Document text
National Center for Immunization & Respiratory Diseases
Evidence to Recommendations Framework:
Pfizer’s MenABCWY Vaccine
Sam Crowe, PhD, MPH
Meningococcal Vaccines Work Group Lead
June 23, 2023
Outline
▪Overview of policy questions and PICOs
▪Evidence to Recommendations framework
▪Summary of findings
▪WG proposed options
2
Pfizer MenABCWY Vaccine
▪Comprised of Trumenba (serogroup B) and Nimenrix (serogroups ACWY)
–Trumenba
•Consists of two purified recombinant lipidated FHbp antigens, one from each FHbp subfamily (A
and B)
•Currently licensed and available in US (10 –25 years)
–Nimenrix
•Meningococcal group A, C, W, and Y polysaccharide tetanus toxoid conjugate vaccine
•Not licensed in US but used extensively in Europe and elsewhere for over a decade
▪Clinical trial data
–Assessed
•Two doses (0,6 m and 0,12 m apart)
–Studied 10 through 25 years of age
–Both MenACWY primed and naïve subjects
–Longer interval studies underway (not available in time for initial product licensure)
3
Policy Questions for 3 PICOs
▪Should the pentavalent vaccine be included as an option for
MenACWY/MenB vaccination in people currently recommended to receive
both vaccines ? (PICO 1)
▪Should the pentavalent vaccine be included as an option for people
currently recommended to receive MenACWY only ? (PICO 2)
▪Should the pentavalent vaccine be included as an option for people
currently recommended to receive MenB only ? (PICO 3)
4
GRADE Table 1: Combined Policy Question and PICO
Policy QuestionShould the pentavalent vaccine be included as an option for people currently recommended to receive
MenACWY and MenB, MenACWY only, or MenB only ?
PopulationAll individuals aged 10 years or older currently recommended to receive MenACWY+MenB, MenACWY , or
MenB vaccine
Intervention Vaccination with the pentavalent vaccine
Comparison Vaccination with currently licensed MenACWY+MenB, MenACWY , or MenB vaccine
Outcomes•Meningococcal disease caused by serogroups A, B, C, W, and Y ( as appropriate by PICO )
•Short -term immunity
•Persistent immunity
•Interference with other recommended vaccines administered concurrently
•Serious adverse events
•Non -serious adverse events
5
Routine Schedule and Increased Risk Populations
▪Routine schedule
–One MenACWY dose at 11 –12 years and a booster at 16 years
–Two MenB doses at 16 –18 years (shared clinical decision -making recommendation)
▪Increased risk, MenACWY (vaccines are interchangeable)
–Recommended for certain medical conditions
•Asplenia, complement deficiency, complement inhibitor use, and HIV infection
–Some microbiologists
–Exposure during an outbreak
–Travel to hyperendemic areas
–First -year college students
–Military recruits
▪Increased risk, MenB (vaccines are notinterchangeable)
–Recommended for certain medical conditions
•Asplenia, complement deficiency, and complement inhibitor use
–Some microbiologists
–Exposure during an outbreak 6
How PICOs Translate into Schedule Options for
Healthy Adolescents
Legend
Q = MenACWY (quadrivalent)
B = MenB
P = MenABCWY (pentavalent) 7Options11–12 year
old dose16 year old
dose #116 year old
dose #2
Standard of care (MenACWY only) Q Q –
Standard of care (MenACWY + MenB) Q Q+B B
PICO 1 (MenABCWY as option for MenACWY + MenB) Q P B
PICO 2 (MenABCWY as option for MenACWY) P P B
PICO 3 (MenABCWY as option for MenB) Q P P
Combination of all 3 PICOs P P P
Public Health Problem
Is meningococcal disease a problem of public health importance?
9Meningococcal Disease Incidence —
United States, 1996 –2022*
0.000.200.400.600.801.001.201.40
1996 2000 2005 2010 2015 2020 2022Incidence per 100,000
Year
Source : 1996 –2022 NNDSS Data. *2021 –2022 NNDSS data are preliminary.0.09 cases/100,000
populationMenACWY vaccine1.2 cases/100,000
population
MenB vaccine
10Average Annual Meningococcal Disease Incidence by
Age Group and Serogroup ― United States, 2010 –2022*
Source: NNDSS data with additional serogroup data from the Active Bacterial Core Surveillance System and state health departm ents
*2022 data are preliminary00.20.40.60.811.2
<1 year 1 year 2-4
years5-10
years11-15
years16-20
years21-25
years26-44
years45-64
years65-84
years85+
yearsIncidence per 100,000
Age GroupB ACWY Oth/Unk
Even with treatment, morbidity and mortality are high
~10–15%
of cases are fatal
11
10–20% of survivors
have permanent sequelaeEven with treatment, mortality and morbidity are high
~10–15%
of cases are fatal
12
Summary of the Public Health Problem
▪Incidence of meningococcal disease
–Low
–Decreasing for some time
▪Causes very severe disease
▪Poor outcomes even with treatment
13
Public Health Problem —Work Group Interpretation
▪Is meningococcal disease a problem of public health importance?
No Probably No Probably Yes Yes Varies Don’t Know
14
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?
GRADE Appendix 1: Studies Included in Review of Evidence
Author, Year Study Design Country AgeNumber of
Participants Number
InterventionNumber
ComparisonData Sources
Pfizer (NCT04440163),
2020RCTUS, Czech R., Denmark,
Hungary, Poland10–25
years2412 1763 649Clinicaltrials.gov,
Pfizer WG and
ACIP
presentations,
Pfizer
correspondence,
Pfizer preliminary
results
presentations Pfizer (NCT03135834),
2017RCTUS, Czech R., Finland,
Poland10–25
years1600 543 1057
Pfizer (NCT04440176),
2020RCT US11–14
years294 294 N/A
16
GRADE Table 2: Outcomes and Rankings
Outcome Importance Included in Profile
Meningococcal disease caused by
serogroups A, B, C, W, and YCritical No
Short -term immunity Critical Yes
Persistent immunity Important Yes
Interference with other recommended
vaccines administered concurrentlyImportant No
Serious adverse events Critical Yes
Non -serious adverse events Important Yes
17
Complexity of Review
▪Four outcomes of interest in evidence profile
–Short -term immunity
–Persistent immunity
–Serious adverse events
–Non -serious adverse events
▪Three PICO questions
–PICO 1: MenABCWY as an option for MenACWY+MenB
–PICO 2: MenABCWY as an option for MenACWY
–PICO 3: MenABCWY as an option for MenB
▪Two populations
–Healthy individuals 10 years old or older
–People with medical conditions that put them at increased risk for invasive disease aged
10 years old or older (i.e., asplenia, complement deficiency, and HIV infection)
18
GRADE Table 4: Short -Term Immunity for Healthy Persons —PICOs 1, 2, and 3
19Certainty assessment № of patients Effect
Certainty Importance
№ of studies Study design Risk of bias Inconsistency Indirectness ImprecisionOther
considerationsPfizer
MenABCWYMenACWY
and MenBRelative
(95% CI)Absolute
(95% CI)
Short -term immunity for MenACWY (follow -up: 1 month)
1 randomized
trialsnot serious not serious serious1not serious none In naïve participants, short -term immunity increases slightly for
serogroups A, C, W, and Y at 1 month after 1 dose of
MenABCWY versus 1 dose of MenACWY -CRM:
Serogroup A (n=753), RR of 1.02 (95% CI: 0.99 –1.05)
Serogroup C (n=753), RR: 1.20 (95% CI: 1.05 –1.38)
Serogroup W (n=736), RR 1.09 (95% CI: 0.99 –1.19)
Serogroup Y (n=742), RR 1.16 (95% CI: 1.06 –1.27)
In primed participants, little or no difference was observed in
short -term immunity for serogroups A, C, W, and Y at 1 month
after 1 dose of MenABCWY versus 1 dose of MenACWY -CRM:
Serogroup A (n=666), RR of 0.98 (95% CI: 0.95 –1.01)
Serogroup C (n=665), RR: 0.99 (95% CI: 0.95 –1.03)
Serogroup W (n=650), RR 1.01 (95% CI: 0.98 –1.04)
Serogroup Y (n=665), RR 1.01 (95% CI: 0.97 –1.05) ⨁⨁⨁◯
ModerateCRITICAL
Short -term immunity for MenB (follow -up: 1 month)
1 randomized
trialsnot serious not serious serious1not serious none 591/755
(78.3%)2263/419
(62.8%)2RR 1.25
(1.15 to 1.36)15,692 more
per 100,000
(from 9,415
more to
22,597 more)⨁⨁⨁◯
ModerateCRITICAL
1hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to exte ndto other
serogroups, but direct evidence for these serogroups is limited. Goldschneider et al. Human immunity to the meningococcus. I. The role of humoral
antibodies. J Exp Med . 1969;129(6):1307 –26.
2Calculated based on serogroup B composite data.
GRADE Table 4: Short -Term Immunity for Persons at Increased Risk —PICOs 1, 2, and 3
20Certainty assessment № of patients Effect
Certainty Importance
№ of studies Study design Risk of bias Inconsistency Indirectness ImprecisionOther
considerationsPfizer
MenABCWYMenACWY
and MenBRelative
(95% CI)Absolute
(95% CI)
Short -term immunity for MenACWY (follow -up: 1 month)
1 randomized
trialsnot serious not serious very
serious1,2not serious none In naïve participants, short -term immunity increases slightly for
serogroups A, C, W, and Y at 1 month after 1 dose of
MenABCWY versus 1 dose of MenACWY -CRM:
Serogroup A (n=753), RR of 1.02 (95% CI: 0.99 –1.05)
Serogroup C (n=753), RR: 1.20 (95% CI: 1.05 –1.38)
Serogroup W (n=736), RR 1.09 (95% CI: 0.99 –1.19)
Serogroup Y (n=742), RR 1.16 (95% CI: 1.06 –1.27)
In primed participants, little or no difference was observed in
short -term immunity for serogroups A, C, W, and Y at 1 month
after 1 dose of MenABCWY versus 1 dose of MenACWY -CRM:
Serogroup A (n=666), RR of 0.98 (95% CI: 0.95 –1.01)
Serogroup C (n=665), RR: 0.99 (95% CI: 0.95 –1.03)
Serogroup W (n=650), RR 1.01 (95% CI: 0.98 –1.04)
Serogroup Y (n=665), RR 1.01 (95% CI: 0.97 –1.05) ⨁⨁◯◯
LowCRITICAL
Short -term immunity for MenB (follow -up: 1 month)
1 randomized
trialsnot serious not serious very
serious1,2not serious none 591/755
(78.3%)3263/419
(62.8%)3RR 1.25
(1.15 to 1.36)15,692 more
per 100,000
(from 9,415
more to
22,597 more)⨁⨁◯◯
LowCRITICAL
1Clinical trials did not include patients at increased risk for invasive disease.
2hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to exte ndto other
serogroups, but direct evidence for these serogroups is limited. Goldschneider et al. Human immunity to the meningococcus. I. The role of humoral
antibodies. J Exp Med . 1969;129(6):1307 –26.
3Calculated based on serogroup B composite data.
GRADE Table 4: Persistent Immunity for Healthy Persons —PICOs 1, 2, and 3
21Certainty assessment № of patients Effect
Certainty Importance№ of studies Study design Risk of bias Inconsistency Indirectness ImprecisionOther
considerationsPfizer
MenABCWYMenACWY
and MenBRelative
(95% CI)Absolute
(95% CI)
Persistent immunity for MenACWY (follow -up: 48 months)
1 randomized
trialsnot serious not serious very
serious1,2not serious none In naïve participants, seroprotection probably increases for
serogroups A, C, W, and Y at 48 months after 2 doses of
MenABCWY versus 54 months after 1 dose of MenACWY -CRM:
Serogroup A (n=112), RR of 1.29 (95% CI: 1.00 –1.67)
Serogroup C (n=113), RR: 1.63 (95% CI: 1.06 –2.49)
Serogroup W (n=111), RR 1.29 (95% CI: 1.05 –1.59)
Serogroup Y (n=113), RR 1.05 (95% CI: 0.98 –1.12)
In primed participants, little or no difference was observed in
seroprotection for serogroups A, C, W, and Y at 48 months after
2 doses of MenABCWY versus 54 months after 1 dose of
MenACWY -CRM:
Serogroup A (n=63), RR of 1.00 (95% CI: 1.00 –1.00)
Serogroup C (n=134), RR: 1.10 (95% CI: 1.01 –1.21)
Serogroup W (n=63), RR 1.10 (95% CI: 0.97 –1.24)
Serogroup Y (n=62), RR 1.00 (95% CI: 1.00 –1.00)⨁⨁◯◯
LowIMPORTANT
Persistent immunity for MenB (follow -up: 48 months)
1 randomized
trialsnot serious not serious serious2not serious none In naïve participants, little or no difference was observed in
seroprotection for serogroup B at 48 months after 2 doses of
MenABCWY versus 48 months after 2 doses of MenB -FHbp :
Serogroup B (A22) (n=233), RR of 0.88 (95% CI: 0.59 –1.31)
Serogroup B (A56) (n=243), RR: 1.17 (95% CI: 0.80 –1.70)
Serogroup B (B24) (n=243), RR 1.38 (95% CI: 0.93 –2.04)
Serogroup B (B44) (n=247), RR 1.13 (95% CI: 0.64 –1.98)⨁⨁⨁◯
ModerateIMPORTANT
1Comparisons were between 2 doses of MenABCWY and 1 dose of MenACWY -CRM. Comparisons also were staggered by 6 months.
2hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to exte ndto other serogroups, but direct
evidence for these serogroups is limited. Goldschneider et al. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med . 1969;129(6):1307 –26.
GRADE Table 4: Persistent Immunity for Persons at Increased Risk —PICOs 1, 2, and 3
22Certainty assessment № of patients Effect
Certainty Importance№ of studies Study design Risk of bias Inconsistency Indirectness ImprecisionOther
considerationsPfizer
MenABCWYMenACWY
and MenBRelative
(95% CI)Absolute
(95% CI)
Persistent immunity for MenACWY (follow -up: 48 months)
1 randomized
trialsnot serious not serious very serious1,2,3 not serious none In naïve participants, seroprotection probably increases for
serogroups A, C, W, and Y at 48 months after 2 doses of
MenABCWY versus 54 months after 1 dose of MenACWY -CRM:
Serogroup A (n=112), RR of 1.29 (95% CI: 1.00 –1.67)
Serogroup C (n=113), RR: 1.63 (95% CI: 1.06 –2.49)
Serogroup W (n=111), RR 1.29 (95% CI: 1.05 –1.59)
Serogroup Y (n=113), RR 1.05 (95% CI: 0.98 –1.12)
In primed participants, little or no difference was observed in
seroprotection for serogroups A, C, W, and Y at 48 months after
2 doses of MenABCWY versus 54 months after 1 dose of
MenACWY -CRM:
Serogroup A (n=63), RR of 1.00 (95% CI: 1.00 –1.00)
Serogroup C (n=134), RR: 1.10 (95% CI: 1.01 –1.21)
Serogroup W (n=63), RR 1.10 (95% CI: 0.97 –1.24)
Serogroup Y (n=62), RR 1.00 (95% CI: 1.00 –1.00)⨁⨁◯◯
LowIMPORTANT
Persistent immunity for MenB (follow -up: 48 months)
1 randomized
trialsnot serious not serious very serious2,3 not serious none In naïve participants, little or no difference was observed in
seroprotection for serogroup B at 48 months after 2 doses of
MenABCWY versus 48 months after 2 doses of MenB -FHbp :
Serogroup B (A22) (n=233), RR of 0.88 (95% CI: 0.59 –1.31)
Serogroup B (A56) (n=243), RR: 1.17 (95% CI: 0.80 –1.70)
Serogroup B (B24) (n=243), RR 1.38 (95% CI: 0.93 –2.04)
Serogroup B (B44) (n=247), RR 1.13 (95% CI: 0.64 –1.98)⨁⨁◯◯
LowIMPORTANT
1Comparisons were between 2 doses of MenABCWY and 1 dose of MenACWY -CRM. Comparisons also were staggered by 6 months.
2Clinical trials did not include patients at increased risk for invasive disease.
3hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to exte ndto other serogroups, but direct
evidence for these serogroups is limited. Goldschneider et al. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med . 1969;129(6):1307 –26.
GRADE Table 4: Serious Adverse Events for Healthy and Increased Risk —PICOs 1,
2, and 3
231 Comparisons were between 2 doses of MenABCWY and 1 dose of MenACWY -CRM plus 2 doses of MenB -FHbp .
2Downgraded because relative effect confidence intervals are wide.
3Clinical trials did not include patients at increased risk for invasive disease. Certainty assessment № of patients Effect
Certainty Importance
№ of studies Study design Risk of bias Inconsistency Indirectness ImprecisionOther
considerationsPfizer
MenABCWYMenACWY
and MenBRelative
(95% CI)Absolute
(95% CI)
2 randomized
trialsnot serious not serious serious1serious2none 13/2306
(0.6%) 8/1706 (0.5%) RR 1.94
(0.72 to 5.22)441 more per
100,000
(from 131
fewer to 1979
more)⨁⨁◯◯
LowCRITICALHealthy Persons
Persons at Increased Risk
Certainty assessment № of patients Effect
Certainty Importance
№ of studies Study design Risk of bias Inconsistency Indirectness ImprecisionOther
considerationsPfizer
MenABCWYMenACWY
and MenBRelative
(95% CI)Absolute
(95% CI)
2 randomized
trialsnot serious not serious very
serious1,3Serious2none 13/2306
(0.6%) 8/1706 (0.5%) RR 1.94
(0.72 to 5.22)441 more per
100,000
(from 131
fewer to 1979
more)⨁◯◯◯
Very lowCRITICAL
GRADE Table 4: Non -Serious Adverse Events Healthy and Increased Risk —PICOs
1, 2, and 3
Healthy Persons
Persons at Increased Risk
241Comparisons were between 2 doses of MenABCWY and 1 dose of MenACWY -CRM plus 2 doses of MenB -FHbp .
2Downgraded because absolute effect confidence intervals are wide.
3Clinical trials did not include patients at increased risk for invasive disease. Certainty assessment № of patients Effect
Certainty Importance№ of studies Study design Risk of bias Inconsistency Indirectness ImprecisionOther
considerationsPfizer
MenABCWYMenACWY
and MenBRelative
(95% CI)Absolute
(95% CI)
Non -serious adverse events (assessed with: All adverse events through 1 month after 2nd vaccination)
2 randomized
trialsnot serious not serious serious1serious2none 581/2306
(25.2%) 387/1706
(22.7%) RR 1.31
(1.17 to 1.47)7,032 more
per 100,000
(from 3,856
more to
10,662 more)⨁⨁◯◯
LowIMPORTANT
Certainty assessment № of patients Effect
Certainty Importance№ of studies Study design Risk of bias Inconsistency Indirectness ImprecisionOther
considerationsPfizer
MenABCWYMenACWY
and MenBRelative
(95% CI)Absolute
(95% CI)
Non -serious adverse events (assessed with: All adverse events through 1 month after 2nd vaccination)
2 randomized
trialsnot serious not serious Serious1,3serious2none 581/2306
(25.2%) 387/1706
(22.7%) RR 1.31
(1.17 to 1.47)7,032 more
per 100,000
(from 3,856
more to
10,662 more)⨁◯◯◯
Very lowIMPORTANT
25Benefits and Harms —Work Group Interpretation
▪How substantial are the desirable anticipated effects?
Minimal Small Moderate Large Varies Don’t KnowPICO 1 (MenABCWY as an option for MenACWY+MenB)
PICO 3 (MenABCWY as an option for MenB)PICO 2 (MenABCWY as an option for MenACWY)
Minimal Small Moderate Large Varies Don’t Know
Minimal Small Moderate Large Varies Don’t Know
26Benefits and Harms —Work Group Interpretation
▪How substantial are the undesirable anticipated effects?
Minimal Small Moderate Large Varies Don’t KnowPICO 1 (MenABCWY as an option for MenACWY+MenB)
PICO 3 ( MenABCWY as an option for MenB )PICO 2 ( MenABCWY as an option for MenACWY )
Minimal Small Moderate Large Varies Don’t Know
Minimal Small Moderate Large Varies Don’t Know
27Benefits and Harms —Work Group Interpretation
▪Do the desirable effects outweigh the undesirable effects?
Favors
interventionFavors
comparisonFavors both Favors neither Varies Don’t KnowPICO 1 ( MenABCWY as an option for MenACWY+MenB )
PICO 3 ( MenABCWY as an option for MenB )PICO 2 ( MenABCWY as an option for MenACWY )
Favors
interventionFavors
comparisonFavors both Favors neither Varies Don’t Know
Favors
interventionFavors
comparisonFavors both Favors neither Varies Don’t Know
Values
-Does the target population feel that the desirable effects are large relative to
undesirable effects?
-Is there important uncertainty about or variability in how much people value
the main outcomes?
Perspective of the Target Population
▪Limited data are available on values of the target population toward
inclusion of the pentavalent vaccine
▪In 2021, vaccination coverage of at least 1 dose was 89% for MenACWY
and 31% for MenB among adolescents
▪Limited data are available on vaccine uptake in other individuals
recommended to receive MenACWY or MenB vaccine
29
Reduced Doses
▪“Use of combination vaccines can reduce the number of injections patients receive
and alleviate concern associated with the number of injections… The use of a
combination vaccine generally is preferred over separate injections of the
equivalent component vaccines. Considerations should include provider
assessment, patient preference, and the potential for adverse events.”1
▪“Combination vaccines represent one solution to the issue of increased numbers
of injections during single clinic visits and generally are preferred over separate
injections of equivalent component vaccines.”2
1 General Best Practice Guidelines for Immunization. Best Practice Guidance of the ACIP. https://www.cdc.gov/vaccines/hcp/acip -recs/general -
recs/downloads/general -recs.pdf
2 American Academy of Pediatrics. Red Book 2018. Report of the Committee on Infectious Diseases. 31stEd. https://seciss.facmed.unam.mx/wp -
content/uploads/2021/02/Red -Book -31th -Edition.pdf 30
Values —Work Group Interpretation
▪Does the target population feel that the desirable effects are large relative to undesirable effects?
No Probably No Probably Yes Yes Varies Don’t KnowPICO 1 ( MenABCWY as an option for MenACWY+MenB )
PICO 3 ( MenABCWY as an option for MenB )PICO 2 ( MenABCWY as an option for MenACWY )
No Probably No Probably Yes Yes Varies Don’t Know
No Probably No Probably Yes Yes Varies Don’t Know
31
Uncertainty in How People Value the Outcomes
▪Limited data available on how much people value the main outcomes
▪Vaccination rates for MenACWY , a routine recommendation, are high
among the target population
▪Vaccination rates for MenB are considerably lower, but decisions to
vaccinate are based on shared clinical decision -making
–Cause for lower rates unclear: lack of interest in vaccination, lack of awareness
of option?
32
Values —Work Group Interpretation
▪Is there important uncertainty about or variability in how much people value the main outcomes?
Important
uncertainty or
variabilityProbably important
uncertainty or
variabilityProbably not
important
uncertainty or
variabilityNo important
uncertainty or
variabilityNo known
undesirable
outcomesPICO 1 ( MenABCWY as an option for MenACWY+MenB )
PICO 3 ( MenABCWY as an option for MenB )PICO 2 ( MenABCWY as an option for MenACWY )
Important
uncertainty or
variabilityProbably important
uncertainty or
variabilityProbably not
important
uncertainty or
variabilityNo important
uncertainty or
variabilityNo known
undesirable
outcomes
Important
uncertainty or
variabilityProbably important
uncertainty or
variabilityProbably not
important
uncertainty or
variabilityNo important
uncertainty or
variabilityNo known
undesirable
outcomes
33
Acceptability
-Is the intervention acceptable to key stakeholders?
35Stakeholder Acceptability
▪Limited data are available on the acceptance among key stakeholders of including MenABCWY
as an option in the current vaccination schedule
▪Proponents for increasing MenB vaccination likely would be supportive
–Pentavalent vaccine combines MenB (a shared clinical decision -making recommendation)
with MenACWY (a standard recommendation)
–Could increase vaccination rates against serogroup B
▪Patients who seek vaccination against all 5 serogroups also might be supportive due to the
reduced number of doses needed (4 versus 3)
▪Health care providers might be supportive, particularly if they could stock fewer vaccines1,2
1CDC. Timing and Spacing of Immunobiologics : General Best Practice Guidelines for Immunization. ACIP Timing and Spacing Guidelines
for Immunization | CDC .
2Hall E, Odafe S, Madden J, Schillie S. Qualitative Conceptual Content Analysis of COVID -19 Vaccine Administration Error Inquiries.
Vaccines . 2023; 11(2):254.
36Acceptability —Work Group Interpretation
▪Is the intervention acceptable to key stakeholders?
No Probably Probably Yes Yes Varies Don’t KnowPICO 1 (MenABCWY as an option for MenACWY+MenB)
PICO 3 (MenABCWY as an option for MenB)PICO 2 (MenABCWY as an option for MenACWY)
No Probably No Probably Yes Yes Varies Don’t Know
No Probably No Probably Yes Yes Varies Don’t Know
Resource Use
-Is the intervention a reasonable and efficient allocation of resources?
38CDC Cost Effectiveness Model Summary
▪Weighted cost per dose + administration
–MenACWY: $163 ($128 –$191)
–MenB: $210 ($155 –$250)
–MenABCWY: $278 ($255 –$290)
•Most MenABCWY strategies would save more or the same number of cases as the
standard of care, but they would do so at a much higher cost perQALY saved
•The exception is the Q -P-B, which could be incrementally cost saving (ICER QALY <0)
relative to the standard of care
39Resource Use —Work Group Interpretation
▪Is the intervention a reasonable and efficient allocation of resources?
No Probably No Probably Yes Yes Varies Don’t KnowPICO 1 (MenABCWY as an option for MenACWY+MenB)
PICO 3 (MenABCWY as an option for MenB)PICO 2 (MenABCWY as an option for MenACWY)
No Probably No Probably Yes Yes Varies Don’t Know
No Probably No Probably Yes Yes Varies Don’t Know
Equity
-What would be the impact on health equity?
41Equity Considerations
▪Limited data are available on the impact of the pentavalent vaccine on health
equity
▪It is not expected that the vaccine will negatively impact equity
▪It could potentially reduce disparities among those who might be interested in
being vaccinated against serogroup B but who might not receive clinical care that
includes discussion of the MenB vaccine
42Equity —Work Group Interpretation
▪What would be the impact on health equity?
ReducedProbably
ReducedProbably No
ImpactProbably
IncreasedIncreased Varies Don’t KnowPICO 1 (MenABCWY as an option for MenACWY+MenB)
PICO 3 (MenABCWY as an option for MenB)PICO 2 (MenABCWY as an option for MenACWY)
ReducedProbably
ReducedProbably No
ImpactProbably
IncreasedIncreased Varies Don’t KnowReducedProbably
ReducedProbably No
ImpactProbably
IncreasedIncreased Varies Don’t Know
Feasibility
-Is the intervention feasible to implement?
44Feasibility Considerations
▪Challenges with insurance coverage specific to the pentavalent vaccine not expected
▪Substantial financial burdens for providers or health systems not expected
▪Pentavalent vaccine likely would be easily integrated into providers' practices
–Would provide additional option in current schedule
–Administration of the pentavalent vaccine is of equal complexity as currently available vaccines
–Barriers to stocking the pentavalent vaccine not expected
–Unclear, however, whether providers are willing to stock three different vaccine types
▪Providers who routinely vaccinate persons aged 16 –18 years might have an incentive to stock the
vaccine to reduce the number of doses given to patients who prefer vaccination against all 5
serogroups
45Feasibility —Work Group Interpretation
▪Is the intervention feasible to implement?
No Probably No Probably Yes Yes Varies Don’t KnowPICO 1 (MenABCWY as an option for MenACWY+MenB)
PICO 3 (MenABCWY as an option for MenB)PICO 2 (MenABCWY as an option for MenACWY)
No Probably No Probably Yes Yes Varies Don’t Know
No Probably No Probably Yes Yes Varies Don’t Know
Summary
47EtR Summary for PICO 1 (MenABCWY as an option for MenACWY+MenB)
Domain Question Work Group Judgment
Public health problem Is meningococcal disease a public health problem? Yes
Benefits and harmsHow substantial are the desirable anticipated effects? Small
How substantial are the undesirable anticipated effects? Small
Do the desirable effects outweigh the undesirable effects? Favors intervention
What is the overall certainty of the evidence profile? Varies by group
ValuesDoes the target population feel the desirable effects are large relative to
the undesirable effects? Probably yes
Is there important uncertainty about or variability in how much people
value the main outcomes? Probably not important
uncertainty or variability
Acceptability Is the intervention acceptable to key stakeholders? Probably yes or yes
Resource use Is the intervention a reasonable and efficient allocation of resources? Probably yes or yes
Equity What would be the impact on health equity? Probably no impact or
varies
Feasibility Is the intervention feasible to implement? Probably yes or yes
48Balance of Consequences —PICO 1 (MenABCWY as an option for
MenACWY+MenB)
Undesirable
consequences
clearly outweigh
desirable
consequences in
most settings Undesirable
consequences
probably outweigh
desirable
consequences in
most settingsThe balance
between
desirable and
undesirable
consequences is
closely balanced
or uncertainDesirable
consequences
probably outweigh
undesirable
consequences in
most settingsDesirable
consequences
clearly outweigh
undesirable
consequences in
most settingsThere is
insufficient
evidence to
determine the
balance of
consequences
Is there sufficient information to move forward with a recommendation?
Yes No
49EtR Summary for PICO 2 (MenABCWY as an option for MenACWY)
Domain Question Work Group Judgment
Public health problem Is meningococcal disease a public health problem? Yes
Benefits and harmsHow substantial are the desirable anticipated effects? Minimal, small, or
moderate
How substantial are the undesirable anticipated effects? Minimal or small
Do the desirable effects outweigh the undesirable effects? Favors intervention,
comparison, or both
What is the overall certainty of the evidence profile? Varies by group
ValuesDoes the target population feel the desirable effects are large relative to
the undesirable effects? Probably yes
Is there important uncertainty about or variability in how much people
value the main outcomes? Probably important
uncertainty or variability
Acceptability Is the intervention acceptable to key stakeholders? Probably yes or yes
Resource use Is the intervention a reasonable and efficient allocation of resources? Probably no or no
Equity What would be the impact on health equity? Probably increased, varies,
or don’t know
Feasibility Is the intervention feasible to implement? Probably yes or yes
50Balance of Consequences —PICO 2 (MenABCWY as an option for
MenACWY)
Undesirable
consequences
clearly outweigh
desirable
consequences in
most settings Undesirable
consequences
probably outweigh
desirable
consequences in
most settingsThe balance
between
desirable and
undesirable
consequences is
closely balanced
or uncertain Desirable
consequences
probably outweigh
undesirable
consequences in
most settingsDesirable
consequences
clearly outweigh
undesirable
consequences in
most settingsThere is
insufficient
evidence to
determine the
balance of
consequences
Is there sufficient information to move forward with a recommendation?
Yes No
51EtR Summary for PICO 3 (MenABCWY as an option for MenB)
Domain Question Work Group Judgment
Public health problem Is meningococcal disease a public health problem? Yes
Benefits and harmsHow substantial are the desirable anticipated effects? Minimal
How substantial are the undesirable anticipated effects? Minimal to small
Do the desirable effects outweigh the undesirable effects? Favors intervention or
comparison
What is the overall certainty of the evidence profile? Varies by group
ValuesDoes the target population feel the desirable effects are large relative to
the undesirable effects? Probably yes or don’t know
Is there important uncertainty about or variability in how much people
value the main outcomes? Important or probably
important
Acceptability Is the intervention acceptable to key stakeholders? Don’t know
Resource use Is the intervention a reasonable and efficient allocation of resources? Probably yes or yes
Equity What would be the impact on health equity? Don’t know
Feasibility Is the intervention feasible to implement? Probably yes or yes
52Balance of Consequences —PICO 3 (MenABCWY as an option for MenB)
Undesirable
consequences
clearly outweigh
desirable
consequences in
most settings Undesirable
consequences
probably outweigh
desirable
consequences in
most settingsThe balance
between
desirable and
undesirable
consequences is
closely balanced
or uncertain Desirable
consequences
probably outweigh
undesirable
consequences in
most settings Desirable
consequences
clearly outweigh
undesirable
consequences in
most settings There is
insufficient
evidence to
determine the
balance of
consequences
Is there sufficient information to move forward with a recommendation?
Yes No
Proposed Options
54Work Group Interpretation, PICO 1
We do not recommend the intervention, but it may be used within FDA licensed indications
We recommend the intervention for individuals based on shared clinical decision -making
We recommend the intervention▪Should the pentavalent vaccine be included as an option for MenACWY/MenB
vaccination in people currently recommended to receive both vaccines ?
55Work Group Interpretation, PICO 2
We do not recommend the intervention, but it may be used within FDA licensed indications
We recommend the intervention for individuals based on shared clinical decision -making
We recommend the intervention▪Should the pentavalent vaccine be included as an option for people
currently recommended to receive MenACWY only ?
56Work Group Interpretation, PICO 3
We do not recommend the intervention, but it may be used within FDA licensed indications
We recommend the intervention for individuals based on shared clinical decision -making
We recommend the intervention▪Should the pentavalent vaccine be included as an option for people
currently recommended to receive MenB only ?
▪WG was divided on this option, but a small majority were in favor of not
proposing
▪WG agreed to have ACIP consider the strengths and weaknesses of this
option
Schedule Options
Legend
Q = MenACWY (quadrivalent)
B = MenB
P = MenABCWY (pentavalent) 57Options11–12 year
old dose16 year old
dose #116 year old
dose #2WG
Decision
Standard of care (MenACWY only) Q Q – N/A
Standard of care (MenACWY + MenB) Q Q+B B N/A
PICO 1 (MenABCWY as option for MenACWY + MenB) Q P B
PICO 2 (MenABCWY as option for MenACWY) P P B
PICO 3 (MenABCWY as option for MenB) Q P P
Combination of all 3 PICOs P P P
58Draft Proposal to the ACIP
▪Forindividuals aged 10 years or older, Pfizer’s MenABCWY vaccine may be used as an alternative to
MenACWY and MenB vaccines only when both vaccines are indicated to be given at the same time.
This proposal applies to healthy individuals (routine schedule) and those at increased risk for
meningococcal disease.
59Draft Proposal to the ACIP
▪Forindividuals aged 10 years or older, Pfizer’s MenABCWY vaccine may be used as an alternative to
MenACWY and MenB vaccines only when both vaccines are indicated to be given at the same time.
This proposal applies to healthy individuals (routine schedule) and those at increased risk for
meningococcal disease.
–Remarks:
•This proposal is not intended to supersede or negate the shared clinical decision -making
recommendation for MenB.
•The licensed MenB vaccines are not interchangeable, so use of the Pfizer pentavalent vaccine for
the first MenB dose would require subsequent doses to be a Pfizer MenB -FHbp vaccine or
pentavalent Pfizer MenB -FHbp -containing vaccine.
•The minimum interval for the Pfizer pentavalent vaccine is 6 months. Individuals at increased risk of
meningococcal disease who are recommended to receive additional doses of MenACWY and MenB
less than 6 months after a dose of pentavalent meningococcal vaccine should instead receive
separate MenACWY and MenB -FHbp vaccines.
•The workgroup will review extended interval data when available in anticipation that this may
provide support for updated schedules that provide protection for all 5 serogroups.
Strengths and Weaknesses of Q -P-B (PICO 1)
▪ Strengths
– Reduces doses from 4 to 3
– Cost savings
• ~$95 per person for the routine schedule
• Q-Q-B-B (~$746) vs. Q -P-B (~$651)
– CostperQALY saved less than standard of care
– Relatively straightforward proposal
▪ Weaknesses
– Does not match dosing used in clinical trials (2 doses at 0,6m)
– Would require stocking 3 vaccine types (MenACWY , MenABCWY , MenB), which might not be acceptable to some clinicians
– Some clinics might not have funds available to stock multiple formulations, which could increase inequities
– Could be challenging for some recipients to complete MenB series if provider does not carry MenB -FHbp
– If ACIP does not recommend second dose of MenABCWY , insurance companies might not cover it in lieu of MenB
– Potentially could increases risk of provider vaccine administration error1,2
601CDC. Timing and Spacing of Immunobiologics : General Best Practice Guidelines for Immunization. ACIP Timing and Spacing Guidelines for Immunization | CDC .
2Hall E, Odafe S, Madden J, Schillie S. Qualitative Conceptual Content Analysis of COVID -19 Vaccine Administration Error Inquiries. Vaccines . 2023; 11(2):254.
Strengths and Weaknesses of Q -P-P (PICO 3)
▪ Strengths
–Reduces doses from 4 to 3
–Small cost savings
•~$27 per person for the routine schedule
•Q-Q-B-B (~$746) vs. Q -P-P (~$719)
–Relatively straightforward proposal
–Potentially allows stocking two vaccines for most patients
–Matches dosing used in clinical trials (2 doses at 0,6m)
▪ Weaknesses
–Persons needing 3 doses of MenB would still need Trumenba because of 6m minimum interval
–Less cost savings than Q -P-B
–Higher cost perQALY saved compared to standard of care
–Concerns from WG that this option could lead to MenB vaccine being discontinued (but need for
Trumenba for persons at increased risk might reduce likelihood)
61
Comparison of Q -P-B and Q -P-P
Criteria Q-P-B Q-P-P
Number of doses saved 1 1
Cost savings per person compared to standard of care $95 $27
Less cost perQALY saved than standard of care Yes No
Number of vaccine types required for the routine schedule 3 2
Number of vaccines types required for the increased -risk schedule 3 3
Matches dosing used in clinical trials No Yes
Unnecessary doses of one or more serogroups No Yes
62
63Acknowledgments
▪ ACIP Members on the WG
–Kathy Poehling (Chair)
–Lynn Bahta
–Jamie Loehr
▪ Ex Officio WG Members
–Margaret Bash (FDA)
–Mark Connelly (FDA)
–Francisco Leyva (NIH)
▪ WG Liaisons and Consultants
–Amra Resic (AAFP)
–Samir Shah (AAP)
–Sharon McMullen (ACHA)
–Cacky Tate (AIM)
–Paul Cieslak (CSTE)
–Kathy Hsu (IDSA)
–Joseline Zafack (NACI)
–Jeff Goad (NFID)
–Jessica Cataldi (PIDS)
–Amy Middleman (SAHM)
–David Stephens (Emory)▪ CDC Contributors
–Jenn Collins (DBD/NCIRD)
–Lucy McNamara (DBD/NCIRD)
–LeAnne Fox (DBD/NCIRD)
–Susan Hariri (DBD/NCIRD)
–Amy Rubis (DBD/NCIRD)
–Noele Nelson (DBD/NCIRD)
–Alison Albert (DBD/NCIRD)
–Angela Jiles (DBD/NCIRD)
–Jonathan Duffy (DHQP/NCEZID)
–Tanya Myers (DHQP/NCEZID)
–Ismael Ortega -Sanchez (DVD/NCIRD)
–Liz Velazquez (ISD/NCIRD)
–Jessica MacNeil (ACIP Secretariat)
▪ GRADE/EtR Support
–Doug Campos -Outcalt (Arizona)
–Rebecca Morgan (Case Western Reserve)
Backup Slides
Evidence Retrieval
▪Systematic review of studies in any language from Medline, Embase,
Global Health, CINAHL, Cochrane, Scopus, and clinicaltrials.gov databases
using search string:
–meningococcal pentavalent, pentavalent meningococcal, Pfizer pentavalent meningococcal,
MenABCWY , Pfizer MenABCWY , pentavalent MenABCWY ,
ABCWY , MenABCWY meningococcal, Neisseria meningitidis group A, B, C, W, and Y , Neisseria
meningitidis A, B, C, W, and Y , Neisseria meningitidis pentavalent, bivalent RLP2086 -containing
pentavalent, NCT03135834, B1971057, NCT04440163, C3511001, NCT04440176, C3511004, and
“vaccin *”
▪Efforts made to obtain unpublished or other relevant data
▪Included results that presented primary data on Pfizer’s MenABCWY
vaccine
65
Evidence Screening Steps
Materials shared by
Pfizer (n=5)References identified
in database search
(n=43)
Title and abstract
screening (n=43)
Full-text article or
public data screening
(n=14)
Records excluded
(n=10)Records excluded
(n=29)
Data sources included
in GRADE analysis: 9
(documenting results
of 3 clinical trials)66
GRADE Certainty of Evidence Categories
Evidence
TypeStudy Design
HighRandomized controlled trials (RCTs) or overwhelming evidence
from observational studies
ModerateRCTs with important limitations, or exceptionally strong
evidence from observational studies
Low Observational studies, or RCTs with notable limitations
Very lowClinical experience and observations, observational studies with
important limitations, or RCTs with several major limitations
67
Short -Term Immunity Key Findings (Table 3a)
Author,
Pub yearAgeSerogroup
(Test strain)n/N
ABCWYn/N
comparisonIntervention
vaccineComparator
vaccine% (95% CI) for
intervention% (95% CI) for
comparator Effect estimate —
RR (95% CI)
Seroresponse based on hSBA titer11 month after 1 intervention dose
Pfizer CT
(NCT04440163),
202010–25 years;
ACWY naïveA 484/499 242/254
MenABCWY (1
dose)MenACWY -
CRM (1 dose)
+ MenB -
FHbp (1
dose) 97.0% (95.1 –98.3) 95.3% (91.9 –97.5) 1.02 (0.99 –1.05)
C 315/501 132/252 62.9% (58.5 –67.1) 52.4% (46.0 –58.7) 1.2 (1.05 –1.37)
W 390/492 178/244 79.3% (75.4 –82.8) 73.0% (66.9 –78.4) 1.09 (0.99 –1.19)
Y 405/494 175/248 82.0% (78.3 –85.3) 70.6% (64.5 –76.2) 1.16 (1.06 –1.27)
10–25 years;
ACWY primedA 416/439 220/227 94.8% (92.2 –96.7) 96.9% (93.7 –98.8) 0.98 (0.95 –1.01)
C 410/439 214/226 93.4% (90.7 –95.5) 94.7% (90.9 –97.2) 0.99 (0.95 –1.03)
W 417/428 214/222 97.4% (95.4 –98.7) 96.4% (93.0 –98.4) 1.01 (0.98 –1.04)
Y 417/442 209/223 94.3% (91.8 –96.3) 93.7% (89.7 –96.5) 1.01 (0.97 –1.05)
Seroresponse based on hSBA titer 1 month after 2 intervention doses
Pfizer CT
(NCT0444016
3), 202010–25 years;
B naïve2B (A22) 646/778 313/396
MenABCWY
(2 doses 6
months
apart)MenACW
Y-CRM (1
dose) +
MenB -
FHbp (2
doses 6
months
apart)83% (80.2 –85.6) 79.0% (74.7 –82.9) 1.05 (0.99 –1.12)
B (A56) 774/807 378/400 95.9% (94.3 –97.2) 94.5% (91.8 –96.5) 1.01 (0.99 –1.04)
B (B24) 567/833 239/418 68.1% (64.8 –71.2) 57.2% (52.3 –62.0) 1.19 (1.08 –1.31)
B (B44) 731/845 332/419 86.5% (84.0 –88.7) 79.2% (75.0 –83.0) 1.09 (1.03 –1.15)
B (composite) 591/755 263/419 78.3% (75.2 –81.2) 68.7% (63.8 –73.3) 1.25 (1.15 –1.35)
681hSBA = serum bactericidal assay using human complement. For participants with a baseline hSBA titer <1:4, seroresponse is defined as a titer ≥1:16. For those with a baseline hSBA titer ≥1:4 and
<1:8 (<1:16 for A22), seroresponse is a titer ≥4 times the 1:8 (1:16 for A22). For those with a baseline hSBA titer ≥1:8 (≥1:16 for A22), seroresponse is a titer ≥4 times the baseline titer.
2Serogroup B primed not assessed.
Persistent Immunity Key Findings (Table 3b)
Author, pub year AgeSerogroup
(Test strain)n/N
MenABCWYn/N
comparisonIntervention
vaccine Comparator
vaccine% (95% CI) for
intervention% (95% CI) for
comparator Effect estimate —
RR (95% CI)
Seroprotection (defined as hSBA titer ≥1:8 for all but A22 which is ≥1:16) at 48 months (54 months for MenACWY -CRM) after last dose
Pfizer CT
(NCT03135834)
201710–25 years;
ACWY naïveA 58/71 26/41
MenABCWY (2
doses 6 months
apart)MenACWY -
CRM (1 dose) +
MenB -FHbp (2
doses 6 months
apart) 81.7% (70.7 –89.9) 63.4% (46.9 –77.9) 1.29 (1.00 –1.67)
C 44/71 16/42 62.0% (49.7 –73.2) 38.1 % (23.6 –54.4) 1.63 (1.06 –2.49)
W 64/70 29/41 91.4% (82.3 –96.8) 70.7% (54.5 –83.9) 1.29 (1.05 –1.59)
Y 71/71 40/42 100.0% (94.9 –100.0) 95.2% (83.8 –99.4) 1.05 (0.98 –1.12)
10–25 years;
B naïveB (A22) 39/139 30/94 28.1% (20.8 –36.3) 31.9% (22.7 –42.3) 0.88 (0.59 –1.31)
B (A56) 50/145 29/98 34.5% (26.8 –42.8) 29.6% (20.8 –39.7) 1.17 (0.80 –1.70)
B (B24) 53/145 26/98 36.6% (28.7 –44.9) 26.5% (18.1 –36.4) 1.38 (0.93 –2.04)
B (B44) 27/148 16/99 18.2% (12.4 –25.4) 16.2% (9.5 –24.9) 1.13 (0.64 –1.98)
10–25 years;
ACWY
primedA 40/40 23/23 100.0% (91.2 –100.0) 100.0% (85.2 –100.0) 1.00 (1.00 –1.00)
C 75/76 52/58 98.7% (92.9 –100.0) 89.7% (78.8 –96.1) 1.10 (1.01 –1.21)
W 40/40 21/23 100.0% (91.2 –100.0) 91.3% (72.0 –98.9) 1.10 (0.97 –1.24)
Y 40/40 22/22 100.0% (91.2 –100.0) 100.0% (84.6 –100.0) 1.00 (1.00 –1.00)
Persistent Immunity Key Findings, Continued
Author, pub year Age Serogroupn/N
MenABCWYn/N
comparisonIntervention
vaccine Comparator
vaccine% (95% CI) for
intervention% (95% CI) for
comparator Effect estimate —RR (95% CI)
Seroprotection (defined as hSBA titer ≥1:8) at 13 months (12 months for MenACWY -CRM) after last dose
Pfizer CT
(NCT04440176),
2020, and Pfizer CT
(NCT03135834), 201711–14 years for
NCT04440176
and 10 –25 years
for
NCT03135834;
both groups
ACWY naiveA 102/126 42/59
1 dose of
MenABCWY1 dose of
MenACWY -CRM81.0% (73.0 –87.4) 71.2% (57.9 –82.2) 1.14 (0.95 –1.37)
C 92/127 32/62 72.4% (63.8 –80.0) 51.6% (38.6 –64.5) 1.40 (1.08 –1.83)
W 125/128 52/62 97.7% (93.3 –99.5) 83.9% (72.3 –92.0) 1.16 (1.04 –1.30)
Y 122/126 61/62 96.8% (92.1 –99.1)98.4% (91.3 –
100.0)0.98 (0.94 –1.03)
70
Serious Adverse Event Findings
1Nine SAEs occurred in 7 patients: Salmonella gastroenteritis (1 patient), depression (1 patient), anxiety (1 patient), suicide attempt (1 patient),
postural orthostatic tachycardia syndrome (1 patient), dyspnea (1 patient), head injury due to motor vehicle accident (1 pati ent), traumatic spinal
cord injury (1 patient), depression with suicidal ideation (1 patient). None of the SAEs were deemed related to the vaccine by the study
investigators.
2Eight SAEs occurred in 6 patients: cyst (1 patient), tendon injury (1 patient), dyskinesia (1 patient), migraine with aura (1 patient), aggression (1
patient), conversion disorder (1 patient), suicidal ideation (2 patients). None of the SAEs were deemed related to the vaccine by the study
investigators. 711
2
Non -Serious Adverse Event Findings
72▪Additional findings related to non -serious adverse events
– NCT04440163: Attention -deficit/hyperactivity disorder (ADHD) was reported by 6 participants in the MenABCWY group
as newly diagnosed chronic medical conditions (NDCMC). Five had an onset of ADHD -related symptoms that occurred
prior to study enrollment and the remaining participant had a history of one or more conditions prior to enrollment
that commonly co -occur with ADHD, including anxiety, depression, and substance use. Overall, none of the NDCMCs
reported were considered related to vaccine by the investigators.
– No other non-serious adverse events that we are aware of were disproportionately overrepresented in the
MenABCWY group from any of the trials.
Nimenrix Background
▪Nimenrix is not approved in the United States, but has been available in
other parts of the world for about a decade
▪The next few slides provide some background on the vaccine’s safety,
immunogenicity, and potential interference with other routinely
administered vaccines
73
Nimenrix Safety
▪First licensed in the European Union in April 2012
▪Currently licensed in more than 80 countries worldwide
▪More than 20 thousand people participated in Nimenrix clinical trials
▪Over a decade of post -marketing safety data available
–More than 30 million doses given worldwide
–Safety consistent between CTs and post -marketing experience
–Most common adverse events —fever, headache, injection site pain, nausea/vomiting,
fatigue
–Serious adverse events rare relative to doses given
–Safety also consistent with other licensed meningococcal vaccines
1Serra et al. Clinical trial and postmarketing safety experience with MenACWY -TT, a meningococcal group A, C, W, and Y tetanus c onjugate vaccine.
Vaccine . 2022; 40:7014 –7021. 74
Nimenrix Safety, Continued
▪One clinical trial on MenACWY -TT and asplenia1
–Phase III, non -randomized study
–1 to 17 year olds with impaired splenic activity with age -matched healthy
controls
▪Results
–Both study groups had high and comparable hSBA vaccine response rates
across serogroups
•First dose: 55.6 –77.1% vs. 60.6 –76.3%
•Second dose: 73.0 –100% vs. 73.0 –85.3%
–SAEs were comparable (4/43 vs. 1/43) and none were deemed vaccine related
•Cystitis due to Escherichia coli , pneumococcal bacteremia, salmonellosis, and sickle -
cell anemia with crisis
1Klein et al. Immunogenicity and safety of the quadrivalent meningococcal ACWY -tetanus toxoid conjugate vaccine (MenACWY -TT) in
splenectomized orhyposplenic children and adolescents: Results of a phase III, open, non -randomized study. Vaccine . 2018. 36;2356 –2363. 75
Nimenrix Persistence Compared to Menactra —5 Years After
Primary Vaccination in Young Adults Aged 11 –25 Years1
1 Pfizer. Nimenrix Product Label. ShowLabeling.aspx (pfizer.com) . 050100150200250
A C W YGMT
SerogroupNimenrix
Menactra
76
Nimenrix Persistence Compared to MenQuadfi —3 Years After
Primary Vaccination in Children Aged 4 –5 Years1
1 Sanofi Pasteur. Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine Administered as a Booster Dose in Children
Vaccinated 3 Years Earlier as Toddlers. EU Clinical Trials Registry. https://www.clinicaltrialsregister.eu/ctr -search/trial/2017 -001993 -40/results . 020406080100120
A C W YGMT
SerogroupNimenrix
MenQuadfi
77
Overall Certainty of Evidence —PICO 1 (Table 5)
Outcome ImportanceIncluded in
Evidence ProfileCertainty for
Healthy
IndividualsCertainty for
Individuals at
Increased Risk
Meningococcal disease caused by
serogroups A, B, C, W, and YCritical No – –
Short -term immunity Critical Yes Moderate Low
Persistent immunity Important Yes Low Low
Interference with other recommended
vaccines administered concurrentlyImportant No – –
Serious adverse events Critical Yes Low Very low
Non -serious adverse events Important Yes Low Very low
78
Overall Certainty of Evidence —PICO 2 (Table 5)
Outcome ImportanceIncluded in
Evidence ProfileCertainty for
Healthy
IndividualsCertainty for
Individuals at
Increased Risk
Meningococcal disease caused by
serogroups A, B, C, W, and YCritical No – –
Short -term immunity Critical Yes Moderate Low
Persistent immunity Important Yes Low Low
Interference with other recommended
vaccines administered concurrentlyImportant No – –
Serious adverse events Critical Yes Low Very low
Non -serious adverse events Important Yes Low Very low
79
Overall Certainty of Evidence —PICO 3 (Table 5)
Outcome ImportanceIncluded in
Evidence ProfileCertainty for
Healthy
IndividualsCertainty for
Individuals at
Increased Risk
Meningococcal disease caused by
serogroups A, B, C, W, and YCritical No – –
Short -term immunity Critical Yes Moderate Low
Persistent immunity Important Yes Moderate Low
Interference with other recommended
vaccines administered concurrentlyImportant No – –
Serious adverse events Critical Yes Low Very low
Non -serious adverse events Important Yes Low Very low
80
Equity Considerations
HISPANIC NON -HISPANIC NON -HISPANIC NON -HISPANIC
WHITE ONLY BLACK ONLY OTHER +
MULTIPLE
RACE
% 1+ dose MenB 31.83 30.88 39.67 24.73Among 17yos in NIS -Teen 2021:
81
Equity Considerations, Continued
82
83Equity Considerations, Continued
▪Potential equity issues exist involving meningococcal vaccination more generally1
–“Among adolescents aged 17 years, coverage with ≥2 MenACWY doses was 11.8 percentage
points lower for those living in non -MSAs than for those in MSA principal cities. Disparities
between non -MSAs and MSA principal cities were statistically significant for adolescents living at
or above the poverty level, but not for those living below the poverty level.”
–“Hispanic or Latino (Hispanic) adolescents had lower coverage with ≥2 MenACWY doses (−10.8
percentage points).”
–“Adolescents who were uninsured had lower coverage with ≥1 MenACWY dose.”
1 Pingali et al. National Vaccination Coverage Among Adolescents Aged 13 –17 Years —National Immunization Survey -Teen, United States, 2021.
MMWR . 2022. 71; 1101 –1108.
84Demographic Information for NCT04440163
85Routine and Increased Risk Vaccine Schedules for ≥10 Years Old
▪Routine
–One MenACWY dose at 11 –12 years and a booster at 16 years
–Two MenB doses at 16 –18 years
▪Increased risk, MenACWY (vaccines are interchangeable)
–Recommended for certain medical conditions (asplenia, complement deficiency, complement inhibitor use, and HIV infection),
some microbiologists, exposure during an outbreak, travel to hyperendemic areas, first -year college students, and military
recruits
–2 doses ≥8 weeks apart for primary vaccination (only 1 dose for microbiologists, travelers, military) and single booster dose
every 5 years thereafter for as long as person remains at increased risk
–Only 1 dose during outbreaks if ≥5 years since MenACWY primary vaccination
–Only 1 dose for first year college students within 5 years before starting college
▪Increased risk, MenB (vaccines are not interchangeable)
–Recommended for certain medical conditions (asplenia, complement deficiency, and complement inhibitor use), some
microbiologists, and exposure during an outbreak
–Bexsero: 2 doses ≥1 month apart followed by single dose 1 year later and every 2 –3 years thereafter for as long as person
remains at increased risk
–Trumenba: 3 doses at 0, 1 –2, and 6 months followed by single dose 1 year later and every 2 –3 years thereafter for period of
increased risk
–Only 1 dose during outbreaks if ≥1 year after MenB primary series