205 - $290) $217.86***
($192 - $250)
12
Pfizer Pfizer Pfizer Pfizer and and and and CDC CDC CDC CDC : Average Annual Incidence in Vaccine : Average Annual Incidence in Vaccine : Average Annual Incidence in Vaccine : Average Annual Incidence in Vaccine
Serogroups BCYW by Age per 100,000 used in the mode ls Serogroups BCYW by Age per 100,000 used in the mode ls Serogroups BCYW by Age per 100,000 used in the mode ls Serogroups BCYW by Age per 100,000 used in the mode ls
Source: CDC Model : Age-by-year-specific data from ABC Core Surveilla nce and NNDSS for PreVaxs and Vax eras
Pfizer model : Pre Vax Era : Mbaeyi et al. Incidence of Meningococcal Disease B efore and After Implementation of Quadrivalent Meni ngococcal Conjugate Vaccine in
the United States. JAMA Pediatr. 2020;174(9):843-8 51. doi:10.1001/jamapediatrics.2020
Vax Era : US CDC Enhanced Meningococcal Disease Surveillanc e Report, 2017. Enhanced Meningococcal Disease Surveillance Report, 2017 (cdc.gov)
Note: Trend and variability across years were used for range of uncertainties and sensitivity analyses •Rates of IMD disease remain relatively higher in late adolescence, but in general rates have been declining for all age groups.
•Overall, IMD incidence rates are
one fifth to
one sixth of those
from recent pre-vaccine era
13
Pfizer Pfizer Pfizer Pfizer and and and and CDC CDC CDC CDC : : : : Initial vaccine effectiveness Initial vaccine effectiveness Initial vaccine effectiveness Initial vaccine effectiveness by by by by
vaccine and serogroup vaccine and serogroup vaccine and serogroup vaccine and serogroup
QUADRIVALENT MEN B PENTAVALENT
Base-case Low High Base-case Low High Base-case Low High
First DOSE MenACWY 93% 73% 98% 93% 73% 98%
2nd + DOSE MenACWY 97% 73% 98% 97% 73% 98%
First DOSE MenB* 60% 18% 74% 60% 18% 74%
2nd + DOSE MenB 85% 50% 99% 85% 50% 99%
Values and assumptions on initial protection are ba sed on various sources:
Phase 3 noninferiority initial vaccine efficacy by single dose (at 11-12yrs) and second-dose (16yrs) o f pentavalent (Men ABCWY) vaccine as reported by Pf izer (data on file).
Updated Pfizer Technical reports on Cost-effectivene ss of the Pentavalent Meningococcal Vaccine (MenABC WY) in the US
Cohn AC, MacNeil JR, Harrison LH, et al. Active Bac terial Core Surveillance (ABCs) Team and MeningNet S urveillance Partners. Effectiveness and Duration of Protection of
One Dose of a Meningococcal Conjugate Vaccine. Pedi atrics. 2017 Feb;139(2):e20162193. doi: 10.1542/ped s.2016-2193. PMID: 28100689; PMCID: PMC8353579.
*The range for VE efficacy for first dose of MenB i s from Castilla et al. NEJM 2023 https://www.nejm.org/doi/full/10.1056/nejmoa2206433
14
Pfizer CDC Pfizer Pfizer Pfizer Pfizer and and and and CDC CDC CDC CDC : : : : Assumption about residual Assumption about residual Assumption about residual Assumption about residual
protection by vaccine and serogroup protection by vaccine and serogroup protection by vaccine and serogroup protection by vaccine and serogroup
Assumptions on residual protection are based on var ious sources:
•Sero-protection is assumed to persist 4-5 years for a single dose of MenACWY and MenABCWY (based on hSBA sero bactericidal assay from Pfizer’s clinical trial s report)
•Pfizer Technical report on Cost-effectiveness of th e Pentavalent Meningococcal Vaccine (MenABCWY) in t he US.
•The pink-shaded areas denote a higher level of unce rtainty of the waning assumption beyond available s urveillance or Phase 3 data
CYW
BB
CYW CYW B
15
Pfizer CDC Pfizer Pfizer Pfizer Pfizer and and and and CDC CDC CDC CDC : : : : Long Long Long Long- - --term sequalae and CFR term sequalae and CFR term sequalae and CFR term sequalae and CFR
included in the models included in the models included in the models included in the models
* Range is a +/- 20% of base-case ** In addition to CFR, it is assumed an increased r isk of excess mortality of
1.21 (1.06-1.37); i.e., reduced life expectancy amo ng survivors with sequalae Long-term sequelae Probability (range for SA)
Skin scarring 7.6
(0 - 19)
Single amputation 1.9
(0.5 - 10)
Multiple amputations 1.2
(0.02 - 6)
Hearing loss 8.8
(2 - 20)
Significant long term neurologic disability 2.1
(0.02 - 11)
28.5% (24.2 - 34.3)* 21.6%
Case Fatality Rate (CFR) For serogroups BCWY Case Fat ality Rate (CFR) For serogroups BCWY
CFR in 11-25 years ** 12.5% (10 to <15yrs)
8% (15 to <25yrs) CFR in 11-25 years*** 12.3%
(8.9 – 15.5)
*** Weighted average by age and serogroup proportio ns (Lower value in
range is from serogroup B, high value is from serog roups CWY).
SA=Sensitivity analysis 16
Pfizer Pfizer Pfizer Pfizer and and and and CDC CDC CDC CDC : Direct costs and QALY scores : Direct costs and QALY scores : Direct costs and QALY scores : Direct costs and QALY scores
used in modeling acute phase of IMD used in modeling acute phase of IMD used in modeling acute phase of IMD used in modeling acute phase of IMD
CDC Pfizer
Direct cost: Medical unitary costs Public health response Medical cost for an IMD acute phase
only $48,983 a
Public response per isolated case
$13,547 Medical cost of IMD acute phase by type d
Meningitis $81,782
Septicemia $115,899
Unspecified $101, 320
IMD cases without permanent sequelae during acute phase Disutility: 0.12 for a year b
Equivalent QALDs: 46.24 days Disutility: 0.4 to 0.51 for a year e
Equivalent QALDs: 146 to 186 days
IMD cases without permanent sequelae after acute phase Disutility: 0.083 for a year c
Equivalent QALDs: 14.8 days Disutility: 0.03 (range +/- 20%) f
Duration: 9 years
Equivalent QALDs: 100 days
a. Medical costs were adjusted to 2022 using the GDP implicit deflator index. Public response costs we re based per hour wage of public health worker, hour s of work
per case, cost of chemoprophylaxis, average number of contacts per case.
b. QALD = quality-adjusted life days lost c. Assumption after acute phase based on 2/3 of disu tility during acute phase for patients without perm anent sequelae
d. Unitary cost per type of IMD based on Davis et a l
https://pubmed.ncbi.nlm.nih.gov/21278486/
e. Derived from Lecocq et al. Vaccine 2016 https://pubmed.ncbi.nlm.nih.gov/27002504/
f. Koomen et al. Qual Life Res. 2005 https://pubmed.ncbi.nlm.nih.gov/16110936/ and Schmand et al J Infect. 2010 https://pubmed.ncbi.nlm.nih.gov/20659499/
17
*Updated from Monte Carlo Simulation using a sample of 1000 iterations. Preliminary estimates. ICER = Increme ntal cost-effectiveness ratio
** Both total net costs estimates relied on $250 (p rivate)/$187.5 (public) cost per dose of pentavalen t vaccine
-10.54 -1.21
5.0% 5.0% 90.0%
0.0 0.2 0.4 0.6 0.8 1.0
-20 -15 -10
-5
05
10
Values in Millions ($) CDC : Cumulative probability of ICER per QALY saved: Q- P-B vs SoC Policy question 1: Policy question 1: Policy question 1: Policy question 1: Pfizer Pfizer Pfizer Pfizer and and and and CDC*: CDC*: CDC*: CDC*: Pentavalent Pentavalent Pentavalent Pentavalent
vaccine price vaccine price vaccine price vaccine price $250 $250 $250 $250 (private)/ (private)/ (private)/ (private)/$187.5 $187.5 $187.5 $187.5 (public)** (public)** (public)** (public)**
Pfizer
Q-P-B vs SoC CDC
Q-P-B vs SoC
IMD cases saved 0 <0 – 5
IMD deaths saved 0 0 – 3
LY saved 0 <0 – 28
QALYs saved 0 <0 – 42
Total Net Costs (millions) ($426)** ($564)**
$/QALY saved Cost savings
($/QALY <0) Cost savings
($/QALY <0) What is the incremental effectiveness and cost-effec tiveness of vaccinating healthy adolescents 11-12 and 16
years old with Pentavalent vaccine relative to using MenACWY and MenB vaccines ?
Baseline: -$3,050,277
18
Policy question 2: Policy question 2: Policy question 2: Policy question 2: Pfizer: Pfizer: Pfizer: Pfizer: Pentavalent Pentavalent Pentavalent Pentavalent vaccine price vaccine price vaccine price vaccine price
$$ $$210 (private)/$157.5 (public)* 210 (private)/$157.5 (public)* 210 (private)/$157.5 (public)* 210 (private)/$157.5 (public)*
P-P-N vs Q-Q
IMD cases saved 41 IMD deaths saved 4 LY saved 86 QALYs saved 164 Total Net Costs (millions)
$319
$/QALY saved $1.94 Million What is the incremental effectiveness and cost-effec tiveness of vaccinating healthy adolescents 11-12 and 16
years old with Pentavalent vaccine relative to using MenACWY only?
ICER = incremental cost-effectiveness ratio LTS = Long-term sequelae
* Updated Pfizer estimates with pentavalent vaccin e price $210 (private)/ $157.5 (Public) and
tornado figure 19
1.73 9.15
5.0% 4.8% 90.2%
0.0 0.2 0.4 0.6 0.8 1.0
0369
12 15
Values in Millions ($) CDC : Cumulative probability of ICER per QALY saved: P- P-N vs Q-QPolicy question 2: Policy question 2: Policy question 2: Policy question 2: CDC*: CDC*: CDC*: CDC*: Pentavalent vaccine price Pentavalent vaccine price Pentavalent vaccine price Pentavalent vaccine price
$210 (private)/$157.5 (public) $210 (private)/$157.5 (public) $210 (private)/$157.5 (public) $210 (private)/$157.5 (public) ** ** ** **
P-P-N vs Q-Q
IMD cases saved 12
IMD deaths saved 1
LY saved 27
QALYs saved 58
Total Net Costs (millions) $270
$/QALY saved $4.7 Million What is the incremental effectiveness and cost-effec tiveness of vaccinating healthy adolescents 11-12 and 16
years old with Pentavalent vaccine relative to using MenACWY only?
Baseline: $4,693,778
*Updated from Monte Carlo Simulation using a sample of 1000 iterations. Preliminary estimates
** Updated Pfizer estimates with pentavalent vacci ne price $210 (private)/ $157.5 (Public) ICER = Inc remental cost-effectiveness ratio 20
Policy question 3: Policy question 3: Policy question 3: Policy question 3: Pfizer Pfizer Pfizer Pfizer and and and and CDC: CDC: CDC: CDC: Pentavalent Pentavalent Pentavalent Pentavalent
vaccine price $210 (private)/$157.5 (public)* vaccine price $210 (private)/$157.5 (public)* vaccine price $210 (private)/$157.5 (public)* vaccine price $210 (private)/$157.5 (public)*
What is the incremental effectiveness and cost-effec tiveness of vaccinating healthy adolescents ≥16 years old
with Pentavalent vaccine relative to using MenB vaccine only ?
Pfizer
Q-P-P vs SoC CDC**
Q-P-P vs SoC
IMD cases saved 4
5
IMD deaths saved 0
0 - 2
LY saved 9 26
QALYs saved 17 39
Total Net Costs (millions) ($528) ($639)
$/QALY saved Cost savings
($/QALY <0) Cost savings
($/QALY <0)
* Updated Pfizer estimates using $210 (private)/$15 7.5 (public) cost per dose of pentavalent vaccine
** Updated from Monte Carlo Simulation using a samp le of 1000 iterations. Preliminary estimates ICER = Incremental cost-effectiv eness ratio
-15.95 -0.58
5.0% 5.0% 90.0%
0.0 0.2 0.4 0.6 0.8 1.0
-20 -15 -10
-5
05
10
Values in Millions ($) CDC : Cumulative probability of ICER per QALY saved: Q- P-P vs SoC
Baseline: -$3,063,131
21
Limitations Limitations Limitations Limitations
•Factors not considered in Pfizer and CDC models that may result in overestimating the ICER
(underestimating the cost-effectiveness) of MenABCW Y
•In base-case: both models assumed
•No protection against non-IMD
•No indirect protection against IMD of unvaccinated individuals
•Productivity losses incurred by caregivers for long -term specific sequelae are based on
assumptions and partially included
•Differences in key inputs among Pfizer and CDC models and the uncertainty in inputs data may expla in
some differences in results:
•Duration of vaccine protection
•Medical costs
•Variability in IMD incidence and CFR data
•Inclusion of different sequalae
•QALY score for IMD cases without permanent sequelae
•Pentavalent price for Q-P-B is uncertain: price used here is the minimum expected. Higher prices will
increase total net cost & ICERs 22
Conclusion Conclusion Conclusion Conclusion
•In both Pfizer and CDC models , MenABCWY vaccine would reduce the IMD burden in adol escents
•In both models, strategies with one or more doses o f the MenABCWY vaccine would save more or equal
number of IMD cases.
•PICO #1 : Q-P-B could be incrementally cost-saving (ICER QALY saved <0) rela tive to SoC
•Q-P-B includes one dose of MenABCWY in substitution o f the second dose of MenACWY and first dose
of MenB
•PICO #2: P-P-N is incrementally costly (not cost saving) relative to Q-Q.
•P-P-N included two doses of MenABCWY in substitution of the two doses of MenACWY ,
•PICO #3: Q-P-P is likely cost saving (ICER QALY saved <0) relative to SoC
•About 96% percent of iterations in the CDC model simulations have an ICER<0
•Q-P-P included two doses of MenABCWY in substitution of the second dose of MenACWY and the first
and second dose of MenB
•Reasonable pentavalent price and duration of protec tion combined with careful design of
vaccination interventions with MenABCWY would determ ine the cost or cost-saving value of the
pentavalent vaccine among adolescents ≥11 year of ag e
23
Acknowledgements Acknowledgements Acknowledgements Acknowledgements
From NCIRD/CDC •Lucy Alexandra McNamara
•Jennifer Collins
•Andrew Leidner
Also: •ACIP Meningococcal working group members
24
End of Summary