Document text
Introduction to MenB -4C (Bexsero) Interval and Dosing
Label Change
Sarah F. Schillie, MD, MPH, MBA
Advisory Committee on Immunization Practices
October 24, 2024National Center for Immunization & Respiratory Diseases
1
2MenB -4C (Bexsero) Interval Changes
Initially licensed by FDA under an accelerated approval
process
New immunogenicity data support changes to dosing schedule
–No safety concerns
Full FDA approval: August 19, 2024
New dosing schedule aligned with MenB- FHbp
(Trumenba)
https://www.fda.gov/media/90996/download?attachment
https://wayback.archive -it.org/7993/20190423064853/https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProduct s/UCM431447.pdf
3Previous Recommendations (Consistent with Label)
MenB -4C (Bexsero): Previous MenB -FHbp (Trumenba ): Existing
Adolescents:
2-dose series (0, ≥1 month)Adolescents: 2-dose series (0, 6 month)
If dose 2 is administered earlier than 6 months,
administer 3
rd dose at least 4 months after dose 2
Persistent complement component deficiencies,
those with complement inhibitor use, functional or
anatomic asplenia, microbiologists routinely
exposed to Neisseria meningitidis , or persons
affected by an outbreak of serogroup B meningococcal disease:
2-dose series (0, ≥1 month)Persistent complement component deficiencies,
those with complement inhibitor use, functional or
anatomic asplenia, microbiologists routinely
exposed to Neisseria meningitidis , or persons
affected by an outbreak of serogroup B meningococcal disease:
3-dose series (0, 1 –2, 6 months)
3
4New MenB- 4C (Bexsero) Label
Two-dose schedule: Administer a dose (0.5 mL) at 0 and 6 months. If the
second dose is administered earlier than 6 months after the first dose, a
third dose should be administered at least 4 months after the second dose.
Three -dose schedule: Administer a dose (0.5 mL) at 0, 1 –2, and 6
months.
The choice of dosing schedule may depend on the risk of exposure and
the individual’s susceptibility to meningococcal serogroup B disease.
5Proposed ACIP Recommendations
Given the recent MenB- 4C (Bexsero) label change, ACIP will
vote for updated recommendations
Proposed recommendations will achieve alignment between
ACIP recommendations for MenB- 4C (Bexsero) and:
–FDA label
–ACIP MenB -FHbp (Trumenba ) recommendations
Evidence to Recommendations
Framework (Abridged) for
MenB -4C (Bexsero) Interval and
Dosing Change
PICO Questions
PICO 1:
Among persons aged 16 –23 years recommended for MenB vaccination based on
shared clinical decision -making, should MenB -4C be administered on a 0, 6 month
dosing interval, vs. a 0, ≥1 month dosing interval, for the prevention of invasive
meningococcal disease?
PICO 2:
Among persons with persistent complement component deficiencies, those with
complement inhibitor use, functional or anatomic asplenia, microbiologists routinely exposed to Neisseria meningitidis, or persons affected by an outbreak of serogroup B meningococcal disease , should MenB -4C be administered on a 0, 1 –2, 6 month
schedule, vs. a 0, ≥1 month schedule, for the prevention of invasive meningococcal disease?
7
PICO Questions
PICO 1:
Among persons aged 16 –23 years recommended for MenB vaccination based on
shared clinical decision -making, should MenB -4C be administered on a 0, 6 month
dosing interval, vs. a 0, ≥1 month dosing interval, for the prevention of invasive
meningococcal disease? ‘Yes‘ aligns with existing MenB -FHbp (Trumenba )
recommendation
PICO 2:
Among persons with persistent complement component deficiencies, those with
complement inhibitor use, functional or anatomic asplenia, microbiologists routinely exposed to Neisseria meningitidis, or persons affected by an outbreak of serogroup B meningococcal disease , should MenB -4C be administered on a 0, 1 –2, 6 month
schedule, vs. a 0, ≥1 month schedule, for the prevention of invasive meningococcal disease? ‘Yes‘ aligns with existing MenB -FHbp (Trumenba ) recommendation
8
Public health problem
Is invasive meningococcal disease a problem of public health importance?
10Meningococcal Disease
Most often presents as meningitis or bacteremia
Progresses rapidly
10–15% of cases are fatal (even with appropriate antibiotic
therapy)
~20% of survivors experience long -term sequelae
–Cognitive deficits
–Hearing loss
–Limb amputations
00.020.040.060.080.10.12
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023Incidence per 100,000
YearB C Y W Other
Source: NNDSS data with additional serogroup data from Active Bacterial Core surveillance (ABCs) and state health departments
*2023 data are preliminaryTrends in Meningococcal Disease Incidence by
Serogroup – United States, 2006 –2023*
11
12Persons at Increased Risk for Serogroup B Meningococcal Disease
Estimated increased
riskEstimated
population size
Persistent complement component deficiency Up to 10,000 -fold 86,0001
Complement inhibitor use 2,000- fold 3,0002
Anatomic or functional aspleniaCase fatality -rate up
to 40 -70%>80,0003
Microbiologists routinely exposed to N. meningitidis 120- fold 100,0004
Persons exposed during an outbreak Up to 1,400- fold Up to ~33,000
Meningococcal Vaccination: Recommendations of the Advisory Committee on Immunization Practices, United States, 2020 | MMWR (c dc.gov)
1Estimated prevalence in all ages of 0.03% (Densen R. Clin Exp Immunol. 1991) though many may be undiagnosed.
2Preliminary estimate projected from 2017 claims data ( Marketscan and Medicaid)
3Based on estimated 100,000 persons with sickle cell disease (CDC data), minus the ~20,000 children aged <10 years with diseas e (estimated 1,800 -2,000 children identified with sickle cell disease annually
through newborn screening, with 95% survival to age 18 years).
4Bureau of Labor Statistics, 2016. Adjusted to estimate personnel with occupational exposure to N. meningitidis. https://www.b ls.gov/ooh/life -physical- and-social- science/microbiologists.htm#tab -1,
https://www.bls.gov/ooh/healthcare/medical- and-clinical- laboratory -technologists- and-technicians.htm
Meningococcal Disease Outbreaks 2022 -Present
Outbreak Outbreak Period Serogroup Cases (deaths)
Florida MSM December 2021 – February 2023 C 46 (9)
New York PEH February 2022 C 3
Florida College February – March 2022 B 3
Virginia Statewide June 2022 – Present Y 36 (8)*
Iowa Community November 2022 – July 2023 W 12 (2)
Ohio Amish Community December 2023 – January 2024 B 6†
Colorado PEH Jan 2024 – Present Y 6*
Oklahoma Correctional Facility March 2024 – May 2024 C 2 (1)
Kingdom of Saudi Arabia Travel April 2024 – Present W§ 14*
Abbreviation: MSM, men who have sex with men; PEH, people experiencing homelessness
*Ongoing
†5 additional suspect cases
§One additional serogroup C case and one additional nongroupable caseSlide provided by Amy Rubis13
14Is invasive meningococcal disease a problem of public health importance?Public Health Problem
No Probably
noProbably
yesYes VariesDon’t
know
PICO 1:
Healthy adolescents
(0, 6 months)X
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months) X
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?
16Comparators
0, 6 month schedule 0, 2, 6 month schedule
PICO 1 (healthy
adolescents)Dose 2 Dose 2
PICO 2 (persons at increased risk)-- Dose 3 vs. dose 2
CD-6V72_72: Solicited AEs within 7 Days after Vaccination with
MenB- 4C or MenACWYCRM
0%20%40%60%80%100%%Participants*Solicited Local AEs Solicited Systemic AEs
Injection-
site pain†Swelling‡Induration‡Erythema‡Fatigue†Headache†Myalgia†Arthralgia†Nausea† Fever§
Dose 1 2 1 2 1 2 1 2 1 2 1 2 1 2 1 2 1 2 1 2MenB -4C
0,6m
MenB -4C
0,2,6m
MenACWYCRM
(1 dose)
†Severity of symptom‡Size (mm)§Fever ( °C)
Mild – easily tolerated 25–50 38.0– 38.9
Moderate – interferes with normal activity 51–100 39.0– 39.9
Severe – prevents normal activity >100 ≥ 40.0
Generally mild-to-moderate AE were reported following each vaccination
Occurred at similar rates after the 1st, 2nd or 3rd dose of MenB -4C, and were higher than after vaccination with
MenACWYCRM
*Number of participants varies by study vaccination, 823- 835 for MenB -4C and 178 for MenACWY.
AE: Adverse Event
GSK, Data on File 2024N5550603 3 3 3 3 3 3 3 3 3
17
18How substantial are the desirable anticipated effects?Benefits and Harms
Minimal Small Moderate Large VariesDon’t
know
PICO 1:
Healthy adolescents
(0, 6 months)
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months)
18
19How substantial are the desirable anticipated effects?Benefits and Harms
Minimal Small Moderate Large VariesDon’t
know
PICO 1:
Healthy adolescents
(0, 6 months)
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months)
19
20How substantial are the desirable anticipated effects?Benefits and Harms
Minimal Small Moderate Large VariesDon’t
know
PICO 1:
Healthy adolescents
(0, 6 months)
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months)
20
21How substantial are the desirable anticipated effects?Benefits and Harms
Minimal Small Moderate Large VariesDon’t
know
PICO 1:
Healthy adolescents
(0, 6 months)
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months)
21
22How substantial are the desirable anticipated effects?Benefits and Harms
Minimal Small Moderate Large VariesDon’t
know
PICO 1:
Healthy adolescents
(0, 6 months)
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months)
22
23How substantial are the desirable anticipated effects?Benefits and Harms
Minimal Small Moderate Large VariesDon’t
know
PICO 1:
Healthy adolescents
(0, 6 months)X
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months) X X
24How substantial are the undesirable anticipated effects?Benefits and Harms
Minimal Small Moderate Large VariesDon’t
know
PICO 1:
Healthy adolescents
(0, 6 months)X X
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months) X X
25Do the desirable effects outweigh the undesirable effects?Benefits and Harms
Favors
new
dosing
scheduleFavors
previous
dosing
scheduleFavors
bothFavors
neitherVariesDon’t
know
PICO 1:
Healthy adolescents
(0, 6 months)X X
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months) X
Values
- Does the target population feel that the desirable effects are large relative to
the undesirable effects?
- Is there important uncertainty about or variability in how much people value
the main outcome?
MenB Coverage among Adolescents (2023)
≥ 1 dose
among 17 yr olds32.4%
≥ 2 doses
among 17 yr olds12.8%
Pingali C et al. MMWR Morb Mortal Wkly Rep 2024. 27
28Does the target population feel that the desirable effects are large relative to the
undesirable effects? Values
No Probably
noProbably
yesYes VariesDon’t
know
PICO 1:
Healthy adolescents
(0, 6 months)X
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months) X X
29Is there important uncertainty about or variability in how much people value the
main outcome? Values
Important
uncertainty
or
variability Probably
important
uncertainty
or variabilityProbably
not
important
uncertainty
or variabilityNo
important
uncertainty
or variabilityNo known
undesirable
outcomes
PICO 1:
Healthy adolescents
(0, 6 months)X
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months) X
Acceptability
- Is the intervention acceptable to key stakeholders?
31Harmonized Schedules
Harmonized dosing schedules for MenB- 4C (Bexsero) and
MenB- FHbp (Trumenba ) would likely be viewed favorably by
providers
32Extended Dosing Intervals
General Best Practice Guidelines for Immunization. https://www.cdc.gov/vaccines/hcp/acip- recs/general -recs/index.html
Meningococcal Vaccination: Recommendations of the Advisory Committee on Immunization Practices, United States, 2020 | MMWR (cdc. gov) Doses administered at shorter- than -recommended intervals
can result in a sub- optimal immune response
–However, extended intervals prolong the time until one achieves protection
May be challenging for patients needing to complete vaccine
series prior to complement inhibitor therapy initiation
–Persons using complement inhibitors should complete or update vaccination
at least 2 weeks before complement inhibitor initiation unless the risks for delaying treatment outweigh the risks for developing meningococcal disease
33Persons Taking Complement Inhibitors
Among unvaccinated persons for whom complement inhibitor
therapy cannot be delayed, antimicrobial prophylaxis should be
administered alongside meningococcal vaccination and
continued for 2 weeks after vaccine administration
Persons taking complement inhibitors likely remain at
substantially increased risk for meningococcal disease, even if vaccinated and/or taking prophylaxis
Providers could consider continued antimicrobial prophylaxis
for the duration of complement inhibitor treatment
–Clinical judgement indicated
MMWR - Meningococcal Vaccination: Recommendations of the Advisory Committee on Immunization Practices, United States, 2020 (cdc. gov)
34Is the new dosing schedule acceptable to key stakeholders?Acceptability
No Probably
noProbably
yesYes VariesDon’t
know
PICO 1:
Healthy adolescents
(0, 6 months)X
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months) X
Resource use
- Is the intervention a reasonable and efficient allocation of resources?
36Number of Doses
Number of doses remains the same for most healthy
adolescents
–Unless 2nd dose administered earlier than 6 months after
1st dose
Additional dose required for at -risk populations
37Dose Price
Price per Dose
Bexsero (MenB -4C) Trumenba (MenB -FHbp)
Private:
$223.746Private:
$190.26
Public pediatric:$150.026
Public adult:
$128.352Public pediatric:$135.97
Public adult:
$111.90 Harmonization with MenB- FHbp (Trumenba ) dosing
schedule could increase pricing competition
Current CDC Vaccine Price List | VFC Program | CDC
38Is the new dosing schedule a reasonable and efficient allocation of resources?Resource Use
No Probably
noProbably
yesYes VariesDon’t
know
PICO 1:
Healthy adolescents
(0, 6 months)X
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months) X
Equity
- What would be the impact on health equity?
40Schedules that require extended intervals or additional visits
could disproportionately affect populations with lower access to health care
–Unknown to what extent this would occurEquity
41Proportion Completing Series by Age 17 Years:
NIS-TEEN (2022)
%
Non -VFC eligible
MenB -4C (Bexsero) 49.6%
MenB -FHbp (Trumenba ) 35.5%
VFC-eligible
MenB -4C (Bexsero) 51.4%
MenB -FHbp (Trumenba ) 16.2%
42Proportion Completing Series by Age 19 Years:
Commercial Claims (2017- 2023)
%
Continuously -enrolled
MenB -4C (Bexsero) 67%
MenB -FHbp (Trumenba ) 60%
43What would be the impact on health equityEquity
ReducedProbably
reducedProbably
no impactProbably
increasedIncreased VariesDon’t
know
PICO 1:
Healthy adolescents
(0, 6 months)X X
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months) X
Feasibility
- Is the intervention feasible to implement?
45Providers may need to make adjustments to their
practices (e.g., reminder/recall systems)
–Especially for providers who administer MenB vaccine just prior to
college matriculation
Different manufacturers’ MenB vaccine products remain
not interchangeableFeasibility
46Is the new dosing schedule feasible to implement? Feasibility
No Probably
noProbably
yesYes VariesDon’t
know
PICO 1:
Healthy adolescents
(0, 6 months)X
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months) X
Summary
48EtR Domain QuestionPICO 1: WG
DeterminationPICO 2: WG
Determination
Public health
problemIs IMD a problem of public health importance? Yes Yes
Benefits and harmsHow substantial are the desirable anticipated effects? Small Small/moderate
How substantial are the undesirable anticipated effects Minimal/small Minimal/small
Do the desirable anticipated effects outweigh the undesirable effects?Favors new schedule/favors bothFavors new schedule
Values Does the target population feel the desirable effects are large relative to the undesirable effects?Don’t know Don’t know/ probably yes
Is there important variability in how patients value the outcome?Probably not Probably not
Acceptability Is the intervention acceptable to key stakeholders? Probably yes Probably yes
Resource use Is the intervention a reasonable allocation of resources? Probably yes Probably yes
Equity What would be the impact of the intervention on health equity? Probably reduced/probably no impactProbably no impact
Feasibility Is the intervention feasible to implement? Yes Yes
49Balance of Consequences
Undesirable
consequences
clearly outweigh
desirable
consequences in
most settingsUndesirable
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
PICO 1:
Healthy adolescents
(0, 6 months)X X X
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months) X X
50Work Group Interpretation
Yes No
PICO 1:
Healthy adolescents
(0, 6 months)X
PICO 2:
Persons at increased risk
(0, 1– 2, 6 months) XIs there sufficient information to move forward with a recommendation?
51Work Group Interpretation
PICO 1:
Should MenB -4C be administered on a 0, 6 month dosing interval, vs. a 0, ≥1 month
dosing interval, for the prevention of invasive meningococcal disease for persons
aged 16 –23 years recommended for MenB vaccination based on shared clinical
decision -making?
We do not recommend the
interventionWe do recommend the
intervention
X
52Work Group Interpretation
PICO 2:
Should MenB -4C be administered on a 0, 1 –2, 6 month schedule, vs. a 0, ≥1 month
schedule, for the prevention of invasive meningococcal disease among persons with
persistent complement component deficiencies, those with complement inhibitor
use, functional or anatomic asplenia, microbiologists routinely exposed to Neisseria meningitidis, or persons affected by an outbreak of serogroup B meningococcal disease?
We do not recommend the
interventionWe do recommend the
intervention
X
53Proposal Language
ACIP recommends MenB -4C (Bexsero) be administered as a 2 -dose
series at 0 and 6 months when given to healthy adolescents and young
adults aged 16 –23 years based on shared clinical decision -making for the
prevention of serogroup B meningococcal disease
ACIP recommends MenB -4C (Bexsero) be administered as a 3 -dose
series at 0, 1–2, and 6 months when given to persons aged ≥10 years at increased risk for serogroup B meningococcal disease (i.e., persons with
anatomic or functional asplenia, complement component deficiencies, or
complement inhibitor use; microbiologists routinely exposed to N.
meningitidis isolates; and persons at increased risk during an outbreak)
Summary and Work Group Considerations
Regarding MenB -4C (Bexsero)
Interval and Dosing Change
55Summary
Proposed recommendations will align with updated FDA label for MenB -4C
(Bexsero)
–Harmonized with existing recommendations for MenB -FHbp (Trumenba )
Pros:
•New dosing schedules associated with increased immunogenicity compared to
previous schedule
•Harmonization between MenB -4C (Bexsero) and MenB -FHbp (Trumenba ) dosing
intervals and schedules likely to be viewed favorably by providers (although vaccines from different manufacturers remain not interchangeable)
Cons:
•Longer interval between doses increases the time to achieve vaccine- induced
protection and delays series completion
•Persons receiving complement inhibitor therapy may need prolonged antimicrobial prophylaxis due to extended time for vaccine series completion
56Proposed MenB -4C (Bexsero) Recommendations
Healthy adolescents and young adults (based on shared clinical decision-
making):
–2-dose series at 0 and 6 months
Persons aged ≥10 years at increased risk for serogroup B meningococcal
disease (i.e., persons with anatomic or functional asplenia, complement
component deficiencies, or complement inhibitor use; microbiologists routinely exposed to N. meningitidis isolates; and persons at increased risk during an
outbreak):
–3-dose series at 0, 1 –2, and 6 months
57Proposal Language
ACIP recommends MenB -4C (Bexsero) be administered as a 2 -dose
series at 0 and 6 months when given to healthy adolescents and young
adults aged 16 –23 years based on shared clinical decision -making for the
prevention of serogroup B meningococcal disease
ACIP recommends MenB -4C (Bexsero) be administered as a 3 -dose
series at 0, 1–2, and 6 months when given to persons aged ≥10 years at increased risk for serogroup B meningococcal disease (i.e., persons with
anatomic or functional asplenia, complement component deficiencies, or
complement inhibitor use; microbiologists routinely exposed to N.
meningitidis isolates; and persons at increased risk during an outbreak)
58Proposed CDC Clinical Considerations
No recommendation to recall persons previously
vaccinated at 0, ≥1 month
–Healthy adolescents
–Persons at increased risk
Persons should continue with booster vaccination
as previously recommended
59Proposed CDC Clinical Considerations, cont.
The 3 -dose series (doses administered at 0, 1– 2, 6
months) may be used to optimize rapid protection for
those who initiate the vaccine series less than 6 months
prior to period of increased risk
–e.g., when series initiation occurs within 6 months of college
matriculation
Would apply to MenB -4C (Bexsero) and MenB -FHbp
(Trumenba )
60CDC Clinical Considerations
(currently recommended for MenB -FHbp [Trumenba ])
When administering the 2 -dose series (e.g., for healthy adolescents):
–If the second dose is administered <6 months after the first dose, a third dose should
be administered ≥4 months after the second dose (as per label)
–A second dose administered ≥6 months following the first dose is valid and does not need to be repeated
When administering the 3 -dose series (e.g., for persons at increased risk):
–A third dose is not needed if the second dose was administered ≥6 months after the
first dose
–If the third dose is administered <4 months after the second dose and <6 months
after the first dose, the dose should be repeated ≥ 4 months after the last dose
61Clinical Considerations, cont. (Unchanged)
MenB vaccines from different manufacturers are not interchangeable
–All doses in a series, as well as booster doses, should be from the same manufacturer.
–If doses from both manufacturers have been administered to the same patient, the
patient should receive a complete series of either manufacturers’ product without counting doses of the other manufacturer as valid.
MenB -4C (Bexsero) may be administered simultaneously with other
vaccines
–MenB vaccine should be administered in a separate limb from other vaccines
administered on the same clinic day, if feasible.
Contraindications: Severe allergy to prior dose or component of vaccine
Precautions: Pregnancy, moderate or severe acute illness
62Acknowledgements
Lucy McNamara
Amy Rubis
Gabrielle Cooper
Cheryl Isenhour
LeAnne Fox
Susan Hariri
Noele Nelson
Thank you!
63For more information, contact CDC
1-800- CDC- INFO (232- 4636)
TTY: 1 -888- 232- 6348 cdc.gov
Follow us on X (Twitter) @CDCgov & @CDCEnvironment
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position o f
the U. S. Centers for Disease Control and Prevention.