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

2. 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. 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)
These slides have been provided by Pfizer to HCPs for the purposes of medical education 3

4. PREVENAR13 – Moving towards the Adult Franchise
November 16, 2011
Prevenar13 : US-FDA considers ‘protection of adults/elderly from IPD and non-bacteremic pneumococcal pneumonia to be a meaningful therapeutic benefit’over existing treatments‘1
22 September 2011
Prevenar13: Active immunization for the prevention of IPD caused by Streptococcus pneumoniae in adults aged 50 years and older.2
To date, over 50 nations have approved Prevenar 13 adult use - Thailand, Australia, Bolivia, Philippines and a host of European countries among them3
1. accessed on December 20, 2011
2. Summaries of positive opinion 22 September EMA/CHMP/763049/2011 accessed December 20, 2011
3. accessed Nov 20, 2011

5. Prevenar13 - Countries shifting back1
*Notably, the number of childhood IPD caused by serotype 3 has increased from one case in 2009 to six cases in 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% respectively in ,2
Hong Kong
December 5, 2011
The Northern Territory has notified around 2 cases of invasive pneumococcal disease caused by type 3, 6A and 19A per year in under 2 years old over the last 3 years.3
Australia
OCTOBER 1, 2011
1. SCVPD. 2.
3.MEMORANDUM, Department of Health, Australia, 30/08/2011, p.1 (Ref no.DF 2011/3616)

6. Prevenar13 - Countries shifting back2
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 19A, not contained in either the 7-valent or the 10-valent vaccine.1
Canada
November 17, 2010

7. The Real Life Experience
PREVENAR13
The Real Life Experience

8. ABC surveillance: early trends for  reduction of IPD in children <2 years after Prevenar13 introduction
USA
IPD
3 + 1
PCV13 in April 2010
PCV13
Incidence of IPD in children <2 years between 20062008 and 2010 (n=14,168)
All serotypes
PCV13 serotypes
Incidence (cases per 100,00)
*p<0.0001 *
PCV13 introduced
PCV13 introduced
*p<0.0001 *
References:
Moore M et al. ICAAC Annual Meeting Presentation #G Abstract available at: [accessed October 2011]
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
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 20062008 (2009, year of influenza pandemic, was excluded) .
These slides have been provided by Pfizer to HCPs for the purposes of medical education
Moore M et al. ICAAC Annual Meeting Presentation #G1-538

9. Serotyped IPD isolates (1 July 2007 to 30 June 2011)
USA
IPD
Multi-hospital study: early trends for reduction of IPD in children (all ages) after PCV13 introduction
3 + 1
PCV13 in April 2010
PCV13
Serotyped IPD isolates (1 July 2007 to 30 June 2011)
All isolates
Isolates by serotype
PCV13 introduced
Serotype 19A 45% in 20102011
36%
References:
Kaplan SL et al. IDSA Annual Meeting Presentation #LB-1. Abstract available at: . [accessed October 2011].
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
Hospital-based observational study. Children (all ages) with IPD prospectively identified from 8 children’s hospitals in the US since IPD confirmed by a central laboratory. Serotype and antibiotic resistance were identified.
These slides have been provided by Pfizer to HCPs for the purposes of medical education
Kaplan SL et al. IDSA Annual Meeting Presentation #LB-1. 9

10. PCV National Programs
PCV7 / PCV13
PCV13 / PCV10 *
PCV10

11. USA
IPD
Alaska: reduction of IPD cases in children <5 years after Prevenar13 introduction
3 + 1
PCV13 in April 2010
PCV13
IPD occurrence in children <5 years
Alaskan Native children
Non-Alaskan Native children
P=0.003
P=0.01
P=0.5
Incidence rate per 100,000
71%
100%
References:
Bruce M et al. IDSA Annual Meeting Poster #656. Abstract available at: . [accessed October 2011]
P=0.02
P=0.004
P=0.9 [NS]
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 Vaccine coverage in April 2011 was 90%, including 2,551 children who were vaccinated during the period AprDec 2010.
These slides have been provided by Pfizer to HCPs for the purposes of medical education
Bruce M et al. IDSA Annual Meeting Poster #656.

12. Ohio: reduction in overall IPD, all ages
USA
IPD
3 + 1
PCV13 in April 2010
PCV13
IPD incidence (all serotypes, 19A highlighted)
Many of the strains between 2003 and 2009 (43.449.1%) 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
PCV7
PCV13
References:
Jacobs MR et al. ICAAC Annual Meeting Presentation #G Abstract available at: [accessed October 2011].
Observational study. Isolates were sequentially collected. S. pneumoniae isolated in the clinical microbiology laboratory, 19992010. Serotyping was performed by capsular swelling using commercial antisera.
These slides have been provided by Pfizer to HCPs for the purposes of medical education
Jacobs MR et al. ICAAC Annual Meeting Presentation #G3-773.

13. Six additional serotypes in Prevenar 13 but not in PCV7
UK: early trend for reduction of IPD in children <2 years after Prevenar13 introduction UK
IPD
2 + 1
PCV13 in 2010
PCV13
Cumulative weekly number of IPD reports in children <2 Years in England and Wales by epidemiological year
PCV7 serotypes
Six additional serotypes in Prevenar 13 but not in PCV7
References:
[accessed 18th November 2011].
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.
These slides have been provided by Pfizer to HCPs for the purposes of medical education
. Accessed 18th November 2011.

14. UK
IPD
Significant reduction of IPD caused by additional Prevenar13 serotypes in children <2 years
2 + 1
PCV13 in 2010
PCV13
1, 3, 5, 6A, 6C combined
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 7F
References:
Miller E et al. Vaccine 2011 Oct 5. ePub ahead of print.
19A
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.
These slides have been provided by Pfizer to HCPs for the purposes of medical education
Miller E et al. Vaccine 2011 Oct 5. ePub ahead of print.

15. Reduction in IPD caused by additional serotypes contained in PCV10 and Prevenar13 in children <2 years
GER
IPD
3 + 1
PCV13 in Dec PCV10 in Apr 2009
PCV13
Cumulative number of 6 additional PCV13 serotypes isolated from children <2 years with IPD
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
References:
Van der Linden M et al. ICAAC Annual Meeting Presentation #G Abstract available at: [accessed October 2011]
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 Surveillance was passive and taken from diagnostic laboratories located nationwide.
These slides have been provided by Pfizer to HCPs for the purposes of medical education
PCV10 & PCV 13 are currently available in Germany
Introduction of PCV10 in April 2009 & PCV13 in Dec 2009.
Van der Linden M et al. ICAAC Annual Meeting Presentation #G3-775.

16. PCV13
Pneumonia
Reduction in Hospitalization Rates for Pneumonia with Prevenar13 in children < 2 years
Hospitalization Rates for Bacterial Pneumonia
in Children < 2 years of age
Hospitalization Rates for Pneumococcal Empyema In Children < 2 years of age
PCV 7
PCV 7
PCV 13
PCV 13
2010 vs
79.0%
47.4%
WHO defined Radiological Pneumonia:
↓ post PCV13 introduction
Pirez MC et al. SLIPE, May 2011, Punta Cana, Dominican Republic

17. NPC rates (%); children
Significant reduction of NP carriage of 6 additional Prevenar13 serotypes in children <1 year
USA
NPC
3 + 1
PCV13 in April 2010
PCV13
NPC rates (%); children
p=0.002
p=NS
Age <12 months
Decline in vaccine-type carriage prevalence observed for the 6 additional vaccine serotypes in children <12 months, but not in children 1259 months
Age 1259 months
References:
Hsu K et al. IDSA Annual Meeting Poster #666. Abstract available at: [Accessed October 2011]
This study was conducted in children < 5 yo.
SP was recovered from 212 (22.9%).  Between 2007 and 2011, in children < 12 months of age, pneumococcal carriage prevalence was comparable (21.7 per 100 vs per 100), however overall carriage of a PCV 13 serotypes (1, 3, 5, 6A, 7F, 19A) declined in 2011 from 7.3/100 to 1.3/ 100 [P=0.002]. In children 12 though 59 months of age, pneumococcal carriage increased in 2011 from 23.8/100 to 30.2/100 (P=0.01) but no difference in carriage of the 6 additional serotypes in PCV13 was observed (4.4/100 vs 4.9/100). A reduction in carriage prevalence of serotypes 6A and 7F (P=0.06 and 0.12 respectively) was observed in children 0 through 59 months of age but no change in carriage of 19A is evident to date.
A non-statistically significant decline in carriage of serotypes 6A and 7F in children 0 through 59 months, was observed. But no change in 19A carriage for children 0-59 mo found
p=0.01
p=NS
Observational 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.
These slides have been provided by Pfizer to HCPs for the purposes of medical education
Hsu K et al. IDSA Annual Meeting Abstract. #666 17

18. Early, widespread evidence of a positive PCV13 impact at a global level
IPD: Alaska, USA
IPD: ABC, USA
IPD: HPA, UK
Pneumonia: Uruguay
IPD: Germany
IPD: USA
Carriage: France
IPD: Ohio, USA
Carriage: Boston, USA
Early evidence needs to be confirmed by continuous surveillance
These slides have been provided by Pfizer to HCPs for the purposes of medical education

19. PREVENAR
The India PMS Study

20. PREVENAR PMS INDIA Study Objective Study Design
To collect safety and tolerance data on PREVENAR for primary immunization and catch-up population
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

21. PREVENAR PMS INDIA Inclusion Criteria 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 months of age

22. PREVENAR PMS INDIA 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

23. PREVENAR PMS INDIA 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
* Minimum 4 week separation between vaccine administrations
Catch-up Immunization Schedule:
Dose 2
Dose 3
From 12 – 23 months of age
Concomitant vaccine administration allowed in other extremity

24. PREVENAR PMS INDIA 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

25. PREVENAR PMS INDIA
Demographics

26. PREVENAR PMS INDIA

27. Total Incidences of Adverse Events
PREVENAR PMS INDIA
Total Incidences of Adverse Events
Primary
Catch Up
Total

28. Adverse Events: Primary Series & Catch up
PREVENAR PMS INDIA
Adverse Events: Primary Series & Catch up
Dose 1
Dose 2
Dose 3
Catch Up

29. Injection Site Adverse Events
PREVENAR PMS INDIA
Injection Site Adverse Events

30. PREVENAR PMS INDIA Completion Status 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)
Others (N, %)
1 (12.5)
Data represented as [N, (%)]

31. PREVENAR PMS INDIA Summary
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
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
Black S, et al Pediatr Infect Dis J 2000; 19(3):

32. Prevenar: Taking Pride in Healthy Babies
PREVENAR PMS INDIA
Prevenar: Taking Pride in Healthy Babies
Publication

33. MERRY XMAS & A HAPPY NEW YEAR 2012