1

FluMist®

Influenza Virus Vaccine Live, Intranasal

MedImmuneGaithersburg, Maryland

Edward Connor, M.D. Executive VP, Clinical DevelopmentChief Medical Officer

2

Sponsor Team

Sponsor Project Team Robert Walker, M.D. FluMist Project Director George Kemble, Ph.D. Head of Research, MedImmune Vaccines Iksung Cho, MS Head of Biostatistics Micki Hultquist, MS FluMist Project Lead Statistician

External Investigators/Advisors Robert Belshe, M.D. Professor, Internal Medicine/Infectious Disease

Director, Center for Vaccine DevelopmentSaint Louis University School of Medicine

Kathryn Edwards, M.D. Professor of Pediatrics

Vice Chair for Clinical Research in PediatricsDirector of Pediatric Clinical Research Division of Pediatric Infectious DiseasesVanderbilt University School of Medicine

Dereck Weycker, Ph.D. Policy Analysis, Inc. Janet Wittes, Ph.D. Statistics Collaborative, Inc. Pamela Zeitlin, M.D., Ph.D. Professor of Pediatrics and Physiology

Director, Pediatric Respiratory SciencesJohns Hopkins University School of Medicine

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Sponsor Presentation

Introduction and Overview Data on efficacy of FluMist in children <5 years of age Data on safety of FluMist in children <5 years of age Post-marketing studies Conclusions

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Influenza and Vaccination

Influenza is the leading cause of vaccine-preventable mortality and morbidity in the U.S.

Vaccination is the primary method for preventing illness and severe complications related to influenza

Antigenic mismatch between vaccines and circulating strains is common and complicates influenza prevention

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Influenza in Children

Rates of influenza infection are highest among children Hospitalization rates among young children similar to elderly Significant burden of outpatient clinic visits and ER visits

Annual vaccination is recommended for all children 6-59 months of age in the U.S.

Trivalent inactivated vaccine (TIV) is the only currently licensed product for children <5 years of age Single manufacturer for children <4 years of age

Thompson et al, J Am Med Assoc 289:179, 2003 Poehling et al, N Engl J Med 355:31, 2006 ACIP Recommendations: MMWR 55:RR-10, 2006 AAP Recommendations: Pediatrics 119: 846, 2007AAFP Practice Guidelines: Am Fam Phys 74:665, 2006

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Live, cold-adapted, temperature-sensitive, attenuated influenza virus vaccine

Trivalent (A/H1N1, A/H3N2, B) 107 FFU of each strain per dose Dose: 0.2 mL intranasal spray (0.1 mL per nostril) Storage: 2-8ºC (refrigerator) Contains no preservatives (e.g., no thimerosal)

FluMist®

Product Characteristics

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FluMist® Regulatory Milestones

2003 FluMist (frozen) approved for healthy individuals 5 to 49 years of age

2003-2007 Commercial product available

January 2007 Refrigerated FluMist approved for healthy individuals 5 to 49 years of age

8

FluMist® Post Licensure Safety (5-49 years of age)

Approximately 7M doses have been distributed for commercial use from 2003 to 2007

No new safety signals have been identified since licensure VAERS data from first 2 seasons1 Post-marketing safety study (N = 45,000) 2002-20062

1 Izurieta et al, J Am Med Assoc 294:2720, 2005 2 Baxter et al, PAS 2007

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FluMist®

Rationale for Lower Age Limit in Initial Approval

MedImmune did not seek an indication in children <5 years

Wheezing signal in placebo-controlled safety study

Further data needed to understand the signal

Bergen et al, Pediatr Infect Dis J 23:138, 2004 Belshe et al, Clin Infect Dis 39:920, 2004

Age (mo) Outcome

IncidenceRelative Risk

(90% CI)FluMist

N=2032

Placebo

N=1025

12–59 Asthma 0.69% 0.20%3.53

(1.10, 15.66)

12–59Asthma +Wheezing

1.23% 0.78%1.58

(0.82, 3.20)

Study AV019 Post Hoc Analysis of Diagnostic Codes

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FluMist® Background for Expansion of Indicated Population

Two published studies suggested better efficacy of FluMist compared to TIV in children 6-71 mos with recurrent RTI (N=2187)1 & 6-17 yrs with asthma (N=2229)2

53% & 35% fewer cases of influenza (predominantly matched B) No safety signals identified Open-label, not conducted under US IND

IND studies of efficacy and safety of FluMist in children <59 months of age Study AV006 (NIH CRADA with Aviron) Study D153-P501 (Wyeth) Study MI-CP111

1 Ashkenazi et al, Pediatr Infect Dis J 25:870, 2006 2 Fleming et al, Pediatr Infect Dis J 25:860, 2006

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FluMist® Principal Findings for Children <5 years (IND Studies)

Efficacy High levels of efficacy against influenza Significantly higher efficacy compared to TIV in MI-CP111 Cross-protection against mismatched A/H3N2, including better cross-

protection compared to TIV in MI-CP111

Safety Further evaluation is needed in children 6-11 months of age and in

children 12-59 months with a history of wheeze/asthma For children without a history of wheeze/asthma

Safety established in children 24-59 months of age Risk-benefit warrants availability for children 12-23 months of age

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FluMist® Proposed Expanded Indicated Population

Children 12 to 59 months of age without a history of wheeze/asthma

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EfficacyFluMist® in Children <5 Years of Age

High levels of efficacy against influenza Significantly higher efficacy compared to TIV in MI-CP111 Cross-protection against mismatched A/H3N2, including

better cross-protection compared to TIV in MI-CP111

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Studies AV006 and D153-P501Placebo-Controlled Efficacy Studies

1 Belshe et al. N Engl J Med. 338:1405-1412, 19982 Belshe et al. J Pediatr. 136:168-175, 20003 Tam et al. Pediatr Infect Dis J. In press.

AV0061,2 D153-P5013

N 1,602 3,174

Years/Location 1996-98, US 2000-02, Asia (8 countries)

Design Randomized (2:1), DB Randomized (3:2), DB

Age at entry 15-71 months 12-35 months

Year 1 strains Matched A/H3N2, B Matched A/H1N1, A/H3N2, B

Year 2 strains Mismatched A/H3N2 Matched A/H3N2

Two placebo-controlled studies assessed efficacy vs. all three influenza subtypes, including mismatched A/H3N2

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FluMist® Efficacy in Vaccine-naïve Children

Year One Efficacy by Strain (Matched)

Study D153-P5012

0

10

20

30

40

50

60

70

80

90

100

AnyStrain

H3N2 B AnyStrain

H1N1 H3N2 B

93.4% 96.0% 90.5%

72.9%80.9%

90.0%

44.3%

Study AV0061

Influenza Strain1 Belshe et al. N Engl J Med. 338:1405-1412, 19982 Tam et al. Pediatr Infect Dis J. In press.

Efficacy estimates are for matched strains, the studies’ primary endpoint

Effic

acy

(%) w

ith 9

5% C

I

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FluMist® Efficacy in Previously Vaccinated Children: Year Two Efficacy by Strain

0

10

20

30

40

50

60

70

80

90

100

Any Strain H3N2 Any Strain H3N2

Effic

acy

(%) w

ith 9

5% C

I

Influenza Strain

87.0% 86.7% 84.3% 86.3%

AV006 estimates are for all strains because 94% of strains were mismatchedD153-P501 estimates are for matched strains

Study D153-P5012Study AV0061

1 Belshe et al. N Engl J Med. 338:1405-1412, 19982 Tam et al. Pediatr Infect Dis J. In press.

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Study MI-CP111Pivotal Comparative Trial in Children <5 Years of Age

Pivotal trial to evaluate safety and efficacy of FluMist compared to TIV

Allows assessment of the benefits and risks of both vaccines in children 6-59 months of age

Belshe et al, N Engl J Med 356:685, 2007

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Study MI-CP111Design

Randomized, double-blind, TIV-controlled, multinational Children 6-59 months of age (N=8,475)

Excluded only recent wheezing, history of severe asthma, immunocompromised

Stratification factors Age (6-23, 24-35, 36-59 months), country, previous influenza

vaccination, and history of >3 wheezing illnesses Stratification of 24-35 months to balance children receiving different TIV

licensed dosages (children <3 years receive 0.25 mL)

Pre-specified analyses for children 6-23 months and 24-59 months Enrollment of children 6-23 months was increased to enable robust

subgroup analysis

Belshe et al, N Engl J Med 356:685, 2007

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Study MI-CP111Design

Primary efficacy endpoint was culture-confirmed modified CDC influenza-like illness (mCDC-ILI) against matched strains Increased temperature (100ºF oral or equivalent) plus cough, sore

throat or runny nose/nasal congestion on same or consecutive days Symptoms must be within +/- 7 days of positive culture

According to protocol (ATP) and intent-to-treat (ITT) analyses

Belshe et al, N Engl J Med 356:685, 2007

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Study MI-CP111Baseline Characteristics

TIV

N=4232

FluMist

N=4243

Mean Age (mos) 25.6 25.7

Male 51.4% 51.3%

White, Non-Hispanic 80.4% 80.2%

Previously vaccinated 22.5% 22.3%

Prior wheeze history Any 3 or more

20.7% 5.7%

21.7% 6.5%

ITT Population

Baseline characteristics were balanced between the treatment groups

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Study MI-CP111Follow-up of Subjects

TIV

N=4232

FluMist

N=4243

Median duration of follow-up, days (range) 219 (0-224) 219 (0-224)

2 Dose group who received Dose 2 94.3% 92.8%

Nasal swabs collected (per child) 10,335 (2.4) 10,142 (2.4)

Of cultures taken, proportion within 24 hours of symptoms

87% 85%

ITT Population

Follow-up was also balanced between the treatment groups

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Study MI-CP111Influenza Strains in the General Population, 2004-2005

Proportion of Strains

Subtype Strain U.S. Europe

A/H1N1 A/New Caledonia/20/99-like 1% 19%

A/H3N2A/Wyoming/3/2003-like 15% 2%

A/California/7/2004-like 51% 59%

BB/Yamagata/16/88 lineage* 25% 11%

B/Victoria/02/87 lineage 9% 8%

No strain-specific data available for AsiaMismatched strains shown in blue italics; *matched and mismatched B/Yamagata strains circulated

Source: U.S. Centers for Disease Control and Prevention, European Influenza Surveillance Scheme (EISS)

High proportion of mismatched A/H3N2 circulated as well as some mismatched B and alternate lineage B

23 C C C T T T

C C CC CC CCC C CC CCCCCC CCCCCC CC CCCCCCCC C CCC CC CCCCCCCCCCCCCCCCCCCCC CCCCCCC CCCC CCC CCCCCCCC CCCCCCCCCCCC CCCCCCCCCC CCCC

CCCCCCCCCCCCCCC CCCCCCCCCCCC CC CCC

CCCCCC CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCC CCC CCCCC C CCC C C CCCCCC CCCCCC CCCC CCCCCCCCCC CCCCCCCCCCCCCCCCCCCCCCC CCCCC

T T T T T TT TTTT TTTTT TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

TTT TTTTTTTTTTTTTTTTTTTTT

TTTTTTTTTTTTTT

TTTTTTTT

TTTTTT

TTTTTTT TT

TTTTTTTTTTTTTTTT

TTTTTTTTTTTTTTTT

TTTTTTTTTTT

TTTTTTTTTTTTTTTTT TTTTTTTTTTTTT TTT

TTTTTTTTTTTTTTTTTTTTTTTTTT TTTTTTTTTTTTTTT TTT TTTTTT TTT T TTTTTTT TTTTTTTTTTT TT

Culture-confirmed Modified CDC-ILI Caused by Any Wild-type Strain (Matched and Mismatched)

01 NOV 04 01 DEC 04 01 JAN 05 01 FEB 05 01 MAR 05 01 APR 05 01 MAY 05

Perc

ent

10.09.59.08.58.07.57.06.56.05.55.04.54.03.53.02.52.01.51.00.50.0

FluMist1st immunizationscompleted by 10/29/04

TIV

Study MI-CP111All Culture-Confirmed Modified CDC-ILI

338 cases

153 cases

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Study MI-CP111 Efficacy Comparison: Primary and Secondary Endpoints – ATP and ITT

TIV

FluMist

Comparative Efficacy Against Culture-confirmed Modified CDC-ILI

58.2%(P<0.001)

0.7

2.6

0

12

3

4

5

67

Matched Strains

Mismatched Strains

Matched Strains

Mismatched Strains

Att

ack

Ra

te (

%)

No. of Cases 9393 5353 102102245245 5555100100 111111

TIV N=4232, FluMist N=4243TIV N=4232, FluMist N=4243

ATP ITT

44.5%(P<0.001)

2.4

1.4

6.2

56.6%(P<0.001)

0.7

2.6

46.0%(P<0.001)

2.4

1.3

6.0

TIV N=3936, FluMist N=3916TIV N=3936, FluMist N=3916

255255

Solid bars = matched

Hatched bars = mismatched

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Study MI-CP111 Efficacy Comparison by Strain

TIV (N=3936)

FluMist (N=3916)

Comparative Efficacy Against Culture-confirmed Modified CDC-ILI (ATP Population)

54.9%(P<0.001)

89.2%(P<0.001)

79.2%(P<0.001) 16.1%

(P=NS)

8.6

0.7

4.5

3.53.9

0.1

0.9

2.9

0

12

3

4

5

67

89

All Strains H1N1 H3N2 B

Att

ack

Ra

te (

%)

Strain

No. of Cases 338338 153153 332727 3737178178 115115136136

10

Solid bars = matched

Hatched bars = mismatched

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Study MI-CP111 Efficacy Comparison by Age: Matched Strains

29.1%(P=NS)

52.5%(P<0.001)

1.7

2.9

1.3 1.4

0

12

3

4

5

67

89

6-23 mos

Att

ack

Ra

te (

%)

3232 2323

10

24-59 mos

6161 3030

Comparative Efficacy Against Culture-confirmed Modified CDC-ILI (ATP Population)

Age Group

No. of Cases

TIV N=1852, 6-23 mos N=2084, 24-59 mos

FluMist N=1834, 6-23 mos N=2082, 24-59 mos

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Study MI-CP111 Efficacy Comparison by Age: All Strains

55.7%(P<0.001)

54.4%(P<0.001)

7.2

9.8

3.2

4.5

0

12

3

4

5

67

89

6-23 mos

Att

ack

Ra

te (

%)

133133 5959

10

24-59 mos

205205 9494

TIV N=1852, 6-23 mos N=2084, 24-59 mos

FluMist N=1834, 6-23 mos N=2082, 24-59 mos

Age Group

No. of Cases

Solid bars = matchedHatched bars = mismatched

Comparative Efficacy Against Culture-confirmed Modified CDC-ILI (ATP Population)

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Study MI-CP111Other Efficacy Endpoints

Illness associated with a positive culture for all strains regardless of match

45.9%(P=0.046)

0.5

0

12

3

4

5

67

Symptomatic Influenza

LRI AOM

Att

ack

Ra

te (

%)

No. of Cases 393393 195195 18183333 26265454

50.6%(P<0.001)

10.0

5.0

0.8

50.6%(P=0.003)

1.40.7

8

9

10TIV (N=3936)

FluMist (N=3916)

Solid bars = matchedHatched bars = mismatched

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Overall Efficacy ConclusionsChildren <5 Years of Age

High levels of efficacy against influenza Significantly higher efficacy compared to TIV in MI-CP111 Cross-protection against mismatched A/H3N2, including

better cross-protection compared to TIV in MI-CP111

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SafetyFluMist in Children <5 Years of Age

For children without a history of wheeze/asthma:Safety established in children 24-59 monthsRisk-benefit warrants availability for children 12-23 months

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FluMist Safety in Children <5 Years

Reactogenicity and Adverse Events Mortality Serious Adverse Events Wheezing Outcomes Risk-benefit Summary

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Study MI-CP111: Reactogenicity

Injection Site Reaction

Runny Nose/Nasal Congestion

Fever >100°F

Fever >101°F

Fever >102°F

TIV 25% 46% 12% 7% 4%

FluMist 21% 57% 15% 8% 4%

p<0.001 p<0.001 p<0.001 NS NS

Each child received both an intranasal spray and an intramuscular injection

Percent of Children with Events Days 0–10Two Dose Group, Post Dose 1

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Study MI-CP111Adverse Events (AE) Through 28 Days

Approximately 30% of children in both groups had >1 AE Adverse events with difference >1% between groups:

Events higher with FluMist: sneezing (1.1%) Events higher with TIV: diarrhea (1.1%), AOM (1.5%), and rash (1.3%)

Severe AE and related AE were balanced between treatment groups

A small number of children in each group did not receive a second vaccination because of an AE or RE 27/3247 (0.8%) TIV, 37/3269 (1.1%) FluMist

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2 deaths occurred on study, both were unrelated 1 FluMist: 1 year-old due to foreign body (toy) aspiration 1 TIV: 2 year-old due to a house fire

Study MI-CP111Mortality

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Overall SAE rates were similar: 3.1% TIV, 3.3% FluMist 94% of all SAEs were hospitalizations

Increased hospitalization rate with FluMist in 6-11 months

Study MI-CP111SAE/Hospitalizations Through 180 Days Post Last Dose

0%

2%

4%

6%

8%

10%

6-11 12-23 24-35 36-47 48-59

Age (mos)

Incid

en

ce

TIV

FluMist

Hospitalization Rates by Age

For all subjects

p=0.002

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Overall SAE rates were similar: 3.1% TIV, 3.3% FluMist 94% of all SAEs were hospitalizations

Increased hospitalization rate with FluMist in 6-11 months

Study MI-CP111SAE/Hospitalizations Through 180 Days Post Last Dose

0

1

2

3

4

5

6

7

8

9

10

6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24Month of Age

Per

cen

tag

e o

f Su

bje

cts

with

Ho

spita

lizat

ion TIV

FluMist

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Study MI-CP111Hospitalizations in Children 6-11 Months of Age

TIV FluMist

Lower Respiratory 7 18

Upper Respiratory 3 7

Gastrointestinal 8 13

Other Infectious 2 7

Other 1 6

Total 21 51

0 50 100 150 200 250 300

FluMist

TIV

Days Following Randomization

Temporal Distribution of HospitalizationsHospitalization by Diagnosis

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Study MI-CP111Additional Exploratory Safety Analysis

Multiple additional factors were evaluated for association with safety parameters

Prior history of wheeze/asthma was prospectively collected and identified by either parent or investigator 21% of children had a history of wheeze/asthma reported

85% by parent15% by health care provider only

Prior history of wheeze/asthma was associated with higher rates of hospitalization

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Study MI-CP111Hospitalization by Age and History of Wheeze/Asthma, Through 180 Days Post Last Dose

0%

1%

2%

3%

4%

5%

6%

7%

8%

9%

10%

6-11 12-23 24-35 36-47 48-59

Age (mos)

Inci

den

ce

TIV

FluMist

Without a history of wheezing (N=6580)

p=0.004

0%

1%

2%

3%

4%

5%

6%

7%

8%

9%

10%

6-11 12-23 24-35 36-47 48-59

Age (mos)

Inci

den

ce

TIV

FluMist

With a history of wheezing (N=1772)

p=0.039

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Further evaluation is needed in children 6-11 months of age

12-59 months of age with a history of wheeze/asthma

No SAE/hospitalization increase in children 12-59 months of age without a history of wheeze/asthma

Study MI-CP111SAE/Hospitalization Conclusions

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Protocol-defined Medically Significant Wheezing (MSW) Wheeze on physical examination plus at least one of the following: new

daily bronchodilator use, respiratory distress or hypoxemia Parents instructed to have child evaluated by HCP for any respiratory

illness including wheezing Treatment left to physician discretion

Any wheeze Not a pre-specified case definition in the protocol Any wheeze event reported by parent or investigator Includes MSW and other wheeze events

Study MI-CP111Wheezing Outcomes

Pre-specified interval: randomization through 42 days post last dose

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Study MI-CP111Wheezing Outcomes Through 42 Days Post Last Dose

0%

2%

4%

6%

8%

10%

12%

14%

16%

18%

20%

Protocol DefinedWheeze (MSW)

Any Wheeze

Incid

en

ce

TIV

FluMist

0%

2%

4%

6%

8%

10%

12%

14%

16%

18%

20%

Protocol DefinedWheeze (MSW)

Any Wheeze

Incid

en

ce

TIV

FluMist

Children 24-59 MonthsChildren 6-23 Months

p=0.002

For all subjects regardless of history of wheeze/asthma

p=0.002

Wheezing increased in children 6-23 months of age

No increase in children 24-59 months of age

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Study MI-CP111Protocol-Defined Wheezing (MSW) within 42 Days Post Last Dose By Age at Study Entry

Higher rates of wheezing in FluMist recipients through 23 months of age

0

2

4

6

8

10

12

14

16

18

20

6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59

Month of Age

Per

cen

tag

e o

f S

ub

ject

s w

ith

MS

W

TIV

FluMist

Protocol-Defined Wheezing (MSW) Rates by Age

6-23 Months 24-59 Months

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Study MI-CP111Severity of MSW* in Children <24 Months

MSW occurred in 192 children 75 TIV, 117 FluMist

14 children were hospitalized for MSW 4/75 TIV vs. 10/117 FluMist

3 in each group had a pathogen identified No ICU admission or mechanical ventilation because of MSW

69% of TIV cases and 75% of FluMist cases had new daily bronchodilator use but no respiratory distress or hypoxemia

Rates of recurrent wheezing through 180 days post last dose At least 1 additional episode: 21/75 (28%) TIV vs. 38/117 (32%) FluMist At least 2 additional episodes: 4/75 (5%) TIV vs. 5/117 (4%) FluMist

* Protocol-defined (MSW) within 42 days after last vaccination

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Study MI-CP111Severity of MSW* in Children 12-23 Months Without a History of Wheeze/Asthma

MSW occurred in 58 children 23 TIV, 35 FluMist

3 children were hospitalized for wheezing 1/23 TIV, 2/35 FluMist

1 in each group had a pathogen identified

74% of TIV cases and 86% of FluMist cases had new daily bronchodilator use but no respiratory distress or hypoxemia

Rates of recurrent wheezing through 180 days post last dose At least 1 additional episode: 5/23 (22%) TIV vs. 5/35 (14%) FluMist At least 2 additional episodes: 1/23 (4%) TIV vs. 1/35 (3%) FluMist

* Protocol-defined (MSW) within 42 days after last vaccination

46

Wheezing is not increased in children >24 months of age

There appears to be an increase in wheezing in children 12-23 months of age without a prior history of wheeze/asthma

Study MI-CP111Wheezing Conclusions

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Study MI-CP111Risk-Benefit Summary

Assess overall risks/benefits of FluMist relative to TIV Data display:

Rate differences (FluMist-TIV) per 1000 children Safety endpoints from randomization through 42 & 180 days after last

vaccination Culture-confirmed modified CDC-ILI from randomization through 180

days after last vaccination based on all cases (matched and mismatched)

Summaries for 12-23 months and 24-59 months without a history of wheeze/asthma

48

Study MI-CP111 Event Rate Differences (FluMist-TIV) per 1000 Children with 95% CI in Children Without a History of Wheeze/Asthma

Benefit

Risk

FluMist N=1615, TIV N=1625

24-59 Months12-23 Months

FluMist N=1053, TIV N=1060

-8

7 4

-35

-3

1218

-100

-50

0

50

100Any

wheezeMSW Hosp Any

wheezeMSW Hosp mCDC-

ILI

Through42 Days PLD

Through180 Days PLD

-8-3

1

-6

-49

-6-8

Anywheeze

MSW Hosp Anywheeze

MSW Hosp mCDC-ILI

Through42 Days PLD

Through180 Days PLD

-100

-50

0

50

100

Wheeze endpoints Hospitalization Culture-Confirmed Modified CDC-ILI

49

Safety Summary Reactogenicity of FluMist as expected Further evaluation is needed in children

6-11 months of age 12-59 months of age with a history of wheeze/asthma

Based on risk-benefit profile for the 77% of children in MI-CP111 who were 12-59 months without a history of wheeze/asthma For children 24-59 months, significant benefit and no increase in wheezing

or hospitalization For children 12-23 months, significant benefit but there appears to be a

residual increase in wheeze within 42 days post-vaccination

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Proposed Post-marketing Initiatives

Proposed observational safety study in children 12-59 months of age

Similar to ongoing post-marketing safety study in healthy children and adults 5-49 years of age

Planned enrollment of at least 20,000 FluMist recipients Including assessment of hospitalizations and wheezing

Passive surveillance Education & outreach

Risks included in package insert Appropriate language in FluMist Vaccine Information Statement (VIS) Targeted outreach to healthcare practitioners and to parents/guardians

of children vaccinated with FluMist

51

Overall ConclusionsChildren <5 Years of Age

Influenza causes significant morbidity in children on an annual basis Influenza vaccine options are limited for young children FluMist represents a highly efficacious vaccine in children <5 years

73 to 93% efficacy in placebo-controlled studies 55% fewer cases of influenza illness than TIV in MI-CP111 Significant cross-protection against mismatched A/H3N2, including better

cross-protection compared to TIV Safety of FluMist established in children 24-59 months without a history

of wheeze/asthma FluMist risk-benefit profile in children 12-23 months without a history of

wheeze/asthma also warrants vaccine licensing in this population

52