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Meningococcal
(Groups A, C, Y,
andW) Conjugate
Vaccine ( MenQuadfi®)
Extension of use to include
infants from 6 weeks of age
Agenda
Public health
burden of invasive
meningococcal
diseaseRationale for clinical
developmentClinical data from
infant studiesSummary
2
Public health burden of meningococcal disease
•Meningococcal disease remains a major global health challenge because it can strike quickly
and with devastating effect, taking a life in < 24 hours 1,2
•Case-fatality rate is ~10% to 15% even with appropriate treatment2
•~1 in 5 survivors suffer permanent sequelae3,4
•Since introduction of the first MenACWY conjugate vaccine in 2005, MenACWY -D, IMD
caused by serogroups C, W, and Y has declined by > 90% among adolescents and young adults5
•Infants continue to have the highest incidence of IMD, so we would like to share
information about the performance of Sanofi's MenACYW -TT in this population
1. Thompson MJ, et al. Lancet . 2006;367(9508):397- 403. 2. WHO. https://www.who.int/en/news -room/fact -sheets/detail/meningococcal -meningitis [accessed March 2020]. 3. CDC.
MMWR . 2013;62(RR -2):1-22. 4. Rosenstein NE, et al. N Engl J Med. 2001;344(18):1378- 1388. 5. MacNeil JR, et al . Clin Infect Dis 2018; 66:1276– 81.
Limb amputation
Deafness
Brain damage3
What is MenQuadfi (MenACYW -TT)?
•A quadrivalent meningococcal conjugate vaccine to help prevent invasive meningococcal disease
caused by serogroups A, C, W, and Y
•FDA approved on 23 April 2020 for use in persons 2 years of age and older
•Developed with the ambition of being:
•Used across a broad age range
oStudies to support expansion of age indication to include infants as young as 6 weeks of age are
completed
•Incorporated in various immunization schedules that exist worldwide
•Conjugated to tetanus toxoid (approximately 55 µg)
•Each 0.5 -mL intramuscular dose contains 10 µg each of the 4 meningococcal
polysaccharides
•Fully liquid solution that does not require reconstitution and supplied in a single -dose vial4
Age at First Dose Primary Vaccination Schedule
Infants aged from 6 weeks 4-dose series at 2, 4, 6 and between 12
and 18 months of age. The first dose may
be given as early as 6 weeks.
Infants aged 6 months through 23 months 2-dose series with the second dose
administered in the second year of life and at least 3 months after the first dose.
Individuals 2 years of age and older A single doseProposed Schedule for Primary Vaccination with MenACYW -TT5
Overview of MenQuadfi
Clinical Development
Toddlers
(12–23 Months)
Infants
(6 Weeks –11 Months)
MET42
Phase III
Schedule: 3+1 (2, 4, 6, 12– 18M)
Control MenACWY -CRM
USA
NCT03537508MET58
Phase III
Schedule: 2+1 (2, 4, 12– 18M)
and 3+1 (2, 4, 6, 12– 18M)
Control MCV4 -TT
Europe*
NCT03547271MET52
Phase III
Schedule: 1+1 (3, 12– 13M)
NI when co -ad MenB and
standard of care vaccines§
(multi -dose)
UK
NCT03632720
MET61
Phase III
Schedule: 1+1 (6M+)
Controls MenACWY -CRM, MenACWY -D
USA
NCT03691610MET41
Phase III
Schedule: 3+1 (2, 4, 6, 12M)
Control MenACWY -CRM
USA
NCT03673462MET33
Phase III
Schedule: 2+1 (2 or 3, 6, 12M)
Control MenACWY -CRM in 3 +1
(2, 4, 6, 12M)
Russia, Mexico
NCT03630705
MEQ00089
Phase III
Schedule: 1+1 (6M+): 6- 7 +12- 13 M
Control: MCV4 -TT
EU
ONGOINGMEQ00065
Phase III
NI / Superiority
Controls MenC -conj and MCV4 -TT
(single -dose)
Denmark, Finland, Germany
NCT03890367
MEQ00086
Interchangeability
Toddlers (12−23M)
Toddlers primed with MenACWY -CRM or MCV4 -TTduring
1Y
Argentina
ONGOINGToddlers
(12–23 Month s)
MET54
Phase II
Control MCV4 -TT
(single dose )
Finland
NCT03205358
MET51
Phase III
Control: MCV4 -TT
(single dose )
Germany, Spain,
Finland, Hungary
NCT02955797
MET57
Phase III
Single dose co -ad* with MMR + varicella, DTaP -IPV-
HB-Hib, or PCV13 (single dose)
No Meninge vaccine control
South Korea, Russia, Mexico, Thailand
NCT03205371MenQuadfi
Clinical
Development
Program in
Infants and
Toddlers
Coadministration study
Booster dose study
MenACWY -TT = MenQuadfi , MenACWY -CRM = Menveo, MenACWY -D = Menactra , MCV4 -TT= Nimenrix (not licensed in US)
-Studies in green font are completed
-Studies in black font are ongoing7
&
MET42
Immunogenicity and Safety
Study of a Quadrivalent
Meningococcal Conjugate
Vaccine (MenACYW -TT) when
Co-administered with Routine
Pediatric Vaccines in Healthy
Infants and Toddlers in the US
and Puerto Rico
Short Study Title Immune Non -inferiority, Safety and Co -
administration study in infants & toddlers
Study PopulationAge group ≥ 42 to ≤ 89 days
Number of
participants2627
Meningococcal -vaccine naïve
Vaccine GroupsGroup 1: MenACYW -TT + Routine pediatric vaccines
Group 2: MenACWY -CRM + Routine pediatric
vaccines
Vaccination ScheduleSingle dose of MenACYW -TT or MenACWY -CRM (2,
4, 6, and 12 months )
Safety follow upImmediate
Unsolicited
Systemic
AEsWithin 30 minutes after each vaccination
Solicited
AEsDay 0 toDay 7 after each vaccination
Unsolicited
AEsD0 to D30 after each vaccination
SAEs
(AESIs and
MAAEs)Visit1 (day of firstvaccination) untiltheendof the
6-month follow -up period after thelastvaccination.MET42: Study design and demographic data9
Baseline CharacteristicsGroup 1
(N=1746)Group 2
(N=881)
Sex: n (%)
Male 918 (52.6) 466 (52.9)
Female 828 (47.4) 415 (47.1)
Sex ratio: Male/Female 1.11 1.12
Age: (Days)
Mean (SD) 65.3 (8.02) 65.3 (7.81)
Min ; Max 42.0 ; 89.0 42.0 ; 89.0
Median 64.0 64.0
Racial origin: n (%)
American Indian or Alaska
Native 11 (0.6) 3 (0.3)
Asian 15 (0.9) 10 (1.1)
Black or African American 204 (11.7) 99 (11.2)
Native Hawaiian or Other Pacific
Islander7 (0.4) 6 (0.7)
White 1428 (81.8) 722 (82.0)
Mixed Origin 44 (2.5) 30 (3.4)
Unknown 19 (1.1) 6 (0.7)
Ethnicity: n (%)
Hispanic or Latino 838 (48.0) 410 (46.5)
Not Hispanic or Latino 897 (51.4) 465 (52.8)
Unknown 3 (0.2) 4 (0.5)
Not reported 8 (0.5) 2 (0.2)
Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers in the
US. ClinicalTrials.gov , Sanofi Pasteur, 15 Oct. 2024, https://clinicaltrials.gov/study/NCT03537508
AESI: Adverse events of special interest, MAAE: Medically attended adverse events.
MET42
Safety
24.126.6 28.4 29.833.2 34.7
13.6 13.619.6 18.927.330.134.433.825.528.6 20.220
9.57.512 14.212.712.911.811.4
8.56.5
66.4
1.11.21.72.12.93.4
0102030405060708090100
Crying abnormal Drowsiness Vomitting Fever Apetite lostGrade 1
Grade 2
Grade 3
Group 1: MenACYW -TT and routine pediatric vaccines; Group 2: MenACWY -CRM and routine pediatric vaccinesMET42: Solicited injection site & systemic reactions within 7 days after
any dose 11
Injection site Reactions
Tenderness was the most frequently reported solicited injection
site reaction. Erythema and swelling were reactions less
frequently experienced. Most solicited injection site reactions were
of Grade 1 or 2 intensity.Irritability was the most frequently reported solicited systemic
reaction, followed by crying abnormal, drowsiness & appetite lost.
Fever (33.4% vs 35.2%) and vomiting were reactions less frequently
experienced. Most solicited systemic reactions were of Grade 1 or 2
intensity
Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers in the
US. ClinicalTrials.gov, Sanofi Pasteur, 15 Oct. 2024, https://clinicaltrials.gov/study/NCT03537508 Systemic Reactions
Irritability Crying abnormal Drowsiness Vomiting Fever34.5 35.332.1 30.9
23.5 21.823.6 23.6
11.7
0.91.29.1 8.7
0.20.5
0.20.4
0102030405060708090100
GROUP 1 GROUP 2 GROUP 1 GROUP 2 GROUP 1 GROUP 2
ERYTHEMA SWELLINGGrade 1
Grade 2
Grade 3
Tenderness Erythema SwellingAppetite
lostGroup 1Group 2 Group 2 Group 2 Group 2 Group 2 Group 2 Group 1 Group 1 Group 1 Group 1 Group 1Percentage of participants
Percentage of participants
MET42: Summary of results
Summary of SAEs, AESIs and unsolicited AEs after any vaccine injections
AESI: adverse events of special interest 99 subjects (5.7%) in Group 1 ( MenACYW -TT), 38 subjects (4.4%) in Group 2 ( MenACWY -CRM) reported SAEs during the study
18 subjects reported AESI during the study: 13 subjects (0.8%) in Group 1 ( MenACYW -TT) and 5 (0.6%) subjects in Group 2
(MenACWY -CRM)
There were 2 subjects (both in Group 1- MenACYW -TT) who discontinued due to SAEs ( Infantile spasms, Cardiac arrest )•2 subjects reported SAEs related to study vaccines during the study:
1 instance of febrile seizure in a participant in Group 1 ( MenACYW -TT) with prior history of seizures. The Febrile seizure was
an AESI (13 days after 15 -month dose)
1 subject reported fever post vaccination in Group 2 ( MenACWY -CRM) (8 hours following 2 -month dose)
•All AESIs were nonrelated to the study vaccines, except the one SAE mentioned above
•There was one death reported in the study. It was deemed unrelated to the study vaccine by the investigator and sponsor
Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers in the
US. ClinicalTrials.gov, Sanofi Pasteur, 15 Oct. 2024, https://clinicaltrials.gov/study/NCT03537508 12
MET42
Immunogenicity
95% CI of the single proportion calculated from the exact binomial method.
Group 1a: MenACYW -TT and routine vaccines at 2, 4, 6, and 12 to 15 months of age
Group 2a: MenACWY -CRM at 2, 4, 6, and 12 months of age and routine vaccines at 2, 4, 6, 12, and 15
to 18 months of ageVaccine seroresponse * at day 30 after the booster dose (Group 1 vs Group 2) in Per -protocol Analysis Set
*hSBA vaccine seroresponse for serogroups A, C, Y, and W was defined as:
•For a subject with a pre -vaccination titer < 1:8, the post- vaccination titer had to be ≥ 1:16
•For a subject with a pre -vaccination titer ≥ 1:8, the post- vaccination titer had to be ≥ 4-fold greater than
the pre -vaccination titerMET42 primary endpoint 1Percentage of subjects with vaccine seroresponse MET42: Post booster, MenACYW -TT seroresponse rates were comparable to those
for MenACWY -CRM for serogroups A, Y, W and higher for serogroup C
79.497 96.4 97.6
77.688.292.396.4
0255075100
A C Y WParticipants achieving
seroresponse (%, 95% CI)
Group 1a: MenACYW-TT (N=675) Group 2a: MenACWY-CRM (N=308)14
Primary objective 1 was met: The percentage of subjects who achieved vaccine seroresponse rate post -dose 4 for meningococcal
serogroups A, C, W, and Y in MenACYW -TT (Group 1a) are non -inferior to the corresponding percentages in MenACWY -CRM (Group 2a), as the
lower limit of the 2 -sided 95% confidence interval (CI) of the difference between MenACYW -TT (Group 1a) and MenACWY -CRM (Group 2a) were
higher than -10% for all 4 serogroups
Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers in the
US. ClinicalTrials.gov, Sanofi Pasteur, 15 Oct. 2024, https://clinicaltrials.gov/study/NCT03537508
N: number of subjects in per -protocol analysis set 2, for booster series.
95% CI of the single proportion calculated from the exact binomial method.
Group 1a: MenACYW -TT and routine vaccines at 2, 4, 6, and 12 to 15 months of age
Group 2a: MenACWY -CRM at 2, 4, 6, and 12 months of age and routine vaccines at 2, 4, 6, 12, and 15
to 18 months of age
PPAS, Per -Protocol Analysis SetMET42 primary endpoint 2Percentage of subjects with hSBA titer >= 1:8 ( seroprotection )MET42: Post 3 -dose infant series, MenACYW -TT seroprotection rates were higher
than those for MenACWY -CRM for all 4 serogroups
77.999 98.3 98.6
67.791.2 91.7 92.9
0255075100
A C Y WParticipants achieving
seroprotection (%, 95% CI)
Group 1a: MenACYW-TT (N=928) Group 2a: MenACWY-CRM (N=460)15
Primary objective 2 was met: Non-inferiority of the percentage of subjects with hSBA titers to meningococcal serogroups A, C, Y,
and W ≥ 1:8 following administration of 3 doses of MenACYW -TT compared to 3 doses of MenACWY -CRM when given concomitantly with
pediatric routine vaccines to infants and toddlers at 6 to 7 months of age was demonstrated as the lower limit of the 2 -sided 95% CI of the
difference in hSBA seroprotection rates (antibody titers ≥ 1:8) were > -10% for all 4 serogroups
Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers in the
US. ClinicalTrials.gov, Sanofi Pasteur, 15 Oct. 2024, https://clinicaltrials.gov/study/NCT03537508
10.6
6.6461.3
4.4543.5
9.9757.9
9.0267.156.9678
90.9296
186387
175
1101001000Geometric means of hSBA
titers
Log scaleD0 D30MET42: Geometric mean of hSBA antibody titers pre- and post - 4th dose
Summary of secondary immunogenicity results
D, day;
95% CI calculated using calculation for normal distribution on log10( titer) following by antilog transformation
Group 1a: MenACYW -TT and routine vaccines at 2, 4, 6, and 12 to 15 months of age
Group 2a: MenACWY -CRM at 2, 4, 6, and 12 months of age and routine vaccines at 2, 4, 6, 12, and 15 to 18 months of ageSecondary objective 2: Geometric mean of hSBA antibody titers against meningococcal serogroups A, C, Y and W after 4th dose of
MenACYW -TT were comparable or generally higher for all serogroups for Group 1a vs Group 2a
Summary of geometric means of hSBA titers at D0 before the 4th dose and D30 after the 4th dose - Per-Protocol Analysis Set 3
Serogroup A C Y WGroup 1a Group 1a Group 1a Group 1a Group 2a Group 2a Group 2a Group 2a16
Secondary objective 1 was met: Non-inferiority of immune responses of the routine pediatric vaccines administered concomitantly with
MenACYW -TT as compared with MenACWY -CRM in infants and toddlers 6 weeks old to 18 months of age was demonstrated
Ab, antibody; ELISA, enzyme -linked immunosorbent assay; GMC, geometric mean concentrations; PRP, anti polyribosyl -ribitol phosphate
*Pertussis antigen: PT, FHA, PRN, and FIM; †Polioviruses: type 1, type 2, type 3; ‡Pneumococcal serotypes: 1, 3, 4, 5, 6A, 6B , 7F, 9V, 14, 18C, 19A, 19F, and 23F1st Year,
30 days after the
6-month
vaccinationHepatitis B % ≥10 mIU/mL 10% Yes
PRP % ≥0.15 µg/mL 5% Yes
PRP % ≥ 1.0 µg/mL 10% Yes
Polio† % ≥1:8 5% Yes
Rotavirus % ≥ 3 -fold rise 10% Yes
Rotavirus GMC (G1/G2 ratio) 1.5 Yes
Pertussis* GMC (G1/G2 ratio) 1.5 Yes
Pneumococcal‡ GMC (G1/G2 ratio) 2 YesEvaluation
TimeAntigen EndpointNon-
inferiority
marginNon-
inferiority?
2nd Year,
30 days after the 12-month
vaccinationMeasles % ≥ 255 mIU/mL 10% Yes
Mumps% ≥ 10 mumps Ab
units/mL10% Yes
Rubella % ≥ 10 IU/mL 10% Yes
Varicella % ≥ 5 gpELISA units/mL 10% Yes
Pneumococcal‡ GMC (G1a/G2a ratio) 2 Yes
2nd Year,
30 days after the
15-month
vaccinationPRP % ≥1.0µg/mL 10% Yes
Polio† % ≥1:8 5% Yes
Pertussis* Response rate 10% YesMET42: Results on concomitant administration of pediatric vaccines17
Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers in the
US. ClinicalTrials.gov, Sanofi Pasteur, 15 Oct. 2024, https://clinicaltrials.gov/study/NCT03537508
MenACYW -TT was non -inferior to MenACWY -CRM, based on hSBA vaccine seroresponse after the 4th dose, when the vaccines
were given at 2, 4, 6, and 12 months of age, along with routine pediatric vaccines
MenACYW -TT was non-inferior to MenACWY -CRM, based on seroprotection after the 3rd dose, when the vaccines were given at 2,
4, 6, and 12 months of age along with routine pediatric vaccinesPrimary immunogenicity objectives were met
Non-inferiority of immune responses to routine pediatric vaccines administered concomitantly with MenACYW -TT as compared with
MenACWY -CRM in infants and toddlers 6 weeks old to 18 months of age was demonstrated
Geometric mean of hSBA titers against meningococcal serogroups A, C, Y and W after 3rd dose of MenACYW- TT were comparable or
higher for all serogroups in the MenACYW -TT group vs MenACWY -CRM group
There were no new safety concerns identified
The safety profile and tolerance of MenACYW -TT was comparable to MenACWY -CRM
Safety data from 3211 subjects who received 4 doses of MenACYW -TT (MET41 and MET42) are shown on later slidesSecondary immunogenicity objectives were met
SafetyMET42: Summary of results18
Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers in the
US. ClinicalTrials.gov, Sanofi Pasteur, 15 Oct. 2024, https://clinicaltrials.gov/study/NCT03537508
MET41
Safety of a Quadrivalent
Meningococcal Conjugate
Vaccine ( MenACYW -TT)
Administered Concomitantly
with Routine Pediatric Vaccines
in Healthy Infants and Toddlers
Short Study Title Immune Non -inferiority, Safety and Co -administration
study in infants & toddlers
Study PopulationAge ≥ 42 to ≤ 89 days
Number of
participants2797
Meningococcal -vaccine naïve
Study DesignGroup 1: MenACYW -TT + Routine pediatric vaccines
Group 2: MenACWY -CRM + Routine pediatric vaccines
Vaccination ScheduleSingle dose of MenACYW -TT or MenACWY -CRM (2, 4,
6, and 12 months )
Safety follow upImmediate
Unsolicited
Systemic
AEsWithin 30 minutes after each vaccination
Solicited
AEsDay 0 toDay 7 after each vaccination
Unsolicited
AEsDay 0 untilthenextstudy visit
SAEs (AESIs
and MAAEs)Visit 1 (day of first vaccination) until the end of the 6 -
month follow -up period after the last vaccination.MET41: Phase III study of MenACYW -TT conjugate vaccine
administered to healthy infants and toddlers20
Safety of a Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers (MET41). ClinicalTrials.gov , Sanofi
Pasteur, 14 Dec. 2023, https://clinicaltrials.gov/study/NCT03673462 Baseline CharacteristicsGroup 1
(N=2099)Group 2
(N=362)
Sex: n (%)
Male 1101 (52.5) 362 (51.9)
Female 998 (47.5) 336 (48.1)
Sex ratio: Male/Female 1.10 1.08
Age: (Days)
Mean (SD) 64.7 (6.63) 64.9 (6.77)
Min ; Max 42.0 ; 89.0 42.0 ; 89.0
Median 63.0 63.0
Racial origin: n (%)
American Indian or Alaska
Native 8 (0.4) 0
Asian 28 (1.3) 12 (1.7)
Black or African American 210 (10.0) 67 (9.6)
Native Hawaiian or Other Pacific
Islander10 (0.5) 5 (0.7)
White 1719 (81.9) 580 (83.1)
Mixed Origin 102 (4.9) 31 (4.4)
Unknown 12 (0.6) 0
Ethnicity: n (%)
Hispanic or Latino 566 (27) 197 (28.2)
Not Hispanic or Latino 1526 (72.7) 499 (71.5)
Unknown 0 0
Not reported 7 (0.3) 9 (0.3)
Summary of SAEs, AESIs and unsolicited AEs after any vaccine injections
AESIs, adverse events of special interest; *Brighton Collaboration is a Global Standard for Case Definitions (and Guidelines) for Adverse Events Following Immunization (AEFI) and adverse events of special interest
(AESI). 12 discontinuations occurred due to AEs throughout the study129/2797 (4.6%) subjects reported serious adverse events (SAEs) . None of these SAEs were assessed to be related to the study vaccines.
20/2797 (0.7%) subjects reported 24 AESIs ( febrile or non -febrile seizures ), none related to the study vaccines.
•19/2080 (0.9%) of AESIs occurred in the MenACYW -TT group.
•1/697 (0.1%) of AESIs occurred in the MenACWY -CRM group. •The most common non -serious unsolicited adverse events (AEs) were in the "Infections and Infestations", with respiratory and
gastrointestinal infections being the most frequently reported
•108/2080 (5.2%) of subjects in the MenACYW -TT group reported SAEs.
•21/697 (3%) of subjects in the MenACWY -CRM group reported SAEs. MET41: Summary of results
•Confounding factors were identified in 21/24 (87.5%) of the AESI cases.
•22/24 (92%) of AESI cases did not meet the Brighton Collaboration* case definition criteria for febrile and non -febrile
seizures.
•7 subjects (all in MenACYW -TT) discontinued due to SAEs, including 3 deaths (non- accidental injury to the head, sudden
unexplained death in infancy, found unresponsive)
•None were considered related to the study vaccine or procedure by the investigator and sponsor.21
Safety of a Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers (MET41). ClinicalTrials.gov, Sanofi
Pasteur, 14 Dec. 2023, https://clinicaltrials.gov/study/NCT03673462
MET41 and MET42 pooled safety analysis22
0.52.1 1.25.2
0.3 1.1 0.93.7
0102030405060708090100
Within 7 days after any vaccine
injections (SafAS for full 4-dose)Within 30 days after any vaccine
injections (SafAS for full 4-dose)During 6-month follow-up period
(SafAS for full 4-dose)During the study
(SafAS for full 4-dose)MenACYW-TT + routine pediatric vaccines
(N=3211)MenACWY-CRM + routine pediatric vaccines(N=1327)
1. Safety of a Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Routine Pediatric Vaccines in Health y Infants and Toddlers (MET41). ClinicalTrials.gov,
Sanofi Pasteur, 14 Dec. 2023, https://clinicaltrials.gov/study/NCT03673462 2. Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine When Administered
Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers in the US. ClinicalTrials.gov, Sanofi Pasteur, 15 Oct. 2024, https://clinicaltrials.gov/study/NCT03537508 Participants experiencing at least one SAEPercentage of participants
MET61
Phase III, modified double -blind,
randomized, parallel group,
active -controlled, multicenter
study of Quadrivalent
Meningococcal Conjugate
Vaccine ( MenACYW -TT) in
infants & toddlers from 6
through 23 months of age in the
United States
Short Study Title Immune Non -inferiority, Safety and Co -administration study in infants &
toddlers
Study PopulationAge Infants 6 to 7 months; Toddlers 17 to 19 months
Number of
participants950
Study DesignGroup 1 : MenACYW -TT
conjugate vaccine + routine pediatric vaccines at 6 to 7months of age and 12 to
13months of age
Group 2 : MenACWY -CRM +
routine pediatric vaccines at 6 to 7months of age and 12 to
13months of ageGroup 3 : MenACYW -TT conjugate
vaccine at 17 to 19 months of age and 20 to 23 months of age
Group 4 : MenACWY -D at 17 to 19
months of age and 20 to 23 months of age
Safety follow upImmediate Unsolicited Systemic AEs: 30 minutes post- vaccination.
Solicited AEs: D0 to D7 post- vaccination
Unsolicited AEs: D0 until the next visit
SAEs (AESIs and MAAEs): Visit 1 to 6 -month follow -upMET61: Phase III Study of immunogenicity and safety of a quadrivalent
meningococcal conjugate vaccine administered concomitantly with routine
pediatric vaccines in healthy infants and toddlers
Baseline
CharacteristicsGroup 1+2Group
3+4
Characteristic
(950)n=750 n=200
Sex, n (%)Male
Female398 (53.1) 100 (50.0)
352 (46.9) 100 (50.0)
Age in years,
mean (SD)6.01 (0.570) 17.9 (0.652)
Race, n (%)WhiteAfrican -
AmericanMixed Origin541 (72.1)
138 (18.4)
35 (4.5)166 (83.0)
22 (11.0)
9 (4.5)
Ethnicity, n
(%)
Hispanic or
Latino330 (44.0)66 (33.0)24
Immunogenicity and Safety Study of a Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers.
ClinicalTrials.gov, Sanofi Pasteur, 25 June 2024, https://clinicaltrials.gov/study/NCT03691610
MET61
Safety
MET61: Solicited injection site reactions within 7 days after any dose
Group 1 (G1): MenACYW -TT vaccine + routine pediatric vaccines at 6 to 7 months of age and 12 to 13 months of age
Group 2 (G2): MenACWY -CRM vaccine + routine pediatric vaccines at 6 to 7 months of age and 12 to 13 months of age
Group 3 (G3): MenACYW -TT vaccine at 17 to 19 months of age and 20 to 23 months of age
Group 4 (G4): MenaACWY -D vaccine at 17 to 19 months of age and 20 to 23 months of age26
Immunogenicity and Safety Study of a Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers.
ClinicalTrials.gov, Sanofi Pasteur, 25 June 2024, https://clinicaltrials.gov/study/NCT03691610 Majority of injection site reactions were Grade 1 (erythema and swelling) and Grade 1 & 2 (tenderness)33.130.236.333
029.9 27.831.9
24
02219.624.2
1314
11.711
7
00.81.20
2
00.3
0.91.1
12.5
2.30
1
00
0.6 0
0
00.30.30
0
0102030405060708090100
G1 G2 G3 G4 G1 G2 G3 G4 G1 G2 G3 G4
Erythema SwellingInjection Site Reactions
Grade 1
Grade 2
Grade 3
TendernessPercentage of participants
MET61: Solicited systemic reactions within 7 days after any dose 27
Immunogenicity and Safety Study of a Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers.
ClinicalTrials.gov, Sanofi Pasteur, 25 June 2024, https://clinicaltrials.gov/study/NCT03691610 25.828.724.227
026.4 26.9 26.422
03231.3
23.1 23
015.719.623.1 23
01110.36.71124.2 20.8
20.919
016.611.7 11
9
010.4 11.4
7.74
05.93.57.7 9
04.9 5.56.766.75
3.36
2 1.81.1
32.5 3.2
0
31.71.20 2
0.9 1.2 1.11
0102030405060708090100
Crying abnormal Drowsiness Appetite lost FeverSystemic Reactions
Grade 1
Grade 2
Grade 3
Irritability Crying abnormal Drowsiness Appetite lost FeverG1 G2 G3 G4 G1 G2 G3 G4 G1 G2 G3 G4 G1 G2 G3 G4 G1 G2 G3 G4
Vomiting occurred less frequently, with 11.8%, 10.8%, 7.7%, and 9% reported in groups 1, 2, 3, and 4, respectivelyPercentage of participants
Group 1 (G1): MenACYW -TT vaccine + routine pediatric vaccines at 6 to 7 months of age and 12 to 13 months of age
Group 2 (G2): MenACWY -CRM vaccine + routine pediatric vaccines at 6 to 7 months of age and 12 to 13 months of age
Group 3 (G3): MenACYW -TT vaccine at 17 to 19 months of age and 20 to 23 months of age
Group 4 (G4): MenaACWY -D vaccine at 17 to 19 months of age and 20 to 23 months of age
Summary of safety events after any vaccine injections
AESIs, adverse events of special interest MET61: Summary of results28
Immunogenicity and Safety Study of a Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers.
ClinicalTrials.gov, Sanofi Pasteur, 25 June 2024, https://clinicaltrials.gov/study/NCT03691610 •A total of 6 participants (1.6%) in Group 1 (MenACYW -TT), 12 participants (3.3%) in Group 2 (MenACWY -CRM), 1 participant (1.0%)
in Group 3 (MenACYW -TT), and 4 participants (3.9%) in Group 4 (MenACWY -D) reported SAEs during the study
•One participant (1.0%) in Group 4 ( MenACWY -D) experienced an SAE (febrile convulsions) that was considered related to vaccination.
This was reported as an adverse event of special interest (AESI).
•All other SAEs were evaluated as non -related to vaccination by Investigators and Sponsor•One participant in Group 2 ( MenACWY -CRM) experienced an immediate unsolicited AE (head injury)
•There was 1 SAE (acute myeloid leukemia not related to the study vaccines), leading to study discontinuation in Group 2 ( MenACWY -
CRM)
•One participant (0.3%) in Group 1 (MenACYW -TT), 2 participants (0.6%) in Group 2 (MenACWY -CRM), and 2 participants (1.9%) in
Group 4 (MenACWY -D) reported an AESI during the study. None of these AESI were related to the study vaccines.
•No deaths were reported during the study
MET61
Immunogenicity
MET61: Post booster, MenACYW -TT seroresponse rates were high and
comparable to those for MenACWY -CRM for all 4 serogroups
95% CI of the single proportion calculated from the exact binomial method.
Group 1: MenACYW -TT vaccine + routine pediatric vaccines at 6 to 7 months of age and 12 to 13
months of age
Group 2: MenACWY -CRM + routine pediatric vaccines at 6 to 7 months of age and 12 to 13
months of ageVaccine seroresponse* at day 30 after the booster dose (Group 1 vs Group 2) in Per -protocol Analysis Set
*hSBA vaccine seroresponse for serogroups A, C, Y, and W was defined as: •For a subject with a pre -vaccination titer < 1:8, the post- vaccination titer had to be
≥1:16
•For a subject with a pre -vaccination titer ≥ 1:8, the post- vaccination titer had to be
≥4-fold greater than the pre -vaccination titer89.499.3 98.6 99.3
82.997.6 97.792.9
0255075100
A C Y WParticipants achieving
seroresponse (%, 95% CI)
Group 1: MenACYW-TT (N=180) Group 2: MenACWY-CRM (N=163)MET 61 primary endpoint 130
Primary objective 1 was met: Post second vaccination at 12 to 13 months of age, non -inferiority of the group 1 vs. group 2 showed the lower
limit of the 95% confidence interval (CI) of the difference in hSBA seroresponse for meningococcal serogroups A, C, W, and Y was above - 10%
Immunogenicity and Safety Study of a Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers.
ClinicalTrials.gov, Sanofi Pasteur, 25 June 2024, https://clinicaltrials.gov/study/NCT03691610 Percentage of subjects with vaccine seroresponse
Seroprotection : hSBA antibody titers ≥ 1:8
N: number of subjects in per -protocol analysis set 2, for booster series.
95% CI of the single proportion calculated from the exact binomial method.
Group 1: MenACYW - TT vaccine + routine pediatric vaccines at 6 to 7 months of age and 12 to 13 months of age
Group 2: MenACWY -CRM + routine pediatric vaccines at 6 to 7 months of age and 12 to 13 months of age
PPAS, Per -Protocol Analysis SetPercentage of subjects with seroprotection
95.3100 100 1009398.1 97.5 95.6
0255075100
A C Y WParticipants achieving
seroprotection (%, 95% CI)
Group 1: MenACYW-TT (N=180) Group 2: MenACWY-CRM (N=163)MET 61 secondary endpoint 131
Immunogenicity and Safety Study of a Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers.
ClinicalTrials.gov, Sanofi Pasteur, 25 June 2024, https://clinicaltrials.gov/study/NCT03691610 MET61: Post booster, MenACYW -TT seroprotection rates were high and
comparable to those for MenACWY -CRM for all 4 serogroups
Secondary objective was met: Post-second vaccination at 12 -13 months, group 1 demonstrated that at D30, the lower limit of the 95%
confidence interval (CI) for the difference in subjects achieving seroprotection (hSBA ≥1:8) for serogroups A, C, W, and Y was above - 10%
compared to group 2.
MET61 : Geometric mean of hSBA antibody titers pre- and post -2nd
vaccination with MenACYW -TT and MenACWY -CRM
32Summary of secondary immunogenicity results
D, day; GMT, geometric mean titer ; hSBA , human serum bactericidal assay;
95% CI calculated using calculation for normal distribution on log10( titer) following by antilog transformation
Group 1: MenACYW -TT vaccine + routine pediatric vaccines at 6 to 7 months of age and 12 to 13 months of age
Group 2: MEenACWY -CRM vaccine + routine pediatric vaccines at 6 to 7 months of age and 12 to 13 months of ageSecondary objective: At D0 (pre- dose 1), baseline hSBA GMTs for serogroups A, C, Y, and W were comparable between groups, but at D30
post-dose 2 (12– 13 months), they were higher in Group 1 for all serogroups
Summary of geometric means of hSBA titers at pre-dose D1 and D30 after the 2nd vaccination at 12 -13 months dose - Per-Protocol Analysis Set 2
Serogroup A C Y W32Geometric means of hSBA
titers
Log scale
4.73 4.64
2.57 2.48 2.54 2.37 2.23 2.311841191473
319423
133442
106
110100100010000
Group 1 Group 2 Group 1 Group 2 Group 1 Group 2 Group 1 Group 2D1 D30
MET61 : Geometric mean hSBA titers pre - and post -2nd vaccination with
MenACYW -TT and MenACWY -D
33Summary of secondary immunogenicity results
D, day; GMT, geometric mean titer ; hSBA , human serum bactericidal assay;
95% CI calculated using calculation for normal distribution on log10( titer) following by antilog transformation
Group 3: MenACYW -TT vaccine at 17 to 19 months of age and 20 to 23 months of age
Group 4: MenACWY -D at 17 to 19 months of age and 20 to 23 months of ageSecondary objective: At D0 (pre- dose 1), hSBA GMTs were comparable between groups, but at 30 days post -dose 2 (20– 23 months), they
were higher in Group 3 for all serogroups
Summary of geometric means of hSBA titers at pre-dose D1 and D30 after the 2nd vaccination at 20 -33 months dose - Per-Protocol Analysis Set 2
Serogroup A C Y W33Geometric means of hSBA
titers
Log scale
4.293.432.1 2.41 2.44 2.442.02 2.1245
13.21727
59.4284
45.5202
25
110100100010000
Group 3 Group 4 Group 3 Group 4 Group 3 Group 4 Group 3 Group 4D1 D30
Group 3 Group 4 Group 3 Group 4 Group 3 Group 4 Group 3 Group 4
Summary of immunogenicity findings
Seroresponses at day 30 following the first dose of MenACYW -TT vaccine co -administered with routine pediatric vaccines were non-
inferior to those seen after administration of a primary dose of MenACWY -CRM with routine pediatric vaccines MET61: Summary of results
• The percentages of participants in both groups with ≥4 -fold rise in titers pre- vs 30 days post -dose 2 were
comparable for all 4 serogroupsSix to 7 months following administration of a dose of MenACYW -TT vaccine to infants 6 -7 months of age , geometric mean
titers (GMTs) were comparable to those seen after administration of a dose of MenACWY -CRM for serogroup A and higher for
serogroups C, W, and Y
Thirty days after dose 2 administered at 20 -23 months of age , the hSBA GMTs were higher for all serogroups in
participants administrated MenACYW -TT vaccine compared to those who received MenACWY -D
• The percentages of participants with a ≥ 4-fold rise in hSBA GMTs for serogroups C, Y, and W were comparable
between the 2 vaccine groups and higher for serogroup A after MenACYW -TT vaccine administration compared to
MenACWY -D
MenACYW -TT vaccine is immunogenic and demonstrates an acceptable safety profile
when administered to infants 6 months through 23 months of age in a 2-dose
schedule .34
Immunogenicity and Safety Study of a Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers.
ClinicalTrials.gov , Sanofi Pasteur, 25 June 2024, https://clinicaltrials.gov/study/NCT03691610
Conclusion
MenACYW -TT demonstrated robust immunogenicity & reassuring safety
profile in infants & toddlers starting vaccination as early as 6 weeks of
age
•The expanded indication for MenACYW -TT is a valuable public health option to facilitate
immunization across the lifespan from 6 weeks & above
•Immunogenicity results demonstrate non -inferior immune responses, administered with
routine pediatric vaccines, compared to currently licensed MenACWY conjugate vaccines
•No unexpected safety concerns were found in infants and toddlers (from 6 weeks to 23
months) compared to the safety profile in individuals ≥2 years and other licensed
MenACWY conjugate vaccines
•No relevant safety profile differences were observed based on sex or race
•The safety profile of 237 infants with a history of preterm birth (31-36 weeks
gestational age)** was comparable to infants who had been born full -term, with no new
safety concerns or AEs leading to study discontinuation
36** all prematurely born infants were either enrolled in studies MET41 and MET42
Thank
you