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

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

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

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. http://www.medscape.com/viewarticle/753734_print accessed on December 20, 2011 2. Summaries of positive opinion 22 September 2011 EMA/CHMP/763049/2011 accessed December 20, 2011 3. http://www.pharmaceutical-int.com/news/fda-panel-approves-prevnar-13-adult-use.html accessed Nov 20, 2011

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 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% respectively in 2010.1,2 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. 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)

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

The Real Life Experience PREVENAR13 The Real Life Experience

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 2011. Presentation #G1-538. Abstract available at: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=6ffe8b06-3097-45ff-807e-3c59e8b9dee4&cKey=7566da3a-4114-4bc9-afdc-0f99d9548db3&mKey=0C918954-D607-46A7-8073-44F4B537A439. [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 2011. Presentation #G1-538

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 2011. Presentation #LB-1. Abstract available at: http://idsa.confex.com/idsa/2011/webprogram/Paper32831.html . [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 1993. 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 2011. Presentation #LB-1. 9

PCV National Programs PCV7 / PCV13 PCV13 / PCV10 * PCV10

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 2011. Poster #656. Abstract available at: http://idsa.confex.com/idsa/2011/webprogram/Paper32390.html . [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 2009. 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 2011. Poster #656.

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 2011. Presentation #G3-773. Abstract available at: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=81f099c8-52a2-4c3f-8724-e74cc93751a2&cKey=42f2bdb0-199d-442f-a786-d3b2df77b4eb&mKey=0C918954-D607-46A7-8073-44F4B537A439. [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 2011. Presentation #G3-773.

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

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.

Reduction in IPD caused by additional serotypes contained in PCV10 and Prevenar13 in children <2 years GER IPD 3 + 1 PCV13 in Dec 2009 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 2011. Presentation #G3-775. Abstract available at: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=81f099c8-52a2-4c3f-8724-e74cc93751a2&cKey=faaa232e-6402-4d20-bd13-f3edd0ffe52e&mKey=0C918954-D607-46A7-8073-44F4B537A439. [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 2011. 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 2011. Presentation #G3-775.

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. 2005-2007 79.0% 47.4% WHO defined Radiological Pneumonia: ↓ post PCV13 introduction Pirez MC et al. SLIPE, May 2011, Punta Cana, Dominican Republic

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 2011. Poster #666. Abstract available at: http://idsa.confex.com/idsa/2011/webprogram/Paper31981.html. [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. 23.2 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 2011. Abstract. #666 17

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

PREVENAR The India PMS Study

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

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 12-23 months of age

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

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

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

PREVENAR PMS INDIA Demographics

PREVENAR PMS INDIA

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

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

Injection Site Adverse Events PREVENAR PMS INDIA Injection Site Adverse Events

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, (%)]

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): 187-195.

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

MERRY XMAS & A HAPPY NEW YEAR 2012