Meningococcal A,C,Y,W135 Conjugate Vaccine (Menactra TM ) Lucia H. Lee CBER, FDA Vaccines and Related Biological Products Advisory Committee Meeting September

Meningococcal A,C,Y,W135 Meningococcal A,C,Y,W135 Conjugate Vaccine Conjugate Vaccine (Menactra(MenactraTMTM))

Lucia H. LeeLucia H. Lee

CBER, FDACBER, FDA

Vaccines and Related Biological ProductsVaccines and Related Biological ProductsAdvisory Committee MeetingAdvisory Committee Meeting

September 22, 2004September 22, 2004

Aventis Pasteur, Inc.Aventis Pasteur, Inc.

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OutlineOutline

Proposed Basis for Licensure:Proposed Basis for Licensure: 11-55 years old 11-55 years old Clinical StudiesClinical Studies

Efficacy (Immunogenicity)Efficacy (Immunogenicity)• MTA-02, MTA-09MTA-02, MTA-09

SafetySafety• MTA-04, MTA-09MTA-04, MTA-09

Concomitant vaccinesConcomitant vaccines• MTA-12MTA-12

Study ResultsStudy Results Questions for the CommitteeQuestions for the Committee

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Proposed Basis for Licensure: Proposed Basis for Licensure: 11-55 years old11-55 years old

EfficacyEfficacy inferred from immunogenicity data inferred from immunogenicity data Non-inferiority to Non-inferiority to MenomuneMenomune®®,, a U.S. licensed a U.S. licensed

meningococcal ACYW135 polysaccharide vaccinemeningococcal ACYW135 polysaccharide vaccine Immune correlate:Immune correlate: serum bactericidal antibody serum bactericidal antibody

Demonstration ofDemonstration of safetysafety Non-inferiority to MenomuneNon-inferiority to Menomune®®

Demonstration ofDemonstration of lot consistencylot consistency

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Immunogenicity Studies:Immunogenicity Studies:MTA-02 and MTA-09MTA-02 and MTA-09

# Participants Enrolled# Participants Enrolled

Study Study Age (yrs)Age (yrs) MenactraMenactra MenomuneMenomune®®

MTA-02MTA-02 11-18y11-18y 440440 441441

8484 8181

MTA-09MTA-09 18-55y18-55y 13841384 11701170

5050 5050

Serum bactericidal assay- baby rabbit complementSerum bactericidal assay- baby rabbit complement Menactra bactericidal antibody responses compared to Menactra bactericidal antibody responses compared to

MenomuneMenomune®®, using baby rabbit C’ and human C’, using baby rabbit C’ and human C’

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Serum bactericidal assay- baby rabbit complement (SBA-BR)Serum bactericidal assay- baby rabbit complement (SBA-BR)

Serum bactericidal assay- human complement (SBA-H)Serum bactericidal assay- human complement (SBA-H)

Study MTA-02Study MTA-02 (11-18 years old) (11-18 years old)• C, Y, W135C, Y, W135• AA (Menactra n=50, Menomune(Menactra n=50, Menomune®® n=52) n=52)

Study MTA-09Study MTA-09 (18-55 years old) (18-55 years old)• Y, W135Y, W135

Reverse cumulative distribution curvesReverse cumulative distribution curves

Seroresponse RateSeroresponse Rate

Seroconversion RateSeroconversion Rate

Immunogenicity: Immunogenicity: Menactra Compared to MenomuneMenactra Compared to Menomune®®, using SBA, using SBA

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Menactra Compared to MenomuneMenactra Compared to Menomune®®::Reverse Cumulative Distribution Curves of Reverse Cumulative Distribution Curves of Antibody Titer Post-vaccination [Antibody Titer Post-vaccination [SBA-BRSBA-BR]]

11-18 years old11-18 years old

Serogroup ASerogroup A Serogroup CSerogroup C

Serogroup YSerogroup Y Serogroup W135Serogroup W135

Menactra Menomune

711-18 years old

Serogroup ASerogroup A Serogroup CSerogroup C

Serogroup YSerogroup Y Serogroup W135Serogroup W135

Menactra Compared to Menomune®:Menactra Compared to Menomune®:Reverse Cumulative Distribution Curves ofReverse Cumulative Distribution Curves of

Antibody Titer Post-vaccination [Antibody Titer Post-vaccination [SBA-HSBA-H]]

Menactra Menomune

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Menactra Compared to MenomuneMenactra Compared to Menomune®®::Seroresponse Rate (11-18 years old) Seroresponse Rate (11-18 years old) SBA-BRSBA-BR

Study MTA-02: SBA-BR Seroresponse Rate

0

10

20

30

40

50

60

70

80

90

100

A C Y W

Serogroup

Pe

rce

nta

ge

MenomuneMenactra

SBA-BR response: defined as SBA-BR response: defined as >>4-fold Increase in antibody titer post-vaccination, 4-fold Increase in antibody titer post-vaccination, compared to baselinecompared to baseline

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Menactra Compared to MenomuneMenactra Compared to Menomune®®::Seroresponse Rate (11-18 years old) Seroresponse Rate (11-18 years old) SBA-HSBA-H

Study MTA-02: SBA-H Seroresponse Rate

0

10

20

30

40

50

60

70

80

90

100

A C Y W

Serogroup

Per

cen

tag

e

Menomune

Menactra

SBA-H response: defined as an antibody titer SBA-H response: defined as an antibody titer >>1: 4 post-vaccination1: 4 post-vaccination

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Menactra Compared to MenomuneMenactra Compared to Menomune®®, using SBA, using SBA

Serum bactericidal assay:Serum bactericidal assay: Menactra and Menomune bactericidal antibody response, Menactra and Menomune bactericidal antibody response,

using BR or H complement, supported the same using BR or H complement, supported the same conclusion.conclusion.

• RCD curves overlapped, for Menactra and Menomune RCD curves overlapped, for Menactra and Menomune antibody titers measured post-vaccination, with each source antibody titers measured post-vaccination, with each source of complementof complement

• Similar seroresponse and seroconversion rateSimilar seroresponse and seroconversion rate

• Similar immunogenicity profile in adultsSimilar immunogenicity profile in adults

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Meningococcal A,C,Y W135 Meningococcal A,C,Y W135 Conjugate VaccineConjugate Vaccine

(Menactra(MenactraTMTM))

ImmunogenicityImmunogenicity Study MTA-02: 11-18 years oldStudy MTA-02: 11-18 years old Study MTA-09: 18-55 years oldStudy MTA-09: 18-55 years old

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Immunogenicity:Immunogenicity:MTA-02 and -09 Study DesignMTA-02 and -09 Study Design

Design:Design: Randomized, modified double blind, multi-center (USA), Randomized, modified double blind, multi-center (USA),

active-controlled trialactive-controlled trial

Enrollment:Enrollment: MTA-02: 11-18 years oldMTA-02: 11-18 years old MTA-09: 18-55 years oldMTA-09: 18-55 years old

Vaccine administration:Vaccine administration:• Menactra: single dose, IMMenactra: single dose, IM• MenomuneMenomune®® : single dose, SC: single dose, SC

Serum samples were obtained pre- and 28 days Serum samples were obtained pre- and 28 days post-vaccination. post-vaccination.

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Primary endpoint:Primary endpoint: Proportion of participants with a Proportion of participants with a >>4-fold rise in SBA-BR 4-fold rise in SBA-BR

titer 28 days post-vaccination, compared to baseline, titer 28 days post-vaccination, compared to baseline, for each serogroupfor each serogroup

Other measurements of immune response:Other measurements of immune response: SBA-BR geometric mean titerSBA-BR geometric mean titer Seroconversion rateSeroconversion rate IgG and IgM, measured by ELISA (MTA-02)IgG and IgM, measured by ELISA (MTA-02)

Immunogenicity:Immunogenicity:MTA-02 and -09 EndpointsMTA-02 and -09 Endpoints

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Primary Hypothesis: Primary Hypothesis: To demonstrate that 28 days after vaccination, Menactra To demonstrate that 28 days after vaccination, Menactra is non-inferior to Menomuneis non-inferior to Menomune®®

MTA-02:MTA-02: Upper limit of the 1-sided 95% CI of Upper limit of the 1-sided 95% CI of ppMenomune®Menomune® – – ppMenactraMenactra is <0.10 is <0.10

MTA-09:MTA-09: Upper limit of the 2-sided 95% CI Upper limit of the 2-sided 95% CI of of ppMenomune®Menomune® – – ppMenactraMenactra is <0.10 is <0.10

p : p : proportion of seroresponders proportion of seroresponders • participants with a participants with a >>4-fold rise in SBA-BR titer 28 days after 4-fold rise in SBA-BR titer 28 days after

vaccination, as compared to baseline, for each serogroupvaccination, as compared to baseline, for each serogroup

Immunogenicity:Immunogenicity:Statistical HypothesisStatistical Hypothesis

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Study MTA-02 Study MTA-02 (11-18 years old)(11-18 years old)Results- Primary Immunogenicity AnalysisResults- Primary Immunogenicity Analysis

Proportion of Participants with > Four-fold Increase in SBA-BR 28 Days Post-vaccination, Compared to Baseline

Menomune®

Menactra

Difference Upper Limit of the

Upper Limit of the

Serogroup N= 423 N= 423 (pMenomune® - 1-sided 95% CI 2-sided 95% CI

pMenomune® pMenactrapMenactra) of the Difference of the Difference

A 0.924 0.926 -0.002 0.027 0.033

C 0.886 0.917 -0.031 0.003 0.009

Y 0.801 0.818 -0.017 0.028 0.036

W-135 0.952 0.966 -0.014 0.008 0.013

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Study MTA-09Study MTA-09 (18-55 years old) (18-55 years old)Results- Primary Immunogenicity AnalysisResults- Primary Immunogenicity Analysis

Proportion of Participants with > Four-fold Increase in SBA-BR 28 Days Post-vaccination, Compared to Baseline

Menomune® Menactra

Upper Limit of the

Serogroup N= 1098 N= 1280 Difference 2-sided 95% CI

pMenomune® pMenactra (pMenomune® - pMenactra) of the Difference

A 0.846 0.805 0.041 0.072

C 0.897 0.885 0.012 0.037

Y 0.794 0.735 0.059 0.093

W-135 0.944 0.894 0.050 0.072

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SafetySafety

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Overall Safety Database

# Participants enrolled

Age group

Menactra Menomune

n n

11-14 years 1636 490

15-25 years 4078 1578

26-55 years 1957 973

Total for 11-55y 7672 3041



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Menactra Menomune®

ITT population for safety* 7670 (100%) 3041 (100%)Completed 28 day follow-up 7500 (98%) 3004 (99%)

Safety follow-up 6m post-vaccination obtained 5676 (100%) 3041 (100%)Completed 6 month follow-up 5453 (96%) 2923 (96%)

MTA-02: 11-18 years old 436 435MTA-04: 11-18 years old 2251 962MTA-09: 18-55 years old 1301 1099MTA-14: 18-55 years old 1464 427

Overall Participant Safety Profile

* ITT population for safety included randomized participants who received one dose of any study vaccine. Analysis was performed according to the vaccine received.



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Safety Studies:Safety Studies:MTA-04 and MTA-09MTA-04 and MTA-09

# Participants Enrolled# Participants Enrolled

Study Study Description Description Age (yrs)Age (yrs) MenactraMenactra MenomuneMenomune®®

MTA-04MTA-04 SafetySafety 11-18y11-18y 22702270 972972

[[15-18y15-18y ~75%~75% ~75%~75%] ]

MTA-09MTA-09 Safety + ImmunogenicitySafety + Immunogenicity 18-55y18-55y 13841384 11701170

[[18-25y18-25y ~60%~60% ~60% ~60% ]]

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Safety:Safety:MTA-04 and -09 Study DesignMTA-04 and -09 Study Design

Primary Objective:Primary Objective: To compare the relative frequency of a To compare the relative frequency of a solicited severe systemic reaction among Menactra and solicited severe systemic reaction among Menactra and MenomuneMenomune®® recipients recipients

Vaccine administration:Vaccine administration:

Menactra: IM, MenomuneMenactra: IM, Menomune®®: SC: SC Study personnel administering the vaccine differed from Study personnel administering the vaccine differed from

personnel collecting the safety datapersonnel collecting the safety data

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Local reactionsLocal reactions Pain, induration, erythema, swellingPain, induration, erythema, swelling

Systemic reactionsSystemic reactions Fever (oral temperature), headache, fatigue, malaise, chills, Fever (oral temperature), headache, fatigue, malaise, chills,

arthralgia, anorexia, vomiting, diarrhea, seizures, rasharthralgia, anorexia, vomiting, diarrhea, seizures, rash

Safety:Safety: MTA-04 and -09 MTA-04 and -09

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Safety:Safety:MTA-04 and -09 MTA-04 and -09 Statistical Analysis PlanStatistical Analysis Plan

Primary Hypothesis:Primary Hypothesis:

To demonstrate that Menactra is non-inferior to To demonstrate that Menactra is non-inferior to Menomune Menomune pp: proportion of participants with at least one severe : proportion of participants with at least one severe

systemic reaction during the 7 day period following systemic reaction during the 7 day period following vaccinationvaccination

Upper limit of the two-sided 90% CI of Upper limit of the two-sided 90% CI of ppMenactraMenactra / / ppMenomune®Menomune® is is

less than 3less than 3 Current CBER requirements: two-sided 95% CICurrent CBER requirements: two-sided 95% CI

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Severe Systemic Reaction:Severe Systemic Reaction: Fever Fever

• T>40.0C (oral)T>40.0C (oral) Headache, fatigue, malaise, chills, arthralgiaHeadache, fatigue, malaise, chills, arthralgia

• Disabling, requiring bed rest or analgesicsDisabling, requiring bed rest or analgesics Anorexia, vomitingAnorexia, vomiting

• >>3 episodes 3 episodes DiarrheaDiarrhea

• >>5 episodes 5 episodes SeizuresSeizures

• AnyAny RashRash

• For analysis purposes, all rashes (Days 0-7) were designated as For analysis purposes, all rashes (Days 0-7) were designated as severesevere


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Intent-to-treat Population for Safety:Intent-to-treat Population for Safety:

Randomized participants who received one dose of vaccineRandomized participants who received one dose of vaccine

Safety information was available Safety information was available

Analyses were performed according to the vaccine Analyses were performed according to the vaccine received received


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Study Results:Study Results: MTA-04 (11-18 years old)MTA-04 (11-18 years old)



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Study MTA-04:Study MTA-04: Ages 11-18 years old Ages 11-18 years oldIncidence of Any Local Reactions (Days 0-7)Incidence of Any Local Reactions (Days 0-7)

* non-overlapping 95% CI between the two vaccine groups Pain: 0=none1= (mild) symptom present, but arm movement not affected2= (moderate) limits usual arm movement

Menactra Menomune®

N= 2264 N= 970

Reaction Severity % 95% CI % 95% CI

Pain Any 59.2* 57.1, 61.2 28.7 25.8, 31.6

Mild 46.2* 44.1, 48.2 26.1 23.3, 29.0

Moderate 12.8* 11.4, 14.2 2.6 1.7, 3.8

Induration Any 15.7* 14.2, 17.2 5.2 3.9, 6.7

Redness Any 10.9* 9.7, 12.3 5.7 4.3, 7.3

Swelling Any 10.8* 9.6, 12.2 3.6 2.5, 5.0

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Study MTA-04:Study MTA-04: Ages 11-18 years old Ages 11-18 years oldIncidence of Rash (Days 0-7)Incidence of Rash (Days 0-7)

N=51 (37 Menactra, 14 MenomuneN=51 (37 Menactra, 14 Menomune®®))

Local rash:Local rash:• Injection site: n= 14Injection site: n= 14 (11 Menactra, 3 Menomune(11 Menactra, 3 Menomune®®))

• Non-specific local rashNon-specific local rash Extremities > trunk > neck or faceExtremities > trunk > neck or face Median duration: 2 days (range 40 minutes to 2 months)Median duration: 2 days (range 40 minutes to 2 months)

Generalized rash:Generalized rash: n=3 n=3• Itchy, blanching Itchy, blanching (1 Menactra, 1 Menomune(1 Menactra, 1 Menomune®®))

• Non-blanching, red, raised Non-blanching, red, raised

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Study MTA-04:Study MTA-04: Ages 11-18 years old Ages 11-18 years oldResults- Primary Safety AnalysisResults- Primary Safety Analysis

Note: For analysis purposes, all rashes were counted as severe solicited systemic reactions. Also, for each reaction, each participant is counted no more than once.

Number and Proportion of Participants 11-18 Years Old With At Least One Severe Solicited Systemic Reaction

Menactra Menomune® Upper

Limit of Upper

Limit of

N= 2265 N= 970 Ratio the 2-sided

90% CIthe 2-sided

95% CI

n pMenactra n pMenomune®

(pMenactra /

pMenomune® )of the Ratio

of the Ratio

97 0.043 25 0.026 1.7 2.4 2.6

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Study MTA-04:Study MTA-04: Ages 11-18 years old Ages 11-18 years oldSevere Systemic Reactions (Days 0-7)Severe Systemic Reactions (Days 0-7)

Menactra Menomune®

N= 2265 N= 970

% %

Severe systemic reactions (+ rash) 4.3% 2.6%

Severe systemic reactions (- rash) 2.7% 1.2%

Participants with multiple severe systemic AEs: 1.1% 0.3%

5 severe systemic AEs 0.1% 0.0%




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Study Results:Study Results: MTA-09 (18-55 years old)MTA-09 (18-55 years old)



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Study MTA-09: Study MTA-09: Incidence of Local Pain (Days 0-7)Incidence of Local Pain (Days 0-7)Ages 18-25 and 26-55 years oldAges 18-25 and 26-55 years old

Pain: 0=none1= (mild) symptom present, but arm movement not affected2= (moderate) limits usual arm movement3= (severe) disabling

Menactra Menomune®

Local Pain Severity % 95% CI % 95% CI

Age 18-25 years Any 61.1 57.5, 64.5 51.8 47.9, 55.6

Mild 45.8 42.3, 49.4 47.9 44.1, 51.8

Moderate 15.2 12.9, 18.0 3.7 2.5, 5.5

Severe 0.0 0.0, 0.0 0.2 0.0, 0.9

Age 26-55 years Any 45.1 41.2, 49.1 43.6 39.4, 47.9

Mild 38.2 34.4, 42.1 40.9 36.7, 45.2

Moderate 6.5 4.8, 8.7 2.7 1.6, 4.5

Severe 0.5 0.2, 1.4 0.0 0.0, 0.7

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Study MTA-09:Study MTA-09: Ages 18-55 years old Ages 18-55 years oldResults- Primary Safety AnalysisResults- Primary Safety Analysis

Note: For analysis purposes, all rashes were counted as severe solicited systemic reactions. Also, for each reaction, each participant is counted no more than once.

Number and Proportion of Participants 18-55 Years Old With At Least One Severe Solicited Systemic Reaction

Menactra Menomune® Upper

Limit of Upper

Limit of

N= 1371 N= 1159 Ratio the 2-sided

90% CIthe 2-sided

95% CI

n pMenactran pMenomune®

(pMenactra /

pMenomune® )of the Ratio

of the Ratio

52 0.038 30 0.026 1.5 2.1 2.3

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Study MTA-09:Study MTA-09: Ages 18-55 years old Ages 18-55 years oldSevere Systemic Reactions (Days 0-7)Severe Systemic Reactions (Days 0-7)

Menactra Menomune®

N= 1371 N= 1159

% %

Severe systemic reactions (+ rash) 3.8% 2.6%

Severe systemic reactions (- rash) 2.6% 1.9%

Participants with multiple severe systemic AEs: 1.1% 0.7%






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Serious Adverse eventsSerious Adverse events

(all trials combined)(all trials combined)



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Two deathsTwo deaths 25-year old woman25-year old woman

• Motor vehicle accident 109 days following Menactra vaccinationMotor vehicle accident 109 days following Menactra vaccination

35-year old man 35-year old man • Cardiopulmonary arrest following drug overdose 72 days after Cardiopulmonary arrest following drug overdose 72 days after

Menomune vaccinationMenomune vaccination

Investigator considered event possibly related to Investigator considered event possibly related to vaccinationvaccination 17- year old Menactra participant with severe esophagitis17- year old Menactra participant with severe esophagitis

Hospitalized six days following immunization. A plausible cause Hospitalized six days following immunization. A plausible cause for the event included a history of a sports-related back injury, four for the event included a history of a sports-related back injury, four weeks prior to enrollment, and extensive NSAID use thereafter. weeks prior to enrollment, and extensive NSAID use thereafter.

Safety:Serious Adverse Events (all trials submitted to BLA)

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Concurrent ImmunizationsConcurrent Immunizations Study MTA-12: TdStudy MTA-12: Td



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Concurrent Immunizations:Concurrent Immunizations:Study MTA-12Study MTA-12

Day 0 Day 28

Menactra + Td Saline placebo

Td + saline placebo Menactra

Group B:

Group A:

11-17 years old

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Study MTA-12: TdStudy MTA-12: Td Antibody response to Antibody response to

meningococcal componentsmeningococcal components



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Study MTA-12:Study MTA-12:% with SBA-BR % with SBA-BR >>Four-fold Increase in SBA-BR Four-fold Increase in SBA-BR Antibody TiterAntibody Titer

Percentage of Participants 11-17 Years Old with > 4-fold Increase in SBA-BR Antibody Titer, 28 days after Menactra vaccination, compared to Baseline

Serogroup

Group A Group BDifference(Group B-

Group A)

Td+ Menactra, Then Placebo

Td + Placebo, Then Menactra

N=478 N=465

% % %

A 90.1 90.6 0.5%

C 91.2 82.4 -8.8%

Y 85.8 65.1 -20.7%

W-135 96.3 87.7 -8.7%

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Study MTA-12: Study MTA-12: Ages 11-17 years oldAges 11-17 years oldSBA-BR GMT, 28d after Menactra vaccinationSBA-BR GMT, 28d after Menactra vaccination

SBA-BR GMT, 28 Days after Menactra Vaccination

Group A Group B

Td + MenactraTd + Menactra Td, then MenactraTd, then Menactra

A 11313 10391

C 5059 2136

Y 3391 1331

W135 4195 1339

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Study MTA-12: TdStudy MTA-12: Td SafetySafety



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Study MTA-12: Study MTA-12: Local Pain after [Td + Menactra] vaccination Local Pain after [Td + Menactra] vaccination (Days 0-7)(Days 0-7)

Concomitant Vaccine Group: Td and Menactra Injection sites

Group A N=505

Group AN=505

Td + Menactra, Td + Menactra,

Then Placebo Then Placebo

MenactraInjection site

Td Injection site


Pain

Any 52.9 48.4, 57.3 70.9 66.7, 74.8

Mild 42.2 37.8, 46.6 48.3 43.9, 52.8

Moderate 10.7 8.1, 13.7 22.4 18.8, 26.3

Severe 0.0 0.0, 0.7 0.2 0.0, 1.1

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Menactra Local Adverse Reactions (Days 0-7)

Group A (N= 505) Group B (N= 505)

Td + Menactra, Td + Placebo,

Then Placebo Then Menactra

MenactraInjection site

Menactra Injection site


Redness Any 12.1 9.4, 15.2 11.1 8.5, 14.2

Swelling Any 11.7 9.0, 14.8 13.1 10.3, 16.3

Induration Any 17.0 13.9, 20.6 15.4 12.4, 18.9

Pain Any

52.9 48.4, 57.3 53.5 49.0, 57.9

Study MTA-12: Study MTA-12: Menactra local reactions after 1Menactra local reactions after 1stst (Group A) and 2 (Group A) and 2ndnd (Group B) vaccination(Group B) vaccination

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Study MTA-12:Study MTA-12: Diphtheria GMTDiphtheria GMT (Day 0, 28 days after Td) (Day 0, 28 days after Td)

Diphtheria GMT

020406080

100120140

GM

T (

IU/m

l)

Td + Menactra 0.4 120.9

Td, then Menactra 0.4 8.4

Td pre-vaccination 28 days post-Td

46

SummarySummary



47

SummarySummary

Primary immunogenicity hypotheses to demonstrate Primary immunogenicity hypotheses to demonstrate non-inferiority of Menactra compared to Menomunenon-inferiority of Menactra compared to Menomune®® were achieved, for each serogroup. were achieved, for each serogroup. Proportion of participants with Proportion of participants with >>4-fold increase in SBA-4-fold increase in SBA-

BR titer, 28 days after vaccination, compared with BR titer, 28 days after vaccination, compared with baselinebaseline

A difference in antibody response to meningococcal A difference in antibody response to meningococcal components was noted in the group receiving Td prior components was noted in the group receiving Td prior to Menactra, and the group receiving Menactra and Td to Menactra, and the group receiving Menactra and Td concomitantly.concomitantly.

48

Increased frequency of local and systemic reactions Increased frequency of local and systemic reactions was observed in Menactra participants, compared to was observed in Menactra participants, compared to MenomuneMenomune®®. . Difference in % of participants with multiple severe Difference in % of participants with multiple severe

systemic reactions was not statistically significantsystemic reactions was not statistically significant Safety hypotheses to demonstrate non-inferiority of Safety hypotheses to demonstrate non-inferiority of

Menactra to MenomuneMenactra to Menomune®® were achieved were achieved

Cont. SummaryCont. Summary

Documents

Meningococcal A,C,Y,W135 Conjugate Vaccine (Menactra TM ) Lucia H. Lee CBER, FDA Vaccines and Related Biological Products Advisory Committee Meeting September