1 PREVENAR13 24 st December 2011 Dr. Gautam Rambhad Associate Director Medical Services Emerging New Data & PMS India Report On PCV7

1

PREVENAR13

24st December 2011

Dr. Gautam RambhadAssociate Director Medical Services

Emerging New Data&

PMS India Report On PCV7

22

JOURNEY OF PREVENAR IN INDIA

Prevenar (PCV7) was launched in June 2006 DCGI – Request to conduct PMS study Prevenar13

India launch - July 2010

Approved in 115 countries*

Launched in 106 countries*

* As of Dec 2011

3

These slides have been provided by Pfizer to

HCPs for the purposes of medical

education3

Extensive experience with PCV7

IPD • USA: 76% decrease in overall IPD (<5 years)• USA: 100% decrease in vaccine-type IPD (<5 years)• UK: 98% decrease in vaccine-type IPD (<2 years)• Germany: 90% decrease in vaccine-type IPD (<2 years)• Norway: 95% decrease of vaccine-type IPD (<5 years)• Ireland: 84% decrease in vaccine-type IPD (<2 years)• Belgium: 97% decrease in vaccine-type IPD (<5 years)• Netherlands: 90% decrease in vaccine-type IPD (<2 years)

Pneumonia • USA: 22% reduction in all-cause CAP hospitalizations (<1 year)• USA: 39% reduction in all-cause CAP hospitalizations (<2 years)• USA: 52% reduction in all-cause CAP hospitalizations (<2 years)• UK: 22% reduction in empyema-related hospitalization (<15 years) • Italy: 15.2% reduction in all-cause CAP hospitalizations (<2 years)

AOM • Greece: 48% reduction in pneumococcal AOM visits (<14 years)• Greece: 38% reduction in overall AOM episodes (<14 years)• USA: 42.7% reduction in ambulatory visits for AOM (<2 years)• Sweden: 26% reduction in AOM episodes (<2 years) • Italy: 36.4% reduction in vaccine-type AOM hospitalizations (<2 years)

NP carriage • Netherlands: 92% reduction in vaccine-type carriage (at 24 months)• UK: 69% reduction in vaccine-type carriage (<4 years)

4

22 September 201122 September 2011Prevenar13: Active immunization for the prevention of IPD caused by Streptococcus pneumoniae in adults aged 50 years and older.2

November 16, 2011November 16, 2011Prevenar13 : US-FDA considers ‘protection of adults/elderly from IPD and non-bacteremic pneumococcal pneumonia to be a meaningful therapeutic benefit’over existing treatments‘1

1. http://www.medscape.com/viewarticle/753734_print accessed on December 20, 20112. Summaries of positive opinion 22 September 2011 EMA/CHMP/763049/2011 accessed December 20, 20113. http://www.pharmaceutical-int.com/news/fda-panel-approves-prevnar-13-adult-use.html accessed Nov 20, 2011

PREVENAR13 – Moving towards the Adult Franchise PREVENAR13 – Moving towards the Adult Franchise

To date, over 50 nations have approved Prevenar 13 adult use - Thailand, Australia, Bolivia, Philippines and a host of European countries among them3

5

Prevenar13 - Countries shifting back1

*Notably, the number of childhood IPD caused by serotype 3serotype 3 has increased from one case in 2009 to six cases in 2010. Consequently, among children below 5 years of age, the proportion of IPD caused by serotypes covered by PCV7*, PCV10* and PCV13 were 70%, 70% and 100% in 2009 changed to 47%, 47% and 93%47%, 47% and 93% respectively in 2010.1,2

Hong KongHong KongDecember 5, 2011

The Northern Territory has notified around 2 cases of invasive pneumococcal disease caused by type 3, 6A and 19A3, 6A and 19A per year in under 2 years old over the last 3 years.3

AustraliaAustraliaOCTOBER 1, 2011

1. SCVPD. http://www.chp.gov.hk/files/pdf/recommendations_on_the_use_of_13valent_pneumococcal_conjugate_vaccine_in_cip.pdf

2. http://www.chp.gov.hk/en/view_content/24122.html

3.MEMORANDUM, Department of Health, Australia, 30/08/2011, p.1 (Ref no.DF 2011/3616)

6

Recently, both Ontario and Quebec announced they would publicly fund Prevenar13 as part of the childhood immunization program, largely because it protects against additional serotypes, notably 19A19A, not contained in either the 7-valent or the 10-valent vaccine.1

CanadaCanadaNovember 17, 2010

Prevenar13 - Countries shifting back2

7

PREVENAR13

The Real Life Experience

8



education8

ABC surveillance: early trends for reduction of IPD in children <2 years after Prevenar13 introduction

Moore M et al. ICAAC Annual Meeting 2011. Presentation #G1-538

0

10

20

30

40

50

60

Jan-Mar Apr-Jun Jul-Sep Oct-Dec

2006-2008 2010

All serotypes PCV13 serotypes

*p<0.0001

*

IPD cases (isolation of pneumococcus from sterile sites) were identified through 10 Active Bacterial Core surveillance (ABCs) sites. Isolates were serotyped to identify those included in PCV13. Quarterly incidence of IPD (cases per 100,000) in 2010 was compared to 20062008 (2009, year of influenza pandemic, was excluded) .

Incidence of IPD in children <2 years between 20062008 and 2010 (n=14,168)

Among children <2 years old, rates of overall- and PCV13-serotype-related IPD were lower only in the fourth quarter of 2010

No significant changes were identified in IPD rates among other age groups

3 + 1

PCV13 in April 2010

USA

PCV13 introduced

PCV13 introduced

PC

V13

IPD

0

10

20

30

40

50

60


Inci

de

nce

(ca

ses

pe

r 1

00

,00

)

*p<0.0001

*

9



education9

Multi-hospital study: early trends for reduction of IPD in children (all ages) after PCV13 introduction

Serotyped IPD isolates (1 July 2007 to 30 June 2011)

0

10

20

30

40

50

60

70

80

90

19A 7F 3 6C 33FSerotype

No

of

iso

late

s

(in

va

siv

e p

ne

um

oc

oc

ca

l in

fec

tio

ns

)

2007-2008

2008-2009

2009-2010

2010-2011

Kaplan SL et al. IDSA Annual Meeting 2011. Presentation #LB-1.

Serotype 19A45% in 20102011

0

50

100

150

200

250

2007-8 2008-9 2009-10 2010-11

No

. o

f is

ola

tes

Total isolates

36%

Isolates by serotypeAll isolates

Hospital-based observational study. Children (all ages) with IPD prospectively identified from 8 children’s hospitals in the US since 1993. IPD confirmed by a central laboratory. Serotype and antibiotic resistance were identified.

Early trends indicate 36% reduction in IPD cases among 8 children's hospitals for the 12 months starting 4 months after the introduction of PCV13

19A cases decreased by 45% in the same period

3 + 1

PCV13 in April 2010

USA

PCV13 introduced

PC

V13

IPD

11



education11

Alaska: reduction of IPD cases in children <5 years after Prevenar13 introduction

IPD occurrence in children <5 yearsAlaskan Native children Non-Alaskan Native children

0

20

40

60

80

100

120

140

160

All serotypes PCV13serotypes

Non-PCV13serotypes

April 2006-March 2009 (Pre-PCV13)

April 2010-March 2011 (Post-PCV13)*

P=0.02 P=0.004 P=0.9 [NS]

Bruce M et al. IDSA Annual Meeting 2011. Poster #656.

0

20

40

60

80

100

120

140

160


Non-PCV13serotypes


April 2010-March 2011 (Post-PCV13)*

P=0.003 P=0.01 P=0.5

Inci

denc

e ra

te p

er 1

00,0

00

71%

100%

A decrease was noted in non-PCV13 disease among Alaska native children

State-wide birth cohort study involving the population of children <5. Pneumococcal isolates obtained from sterile sites and reported to Alaska-wide laboratory based surveillance sites. *April 2009–March 2010 was excluded because PCV13 was introduced pre-licensure in one high-risk region in 2009. Vaccine coverage in April 2011 was 90%, including 2,551 children who were vaccinated during the period AprDec 2010.

3 + 1

PCV13 in April 2010

USA

PC

V13

IPD

12



education12Jacobs MR et al. ICAAC Annual Meeting 2011. Presentation #G3-773.

Ohio: reduction in overall IPD, all ages

Observational study. Isolates were sequentially collected. S. pneumoniae isolated in the clinical microbiology laboratory, 19992010. Serotyping was performed by capsular swelling using commercial antisera.

0

50

100

150

200

250

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

No

. of

iso

late

s

Other

19A

IPD incidence (all serotypes, 19A highlighted)

PCV13PCV7• Many of the strains between 2003

and 2009 (43.449.1%) have been from the 6 additional serotypes now included in PCV13

• Most of these being serotype 19A, followed by serotypes 3 and 7F

• Although PCV13 was introduced only very recently, there has been a dramatic decrease in 2010 in the number of pneumococci isolated overall and in the proportion of serotype19A strains

3 + 1

PCV13 in April 2010

USA

PC

V13

IPD

13



education13

http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/Pneumococcal/EpidemiologicalDataPneumococcal/CurrentEpidemiologyPneumococcal/InPrevenar7/ . Accessed 18th November 2011.

Cumulative weekly number of IPD reports in children <2 Years in England and Wales by epidemiological year

Six additional serotypes in Prevenar 13 but not in PCV7PCV7 serotypes

UK: early trend for reduction of IPD in children <2 years after Prevenar13 introduction

2 + 1

PCV13 in 2010

UK

One year after PCV13 introduced in children <2 years: Maintained reduction of PCV7 types IPD Decreased number of reported cases of IPD related to 6 additional types included in PCV13 (particularly 19A

and 7F types)

Note: The above graph is based on week of isolation, therefore numbers for most recent weeks may not be complete. Numbers of reports of serotyped cases shown in the graph are not adjusted to account for any change that may have occurred over time and between age groups in the proportion of all IPD cases that are serotyped. The 7-valent conjugate vaccine was introduced into the childhood immunization schedule on the 4 September 2006, which corresponds with week 36 above.

PC

V13

IPD

14



education14

Significant reduction of IPD caused by additional Prevenar13 serotypes in children <2 years

Within one year of PCV13 introduction, IPD cases in children <2 years due to additional PCV13 serotypes were halved

Significant reduction of 7F and 19A reported IPD cases

2 + 1

PCV13 in 2010

Miller E et al. Vaccine 2011 Oct 5. ePub ahead of print.

7F

19A

UK

Study population: children who were eligible for PCV13 (one or more doses) who reported to the Health Protection Agency with IPD (n=235) and had a complete vaccine history taken. IPD defined as isolation of S. pneumoniae from a normally sterile site. PCV13 was introduced nationally in week 13, 2010.

1, 3, 5, 6A, 6C

combined

PC

V13

IPD

15



education15

Reduction in IPD caused by additional serotypes contained in PCV10 and Prevenar13 in children <2 years

Van der Linden M et al. ICAAC Annual Meeting 2011. Presentation #G3-775.

PCV13 in Dec 2009

PCV10 in Apr 2009

3 + 1

Cumulative number of 6 additional PCV13 serotypes isolated from children <2 years with IPD

GER

National observational study. Data taken from the German National Reference Center for Streptococci (GNRCS) from children <16 years of age with confirmed IPD between 1997 and 2011. Surveillance was passive and taken from diagnostic laboratories located nationwide.

PCV10 & PCV 13 are currently available in GermanyIntroduction of PCV10 in April 2009 & PCV13 in Dec 2009.

One year after the introduction of higher valent PCVs first effects are visible, with less reported cases among children <2 years due to serotypes 1, 3, 6A and 7F

PC

V13

IPD

16

0

200

400

600

800

1000

1200

1400

1600

2005 2006 2007 2008 2009 2010 0

10

20

30

40

50

60

2005 2006 2007 2008 2009 2010

PCV 7

Reduction in Hospitalization Rates for Pneumonia with Prevenar13 in children < 2 years

79.0% 47.4%

PCV 13

PCV 7PCV 13

Pirez MC et al. SLIPE, May 2011, Punta Cana, Dominican Republic

Hospitalization Rates for Bacterial Pneumonia in Children < 2 years of age

Hospitalization Rates for Pneumococcal Empyema In Children < 2 years of age

2010 vs. 2005-2007

WHO defined Radiological Pneumonia: ↓ post PCV13 introduction

Pne

umo

nia

PC

V13

17



education17

0%

10%

20%

30%

40%

S. Pneumoniae carriage Additional 6 PCV13 serotypecarriage

2006/2007

2010/2011

NPC rates (%); children

Age 1259 months

Significant reduction of NP carriage of 6 additional Prevenar13 serotypes in children <1 year

Hsu K et al. IDSA Annual Meeting 2011. Abstract. #666

p=0.01

p=NSObservational study. Nasopharyngeal surveillance was performed in children <60 months of age attending the primary care center (PCC) at Boston Medical Center. NP cultures were collected after obtaining informed consent and processed by routine microbiologic methods.

Decline in vaccine-type carriage prevalence observed for the 6 additional vaccine serotypes in children <12 months, but not in children 1259 months

NP

C

3 + 1

PCV13 in April 2010

USA

PC

V13

0%

5%

10%

15%

20%

25%


2006/2007

2010/2011

p=0.002

p=NS Age <12 months

18



education18

Early, widespread evidence of a positive PCV13 impact at a global level

0

50

100

150

200

250

2007-8 2008-9 2009-10 2010-11

No

. of

iso

late

s

Total isolates

IPD: USA

PC

V13

IPD: ABC, USA

0

10

20

30

40

50

60


Inc

ide

nce

(ca

ses

per

10

0,0

0)

*p<0.0001

*

0

10

20

30

40

50

60


Inc

ide

nce

(ca

ses

per

10

0,0

0)

*p<0.0001

*

IPD: Alaska, USA

0

20

40

60

80

100

120

140

160


Non-PCV13serotypes


April 2010-March2011 (Post-PCV13)*

P=0.003 P=0.01 P=0.5

Inci

de

nce

ra

te p

er 1

00,

000

0

20

40

60

80

100

120

140

160


Non-PCV13serotypes


April 2010-March2011 (Post-PCV13)*

P=0.003 P=0.01 P=0.5

Inci

de

nce

ra

te p

er 1

00,

000

IPD: Ohio, USA

0

50

100

150

200

250

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

No

. of

iso

late

s

Other

19A

0

50

100

150

200

250

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

No

. of

iso

late

s

Other

19ACarriage: Boston, USA

0%

5%

10%

15%

20%

25%


2006/2007

2010/2011

p=0.002

p=NS Age <12 months

0%

5%

10%

15%

20%

25%


2006/2007

2010/2011

p=0.002

p=NS Age <12 months

IPD: Germany

Carriage: France

9

6.8

0.5 0.5 01.2

0

19.4

14.4

2.5

0 0

2.5

00

5

10

15

20

25

6 addPCV13 STs

19A 7F 6A 5 3 1

Pe

rce

nta

ge

of

iso

late

s (

%)

PCV13 vaccinated (N=652)

non PCV13 vaccinated (N=290)

P<0.001

P<0.001

P=0.01

9

6.8

0.5 0.5 01.2

0

19.4

14.4

2.5

0 0

2.5

00

5

10

15

20

25

6 addPCV13 STs

19A 7F 6A 5 3 1

Pe

rce

nta

ge

of

iso

late

s (

%)

PCV13 vaccinated (N=652)

non PCV13 vaccinated (N=290)

P<0.001

P<0.001

P=0.01

IPD: HPA, UK

0

200

400

600

800

1000

1200

1400

1600

2005 2006 2007 2008 2009 2010

Pneumonia: Uruguay

Early evidence needs to be confirmed by continuous surveillance

19

PREVENAR

The India PMS Study

2020

Study Objective To collect safety and tolerance data on PREVENAR for

primary immunization and catch-up population

PREVENAR PMS INDIA

Study Design Open-label, multi-center, non-comparative, prospective

phase IV post-marketing observational study

A total of 161 investigators recruited 1094 children into the study

2121

Inclusion Criteria

For Primary Immunization Schedule:

Healthy male or female subjects 6 weeks + 5 days of age with no previous PREVENAR vaccination

For Catch-up Immunization Schedule:

Healthy male or female subjects 12-23 months of age

PREVENAR PMS INDIA

Inclusion Criteria

2222

Exclusion Criteria Known or suspected history of Streptococcus pneumoniae disease Previous anaphylactic or other severe vaccine-associated adverse

event Known or suspected impairment of immune system (including HIV

infection) Recipient of immunosuppressive agents or those with a major

congenital, developmental or serious chronic disorder Confirmed or suspected underlying evolving neurological disorder

or history of seizures History of thrombocytopenia or any coagulation disorder Acute illness at the time of vaccine administration

PREVENAR PMS INDIA

2323

Study Procedure

Primary Immunization Schedule: Dose 1(6 weeks +5 days)

Dose 2*(10 weeks + 5 days)

Dose 3*(14 weeks + 5 days)

6 weeks onwards X X X

* Minimum 4 week separation between vaccine administrations

Catch-up Immunization Schedule: Dose 1 Dose 2 Dose 3

From 12 – 23 months of age X

Concomitant vaccine administration allowed in other extremity

PREVENAR PMS INDIA

2424

Safety Evaluation Subject observed for 30 minutes post vaccination AE was documented in CRF and the subject followed

until all untoward reactions resolved Parents or guardians were advised to report local and/or

systemic events post-vaccination and report Serious AE reported within 24 hours to Medical

Department, Wyeth Limited

PREVENAR PMS INDIA

2525

Demographics 1094 ChildrenBoys (n=602; 55%)Girls (n=492;45%)

Primary(n=810)

Catch Up(n=284)

Boys(n=437)

54%

Girls(n=373)

46%

Boys(n=165)58.1%

Girls(n=119)41.9%

PREVENAR PMS INDIA

2626

Distribution of cases

South, n=383

East, n=46

North, n=451

West, n=214

PREVENAR PMS INDIA

2727

Total Incidences of Adverse Events

18.5

10.5

17.9

9.5

18.4

10.2

0

2

4

6

8

10

12

14

16

18

20

Per

cen

tag

e o

f su

bje

cts

with

AE

(%)

Children with AE Children with >1 AE

PrimaryPrimary TotalTotalCatch UpCatch Up

PREVENAR PMS INDIA

2828

Adverse Events: Primary Series & Catch up

60

73

51

66

47

56

25

22

0

10

20

30

40

50

60

70

80

Nu

mb

er

of

Ch

ildre

n

Lot Fussier than Usual Lot Sleepier than Usual Eating Poorly Warm to touch

Vomiting Diarrhoea Rash Redness

Hardness Swelling Pain

Dose 1Dose 1 Dose 2Dose 2 Dose 3Dose 3

Catch UpCatch Up

PREVENAR PMS INDIA

2929

Injection Site Adverse Events

0.90.5

0.7

2.1

3

2

0 0

0.50.2

0.1

1.1

9

8.2

7

7.7

0

2

4

6

8

10

12

14

Per

cen

tag

e o

f su

bje

cts

(%)

Redness Hardness Swelling PainPrimary - 1 Primary - 2 Primary - 3 Catch up

PREVENAR PMS INDIA

3030 Data represented as [N, (%)]

Primary(n=810)

Catch-up(n=284)

Dose 1 Dose 2 Dose 3

Children administered PREVENAR 810 804 803 284

No. of children who completed the study (N, %) 803 (99.13) 284 (100)

No. of early terminations from the study (N, %) 7 (0.86) 0 (0)

Reasons for Early Discontinuation

Lost to follow up (N, %)6 (87.5) 0 (0)

Others (N, %)1 (12.5) 1 (12.5)

Completion Status

PREVENAR PMS INDIA

3131

Most frequently reported AEs were pain/tenderness at injection site (9%) and fever (6.7%)

AEs were not clinically significant and are in line with previous data1

Lesser in incidence compared with AEs reported in Prevenar PI

Black S, et al Pediatr Infect Dis J 2000; 19(3): 187-195.

Summary

PREVENAR PMS INDIA

Other AEs noted (child lot fussier than usual, child lot sleepier than usual, child eating much more poorly than usual and injection site reactions) were transient, had < 2% incidence

Incidence of redness, swelling and a lump or hardness was much higher with concomitant vaccines compared to PREVENAR

The incidence of pain and tenderness at the injection site was higher in the PREVENAR group

32

Prevenar: Taking Pride in Healthy Babies

PREVENAR PMS INDIA

33

MERRY XMAS & A HAPPY NEW YEAR 2012

Documents

1 PREVENAR13 24 st December 2011 Dr. Gautam Rambhad Associate Director Medical Services Emerging New Data & PMS India Report On PCV7