1 Prevnar 13 for Adult Use (Age >50 Years) (Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM 197 Protein) Applicant: Wyeth Pharmaceuticals, Inc. Rosemary Tiernan, MD, MPH Division of Vaccines and Related Products Applications CBER/FDA Vaccines and Related Biological Products Advisory Committee Meeting November 16, 2011
2 Overview of Safety Presentation Studies Supporting Safety in Adults Age > 50 yrs Safety Population Safety Monitoring and Data Collection Adverse Reactions Summary/Conclusions
3 Six Phase 3 Studies Supported Safety of PCV13 in Adults StudySite Age (Yrs ) Schedule and ( # Vaccinated) 004 Naive USA Initial Study: Extension (3-4.5yrs): Cohort 1 PCV13 (417) PCV13/PCV13 (108) PCV13/23vPS (108) Cohort 1 23vPS (414) 23vPS/23vPS (189) Cohort 2 PCV13 (404) PCV13/PCV13 (214) 3000 >1 dose 23vPS > 3 yrs prior USA, GER Sweden > 68 1 dose of PCV13 (1049) 3001 Naive USA50-59 Group 1 PCV13 + TIV / Placebo ( ) Group 2 Placebo + TIV / PCV13 ( ) dose 23vPS > 5 yrs prior USA, Sweden > 70 Group 1 PCV13 (463) Year 0 Group 2 23vPS (473) Group 1.1 PCV13 / PCV13 (391) Year 1 Group vPS / PCV13 (404) 3008 Naive GER, NETH BELG, HUNG > 65 Group 1 PCV13 + TIV / Placebo ( ) Group 2 Placebo + TIV / PCV13 ( ) 3010 Naive USA60-64 Group 1 PCV13 (478 ) Year 0 Group 2 23vPS (237) Group 1.1 PCV 13 / PCV 13 (161) Year 1 Group 1.2 PCV13 / 23vPS (266) Group vPS/ PCV13 (223)
4 Six Phase 3 Studies Supported Safety of PCV13 in Adults Description of the Six Phase 3 Studies that Supported the Safety of Prevnar13 in Adults: –History of Prior PNEUMOVAX23 Vaccination –Study Site –Subject Age –Vaccine Schedule and –Number Vaccinated
5 Safety Population
6 Demographics Demographic Factors (N = 6198)PCV13 (N = 5667) Age (Years) (46.2) (11.4) (20.1) (13.4) > (8.9) Gender Female %* Race/Ethnicity White> 91% Black or African American % Hispanic or Latino % Asian % Native Hawaiian or other Pacific Islander <1% American Indian<1% Alaskan Native<1% Other<1.4% *Study 3005 Males ( %)
7 Demographics Demographics of Subjects (Across 6 Studies) and Specific Age Strata for Prevnar13 Recipients
8 Study Populations Pre-existing underlying diseases included if condition was “stable”: Disease not requiring significant change in therapy or hospitalization for worsening disease for 12 weeks before receipt of study vaccine Change to new therapy allowed if not caused by worsening disease Change in dose or therapy within category allowed Key Exclusion Criteria included: Receipt of diphtheria-tetanus toxoid containing vaccines within 6 months of study vaccine Streptococcus pneumoniae infection documented w/in past 5 years Impairment of immunological function: –Immunoglobulin deficiencies, hematological malignancies, known HIV infection, collagen vascular disorders and subjects receiving immunosuppressive therapy –If systemic corticosteroids administered short term for treatment of acute illness, subjects excluded from vaccination until corticosteroid therapy had been discontinued for at least 30 days. Serious chronic disorders: –Metastatic malignancy, severe chronic obstructive pulmonary disease, end-stage renal disease, clinically unstable cardiac disease, or any other disorder that in investigator’s opinion precluded subject from participating in study.
9 Underlying Medical Conditions in PCV13 Recipients (at 1 st Dose) Medical Conditions Vaccine NaïvePre-immunized Study Age (Yrs) > 65> 68>70 N=1094 % N=403 % N=417 % N=478 % N=1134 % N=1049 % N=463 % Cardiac Pulmonary Diabetes Renal Liver Asthma
10 Underlying Medical Conditions in PCV13 Recipients (at 1 st Dose) Underlying Medical Conditions in Prevnar13 Recipients at Initial Dose Evaluated by –Pneumococcal Vaccine Naïve and –Pre-immunized Status and by –Study
11 Safety Data Collection and Monitoring
12 Solicited Adverse Events Local and systemic reactions monitored daily for 14 days: –Electronic diary cards used to record information –Local events included Redness, swelling, pain, limitation of motion (LOM) –Systemic events included: Fever measured using oral digital thermometer daily (at bedtime and whenever fever suspected) Fatigue, headache, chills, rash, vomiting, decreased appetite, new generalized muscle pain, aggravated generalized muscle pain, new generalized joint pain and aggravated generalized joint pain –Data regarding medications to treat pain and fever collected in all studies, except study 004.
13 Analysis of Adverse Events (AEs) Solicited Local and Systemic AEs –Vaccine Naïve –Pre-immunized Unsolicited Adverse Events Deaths Discontinuations due to Adverse Event Serious Adverse Events (SAES)
14 Vaccine Naïve Subjects Studies 004 and 3010 Solicited Local Adverse Reactions Solicited Systemic Adverse Reactions
15 Local Reactogenicity Within 14 Days of PCV13 or 23vPS (Naïve) Local Reactions STUDY 004STUDY 3010 PCV13 23vPSPCV1323vPS yrs60-64 yrs N= % N= % N= % N= % N= % Redness Any Severe Swelling Any Severe Pain Any Severe Limitation of Motion Any Severe
16 Local Reactogenicity Within 14 Days of PCV13 or 23vPS (Naïve) Local Reactogenicity within 14 days of Vaccination in a Pneumococcal Vaccine Naïve Population (Study 004 and Study 3010) with –Prevnar13 or –PNEUMOVAX23
17 Systemic Reactogenicity Within 14 Days of PCV13 or 23vPS (Naïve) Systemic Reactions STUDY 004STUDY 3010 PCV13 23vPSPCV1323vPS yrs60-64 yrs N= % N= % N= % N= % N= % Any Fever (>38C) Fatigue Headache Chills Rash Vomiting Decreased Appetite New Myalgia Aggravated Myalgia New Joint Pain Aggravated Joint Pain Pain Meds N/A Fever Meds N/A
18 Systemic Reactogenicity Within 14 Days of PCV13 or 23vPS (Naïve) Systemic Reactogenicity within 14 days of Vaccination in a Pneumococcal Vaccine Naïve Population (Study 004 and Study 3010) with –Prevnar13 or –PNEUMOVAX23
19 Summary on Reactogenicity in Naïve Subjects Local Reactogenicity –Study 004 PCV 13 >23vPS for “any” redness/swelling/pain 23vPS >PCV13 for “severe” pain (8.6% > %) –Study 3010 PCV13 >23vPS for “any” pain (69.2 % vs 58.3%) Systemic Reactogenicity –Study 004 PCV13 vs 23vPS similar incidences of systemic reactions –Study vPS>PCV13 for decreased appetite, aggravated muscle pain, new joint pain, use of medication to treat fever
20 Pre-Immunized Subjects Studies 3000 and 3005 Solicited Local Reactions Solicited Systemic Reactions
21 Local Reactogenicity Within 14 days of PCV13 or 23vPS (Pre-Immunized) Local Reactions Study 3000 ( > 68 yrs. )Study 3005 ( > 70 yrs) > 1 dose 23vPS > 3 yrs prior1 dose 23vPS > 5 yrs prior PCV13 23vPS N= % N= % N= % Redness Any Severe Swelling Any Severe Pain Any Severe Limitation of Motion Any Severe
22 Local Reactogenicity Within 14 days of PCV13 or 23vPS (Pre-Immunized) Local Reactogenicity within 14 days of Vaccination in a Pre-Immunized Population (Prior receipt of PNEUMOVAX23) with –Prevnar13 or –PNEUMOVAX23
23 Systemic Reactogenicity Within 14 days of PCV13 or 23vPS (Pre-Immunized) Systemic Reactions Study 3000 ( > 68 yrs. ) > 1 dose 23vPS > 3 yrs prior Study 3005 ( > 70 yrs) 1 dose of 23vPS > 5 yrs prior PCV13 23vPS N= % N= % N= % Any Fever(>38C) >40C Fatigue Headache Chills Rash Vomiting Appetite Decreased New Myalgia Aggravated Myalgia New Joint Pain Aggravated Joint Pain Pain Meds Fever Meds
24 Systemic Reactogenicity Within 14 days of PCV13 or 23vPS (Pre-Immunized) Systemic Reactogenicity within 14 days of Vaccination in a Pre-Immunized Population (Prior receipt of PNEUMOVAX23) with Prevnar13 or PNEUMOVAX23
25 Summary of Reactogenicity: Pre-Immunized Subjects Local Reactogenicity –Study vPS > PCV13 for all local reactions Systemic Reactogenicity –Study vPS >PCV13 for fatigue, rash, new muscle pain (myalgia), aggravated muscle pain
26 Reactogenicity of Sequential Vaccine Administration (Studies 004 and 3010) Single dose 23vPS (naïve) compared to: –PCV13 /23vPS 1 year interval (study 3010) 3-4 year interval (extension study 004) –23vPS / 23vPS administered at 3-4 year interval (extension study 004)
27 Local Reactogenicity within 14 days Post Dose Local Reactions Yrs STUDY 004STUDY 3010 Year 0Year Year lYear 0 23vPS*PCV13 / 23vPS23vPS/ 23vPSPCV13 / 23vPS23vPS* N= % N=41-87 % N= % N= % N= % Redness Any Severe Swelling Any Severe Pain Any Severe Limitation of Motion Any Severe vPS* administered at Year 0 was years prior in Study 004 and was 1 year prior in Study 3010.
28 Local Reactogenicity within 14 days Post Dose Local Reactogenicity within 14 days of a Single Dose of PNEUMOVAX23 at Year 0 compared to a Subsequent Dose of PNEUMOVAX23 using a Dosing Interval of 1 Year and Years
29 Systemic Reactogenicity within 14 days Post Dose Systemic Reactions Age Yrs STUDY 004STUDY 3010 Year 0Year 3.5-4Year 1Year 0 23vPS*PCV13 / 23vPS23vPS/ 23vPSPCV13 / 23vPS23vPS* N= (%) N=43-68 (%) N= (%) N= (%) N= (%) Any Fever(>38C) Fatigue Headache Chills Rash Vomiting Decreased Appetite New Myalgia Aggravated Myalgia New Joint Pain Aggravated Joint Pain Pain MedsN/A Fever MedsN/A vPS* administered at Year 0 was years prior for Study 004 and was 1 year prior for Study 3010.
30 Systemic Reactogenicity within 14 days Post Dose Systemic Reactogenicity within 14 days of a Single Dose of PNEUMOVAX23 at Year 0 compared to a Subsequent Dose of PNEUMOVAX23 using a Dosing Interval of 1 Year and Years
31 Summary on Reactogenicity: Sequential Doses Solicited Local –Using a dosing interval of 3-4 yrs (extension study 004): 23vPS/23vPS is more reactogenic than PCV13/23vPS for redness, swelling and limitation of motion –Using a dosing interval of 1 year (study 3010): PCV13/23vPS is more reactogenic than 23vPS alone Solicited Systemic –Using a dosing interval of 3-4 yrs, 23vPS/23vPS is more reactogenic for rash when compared to 23vPS alone –Using a dosing interval of 1 yr, PCV13/23vPS is more reactogenic for rash and use of pain medications when compared to 23vPS alone
32 Reactogenicity of Concomitant Administration of PCV13 with Trivalent Influenza Vaccine (TIV) Studies 3001 and 3008 Solicited Adverse Reactions for PCV13 + TIV compared to PCV13: –Local –Systemic Reactogenicity of Concomitant Administration of PCV13 with Trivalent Influenza Vaccine (TIV) in a Pneumococcal Vaccine Naïve Population: Design for Studies 3001 and 3008 Study ArmsConcomitant Dose 1Dose 2 (1 month later) Group 1PCV13 + TIVPlacebo Group 2Placebo + TIVPCV13
33 Local Reactogenicity (PCV13+TIV vs PCV13) within 14 Days (Naïve) Study 3001 (age yrs)Study 3008 ( age > 65 yrs) Local Reactions PCV13 +TIV / Placebo Concomitant Dose 1 Placebo +TIV / PCV13 Dose 2 PCV13 +TIV/ Placebo Concomitant Dose 1 Placebo +TIV/ PCV13 Dose 2 N= % N= % N= % N= % Redness Any Severe Swelling Any Severe Pain Any Severe Limitation of Motion Any Severe
34 Local Reactogenicity (PCV13+TIV vs PCV13) within 14 Days (Naïve) Local Reactogenicity within 14 days of PCV13 Administered Concomitantly with TIV compared to PCV13 alone in a Pneumococcal Vaccine Naïve Population
35 Systemic Reactogenicity (PCV13 + TIV vs PCV13) within 14 Days (Naive) Systemic Reactions Study 3001 (Age yrs) Study 3008 (Age > 65 yrs) PCV13 +TIV /Placebo Concomitant Dose 1 Placebo +TIV /PCV13 Dose 2 PCV13 +TIV /Placebo Concomitant Dose 1 Placebo +TIV /PCV13 Dose 2 N = % N= % N= % N= % Any Fever(>38C) Fatigue Headache Chills Rash Vomiting Appetite Decreased New Myalgia Aggravated Myalgia New Joint Pain Aggravated Joint Pain Pain Meds N/A Fever Meds N/A
36 Systemic Reactogenicity (PCV13 + TIV vs PCV13) within 14 Days (Naive) Systemic Reactogenicity within 14 days of PCV13 Administered Concomitantly with TIV compared to PCV13 alone in a Pneumococcal Vaccine Naïve Population
37 Reactogenicity of Concomitant Administration of PCV13 with Trivalent Influenza Vaccine (TIV) Studies 3001 and 3008 (Naïve) Solicited Adverse Reactions for PCV13 + TIV compared to Placebo +TIV: –Local –Systemic Reactogenicity of Concomitant Administration of PCV13 with Trivalent Influenza Vaccine (TIV) in a Pneumococcal Vaccine Naïve Population: Design for Studies 3001 and 3008 Study ArmsConcomitant Dose 1Dose 2 (1 month later) Group 1PCV13 + TIVPlacebo Group 2Placebo + TIVPCV13
38 Local Reactogenicity (PCV13+TIV vs TIV+ Placebo) within 14 Days (Naïve) Local Reactions Study 3001 (Age yrs) Study 3008 (Age > 65 yrs) PCV13 +TIV / Placebo Concomitant Dose 1 Placebo +TIV / PCV13 Concomitant Dose 1 PCV13 +TIV /Placebo Concomitant Dose 1 Placebo +TIV / PCV13 Concomitant Dose 1 N= % N= % N= % N= % Redness Any Severe Swelling Any Severe Pain Any Severe Limitation of Motion Any Severe
39 Local Reactogenicity (PCV13+TIV vs TIV+ Placebo) within 14 Days (Naïve) Local Reactogenicity within 14 days of PCV13 Administered Concomitantly with TIV compared to PCV13 alone in a Pneumococcal Vaccine Naïve Population
40 Systemic Reactogenicity (PCV13 + TIV vs TIV+ Placebo) within 14 Days (Naive) Systemic Reactions Study 3001 (Age yrs) Study 3008 (Age > 65 yrs) PCV13 +TIV /Placebo Concomitant Dose 1 Placebo +TIV /PCV13 Concomitant Dose 1 PCV13 +TIV /Placebo Concomitant Dose 1 Placebo +TIV /PCV13 Concomitant Dose 1 N = % N= % N= % N= % Any Fever(>38C) Fatigue Headache Chills Rash Vomiting Appetite Decreased New Myalgia Aggravated Myalgia New Joint Pain Aggravated Joint Pain Pain Meds Fever Meds
41 Systemic Reactogenicity (PCV13 + TIV vs TIV+ Placebo) within 14 Days (Naive) Systemic Reatogenicity within 14 days of PCV13 administered concomitantly with TIV compared to TIV given with Placebo in a Pneumococcal Vaccine Naïve Population
42 Summary of Reactogenicity for Concomitant Administration of PCV13 +TIV compared to PCV13 and TIV+ Placebo: Studies 3001 and 3008 (Naïve) Solicited Local Reactogenicity –Study 3001 (age yrs) PCV13 (42%) > PCV13+TIV (35.6%) for “any” limitation of motion PCV13 +TIV > TIV for all local reactions Solicited Systemic Reactogenicity –Incidence of “any” fever (>38C) not increased with concomitant administration of PCV13+TIV compared to PCV13 or TIV + placebo in studies 3001 and –In study 3001 and 3008, when compared to PCV 13 or TIV+ placebo, PCV13+ TIV study arm had a higher incidence of these AEs: Fatigue Headache Chills Rash Decreased appetite New and aggravated muscle pain New joint pain Aggravated joint pain
43 Unsolicited Adverse Events within 1 Month Incidence across 6 studies for PCV13 was % Similar incidence in naïve and pre-immunized subjects Similar incidence for initial dose of PCV13 when compared to 23vPS in naïve and pre-immunized subjects: –Naïve subjects Study 004 (60-64 yrs) –PCV 13 (17.0%) vs 23vPS (16.7 %) Study 3010 (60-64 yrs) –PCV 13 (19.2%) vs 23vPS (20.7 %) –Pre-immunized subjects Study 3005 –PCV13 (14.9 % ) vs 23vPS (18.6%) Most frequent AEs reported for PCV13: –Infections and Infestations ( %) –Musculoskeletal ( %) –Gastrointestinal ( %) –General disorders and administration site conditions ( %)
44 Summary of 16 Deaths Across 6 Studies StudyVaccine AdministeredLast Dose Days Post-Dose Age at Death (Yrs) MedDRA Term 3008PCV13 +TIV / Placebo2372Cardiac Failure 3008Placebo +TIV / PCV Peritonitis 3001PCV13 +TIV / Placebo27155Hemoptysis vPS17285 Post-Procedure Pulmonary Embolus 3005PCV13 / PCV Atherosclerotic coronary artery disease 3005PCV Myocardial Infarction 3005PCV Cardiac Arrest vPS114175Cardiac Failure Congestive 3000PCV Metastatic Neoplasm 3000PCV Septic Shock 3000PCV Lung Neoplasm Malignant 3005PCV Colon Cancer 004PCV Hepatic neoplasm Malignant, Pancreatic carcinoma, Thrombosis vPS125677Acute Myocardial Infarction VPS126286Cardiac Arrest 3005PCV Atherosclerotic coronary artery disease
45 Summary of 16 Deaths Across 6 Studies Summay of 16 Deaths (Across 6 Studies) by: –Study –Vaccine Administered –Dose Number –Days Post-Dose –Age at Death –Cause of Death (MedDRA)
46 Deaths (Across 6 Studies) 16 subjects died: 2/16 deaths occurred within 30 days of vaccination –Cardiac Failure at 3 days after PCV13+TIV / Placebo –Peritonitis at 20 days after Placebo+TIV / PCV13 9/16 in study 3005 –Subjects ≥70 years of age 12/5667 (0.21%) received PCV13 or PCV13+TIV 4/1391 (0.29%) subjects received 23vPS
47 Summary of 16 Adverse Events leading to Discontinuation (6 Studies) StudyVaccine Administered Last Dose Days Post-Dose SeverityMedDRA Term 3001Placebo +TIV11ModerateFatigue and Headache 3005PCV13 / PCV1329SevereWorsening of COPD 3008PCC13 +TIV/ Placebo 210Life-threateningAngina pectoris, ECG ST segment elevation vPS123SevereProstate cancer vPS128SevereUnstable Angina vPS139Life-threateningMalignant Melanoma vPS1135ModerateHyperthyroidism, Mental Status Changes vPS1154SevereProstate cancer 3005PCV131174SevereMetastatic prostate cancer/bone vPS1235ModeratePolymyalgia 3005PCV131274Life-threateningCerebral Infarction vPS1284/297Severe / Moderate Atrial Flutter, Congestive Heart Failure / Pneumonia and Pericardial/pleural effusion status post drainage 00423vPS1290SevereLung cancer metastatic 3005PCV131323ModerateAbdominal Pain Upper 3005PCV131329ModerateBladder Neoplasm vPS1365SevereAdenocarcinoma
48 Summary of 16 Adverse Events leading to Discontinuation (6 Studies) Summary of 16 Adverse Events Leading to Discontinuation (Across 6 Studies) by: –Study –Vaccine Administered –Dose Number –Days Post-Dose –Severity and Cause (MedDRA)
49 Adverse Events leading to Discontinuation (Across 6 Studies) 16 subjects discontinued due to adverse events –7 of 16 subjects discontinued due to cancer 6 of 16 subjects received PCV13 9 of 16 subjects received 23vPS 1 of 16 subjects received TIV +placebo
50 Incidence of Serious Adverse Events after Initial Dose (6 Studies) Subjects with SAEsWithin 1 month n (%)Within 6 months n (%) Naïve Subjects: Study 004 Initial Dose PCV13 ( N= 417) (60-64 yrs)1 (0.2)12 (2.9) 23vPS (N= 414) 2 (0.5)10 (2.4) PCV13 (N= 403) (50-59yrs)2 (0.5)5 (1.2) Study 3010 (60-64 yrs) Initial Dose PCV13 (N= 478)2 (0.4)15 (3.1) 23vPS (N= 237)1 (0.4)6 (2.5) Study 3001 (50-59 yrs) PCV13+TIV / Placebo (N=551 / 538)4 (0.7) / 3 (0.6)18 (3.3) Placebo+TIV / PCV13 (N= 560 / 543)5 (0.9) / 6 (1.1)10 (1.8) Study 3008 (>65 yrs) PCV13+TIV / Placebo (N= 576) 4 (0.7) / 5 (0.9)No 6 month follow-up Placebo+TIV / PCV13 (N=575)0 (0) / 8 (1.4)No 6 month follow-up Pre-Immunized Subjects: Study 3000 ( > 68 yrs) PCV13 (N = 1049)10 (1.0)41 (3.9) Study 3005 ( >70 yrs) (Initial Dose) PCV13 (N= 463)3 (0.6)27 (5.8) 23vPS (N= 473)8 (1.7)26 (5.5)
51 Incidence of Serious Adverse Events after Initial Dose (6 Studies) Incidence of Serious Adverse Events after Initial Dose (Across 6 Studies) Within 1 Month and Within 6 Months by –Pneumococcal vaccine naïve status –Pre-immunized status –Study –Treatment arm
52 Serious Adverse Events (Initial Dose, 6 Studies) SAE range within 1 month of vaccination: –0.2% to 1.4% of PCV13 recipients –0.4% to 1.7% of 23vPS recipients. SAE range within 6 months of vaccination: –1.2% to 5.8% of PCV13 recipients –2.4% to 5.5% of 23vPS recipients Categories of SAE: –Age > 65 years Cardiac disorders, cerebrovascular events, neoplasms, respiratory disorders and injuries occurred more frequently than in younger subjects
53 Incidence of Serious Adverse Events after Subsequent Dose (3 Studies) Subjects with SAEsWithin 1 month n (%)Within 6 months n (%) Naïve Subjects: Study 004 Extension Study (Year 3-4) PCV13/ PCV13 (N =108) (60-64 yrs) 1(.01)*N/A PCV13/ 23vPS (N=108)1(.01)N/A 23vPS/ 23vPS (N=189) 0 (0)N/A PCV13 / PCV13 (N=214 ) (50-59yrs) 0 (0)N/A Study 3010 (Year 1) PCV13/ PCV13 (161) (60-64 yrs)0 (0)5 (3.1) PCV13/ 23vPS (266)2 (0.7)6 (2.2) 23vPS / PCV13 (223)1 (0.4)3 (1.3) Pre-Immunized Subjects: Study 3005 (Year 1) PCV13/ PCV13 (N= 391) (>70 yrs)4 (1.0)17 (4.3) 23vPS/ PCV13 (N= 404)7(1.7)21 (5.2) *Erythema multiforme at day 34.
54 Incidence of Serious Adverse Events after Subsequent Dose (3 Studies) Incidence of Serious Adverse Events after Subsequent Dose (Across 3 Studies: 004, 3010 and 3005) Within 1 Month and Within 6 Months by: Pneumococcal vaccine naïve status Pre-immunized status Study Vaccine schedule
55 Conclusions Regarding Safety In 6 clinical studies, which included vaccine naïve and adult subjects with prior receipt of PNEUMOVAX23, no imbalances in deaths or serious adverse events were detected in subjects who received Prevnar13 when compared to PNEUMOVAX23. No safety issues were identified for administration of Prevnar13, as a single dose, to vaccine naïve or pre-immunized adults aged > 50 years –the safety database is not large enough to detect rare events that could occur at a frequency lower than 0.1%. When Prevnar13 was concomitantly administered with TIV, systemic reactogenicity was increased in subjects aged yrs and subjects > 65 yrs when compared to administration of TIV or Prevnar13 alone. No data available for concomitant administration of Prevnar13 with adult vaccines other than TIV. No data available for use of Prevnar13 in immunocompromised adults. Safety data will be submitted from the randomized, placebo-controlled CAPITA trial of PCV13 for the prevention of vaccine type pneumococcal pneumonia conducted in 85,000 subjects aged > 65 years in the Netherlands. Safety data will include: –SAEs in the 28 days post-vaccination for subjects not in the immunogenicity cohort –SAEs for 6 months post-vaccination for the 2000 subjects in the immunogenicity cohort –Incidence rates of local, systemic and adverse events for all subjects in the immunogenicity cohort.