selected clinical data presentations

Transcription

1 selected clinical data presentations PREVNAR 13 is a registered trademark of Wyeth LLC. Manufactured by Wyeth Pharmaceuticals Inc. Marketed by Pfizer Inc. PSA Pfizer Inc. All rights reserved. June 2013

2 introduction On behalf of Pfizer Vaccines, we are pleased to provide you with selected clinical data presentations from the phase 3 clinical study program for nar 13 (Pneumococcal 13-valent Conjugate Vaccine [Diphtheria CRM 197 Protein]). As part of the licensure for the adult indication for nar 13, 6 clinical trials were conducted that included over 6000 subjects. These clinical trials evaluated the safety, tolerability, and immunogenicity of nar 13 in adults over 50 who had either never received the pneumococcal polysaccharide vaccine (PPSV) in the past, or who had been immunized with PPSV more than 5 years earlier. In addition, 2 studies evaluated the safety, tolerability, and immunogenicity of concomitant administration of trivalent inactivated influenza vaccine (TIV) and nar 13. This resource includes those posters and data presentations from the clinical program that have been presented as of February 2012, and are supportive of the current FDA-approved Prescribing Information. Select information has been removed from the data presentation slides for consistency with the Prescribing Information. Also, this resource does not include data generated from the clinical program that have not yet been published. We hope you find this resource useful as you gather data to inform your formulary decisions. For questions related to the clinical program, please contact your local Pfizer sales representative or Pfizer Medical Information at Indications nar 13 is a vaccine indicated for active immunization for the prevention of disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F In adults 50 years and older for pneumococcal pneumonia and invasive disease. Indication is based on immune responses In children 6 weeks through 17 years for invasive disease caused by the 13 serotypes, and for children 6 weeks through 5 years of age for otitis media caused by 7 of the 13 serotypes only (4, 6B, 9V, 14, 18C, 19F, and 23F) Limitations of Use and Effectiveness nar 13 will only help protect against S pneumoniae serotypes in the vaccine Effectiveness when administered <5 years after pneumococcal polysaccharide vaccine is not known Important Safety Information Severe allergic reaction (eg, anaphylaxis) to any component of nar 13 or any diphtheria toxoid containing vaccine is a contraindication Immunocompromised individuals or individuals with impaired immune responsiveness due to the use of immunosuppressive therapy may have reduced antibody response

3 Important Safety Information (cont d) In adults, antibody responses to nar 13 were diminished when given with inactivated Influenza Virus Vaccine In adults, the commonly reported solicited adverse reactions were pain, redness, and swelling at the injection site, limitation of arm movement, fatigue, headache, muscle or joint pain, decreased appetite, chills, or rash Apnea following intramuscular vaccination has been observed in some infants born prematurely. Vaccination of premature infants should be based on the infant s medical status, and the potential benefits and risks In infants and toddlers, the most commonly reported serious adverse events were bronchiolitis (0.9%), gastroenteritis (0.9%), and pneumonia (0.9%) In children 6 weeks through 17 years, the most commonly reported solicited adverse reactions were injection site tenderness, redness, or swelling, irritability, decreased appetite, decreased or increased sleep, and fever. Most commonly reported side effects in children 5 years through 17 years also included hives CONCOMITANT ADMINISTRATION WITH TRIVALENT INFLUENZA VACCINE In adults, nar 13 was administered concomitantly with TIV for the 2007/2008 influenza season. In clinical trials it was shown that antibody responses to nar 13, when administered concomitantly with TIV, were diminished when compared to nar 13 administered alone. There are no data on the concomitant administration of nar 13 with diphtheria toxoid containing vaccines and other vaccines licensed for use in adults 50 years of age and older. In the 2 studies of concomitant administration of nar 13 with TIV in adults years of age and in adults 65 years of age and older who were PPSV-unvaccinated, the frequencies of local reactions were similar whether nar 13 was administered alone or with TIV, with the exception of mild redness at the injection site. Frequencies of local reactions within 14 days postvaccination in adults aged 50 through 59 years and in adults aged 65 years were similar after nar 13 was administered with TIV compared to nar 13 administered alone, with the exception of mild redness at the injection site, which was increased when nar 13 was administered concomitantly with TIV. An increase in some solicited systemic reactions within 14 days postvaccination was noted when nar 13 was administered concomitantly with TIV compared with TIV given alone (headache, chills, rash, decreased appetite, muscle and joint pain) or with nar 13 given alone (fatigue, headache, chills, decreased appetite, and joint pain).

4 table of contents nar 13, Adult Indication, Data Presentations at Scientific Meetings Title Population Meeting Poster: Safety and Immunogenicity of 13-valent Pneumococcal Conjugate Vaccine Given Concomitantly with Trivalent Inactivated Influenza Vaccine in Healthy Adults Presentation: 13-Valent Pneumococcal Conjugate Vaccine Given Concomitantly With Trivalent Inactivated Influenza Vaccine in Healthy Adults: A Randomized, Double-Blind, Phase 3 Clinical Trial Presentation: Immunogenicity and Safety of a 13-valent Pneumococcal Conjugate Vaccine in Pneumococcal Vaccine Naïve Adults 50 Through 64 Years of Age Presentation: Immunogenicity and Safety of a 13-valent Pneumococcal Conjugate Vaccine in Adults 70 Years of Age and Older iously Vaccinated with 23-valent Pneumococcal Polysaccharide Vaccine Adults 65+ Adults years Adults years Adults 70+ American Geriatrics Society, 2009 Infectious Diseases Society of America, 2009 European Congress of Clinical Microbiology and Infectious Diseases, 2011 European Congress of Clinical Microbiology and Infectious Diseases, 2011

5 Safety and Immunogenicity of 13-valent Pneumococcal Conjugate Vaccine Given Concomitantly with Trivalent Inactivated Influenza Vaccine in Healthy Adults TF Schwarz, 1 J Flamaing, 2 HC Rumke, 3 J Penzes, 4 C Juergens, 5 A Wenz, 5 D Jayawardene, 6 PC Giardina, 7 WC Gruber, 7 B Schmoele-Thoma 5 1 Stiftung Juliusspital Wuerzburg, Germany; 2 Dept of Geriatric Medicine, Univ Hospital Leuven, Belgium; 3 Vaxinostics, Rotterdam, The Netherlands; 4 Konszenzus Plusz Kft, Csongrád, Hungary; 5 Wyeth Research, Muenster, Germany; 6 Wyeth Research, Collegeville, PA, USA; 7 Wyeth Vaccines Research, Pearl River, NY, USA The research reported on this poster was supported by Wyeth Vaccines Research, Collegeville, PA. The investigators retained full independence in the conduct of this research /D34 ABSTRACT METHODS RESULTS BACkGROUND: Safety, tolerability and immunogenicity of 13-valent pneumococcal conjugate vaccine (PCV13) given with (+) trivalent inactivated influenza vaccine (TIV) in adults naive to 23-valent pneumococcal polysaccharide vaccine were evaluated. This study provides data on the compatibility of the vaccines before start of a large-scale Netherlands-based 2008 efficacy study against community-acquired pneumonia, in which half of the patients may be given PCV13 and TIV concomitantly. METHODS: Subjects aged 65 (N=1160) were randomly assigned (1:1 ratio) to receive at 0 and 1 month PCV13+TIV followed by placebo or TIV+placebo followed by PCV13. Immune responses to TIV (A/H1N1, A/H3N2, B antigens) and PCV13 (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) were determined before and 1 month after vaccination. Local reactions and systemic events were assessed. RESULTS: The percentage of evaluable subjects (PCV13+TIV n=549; TIV+placebo n=547) with a 4-fold increase in TIV antibody titer after PCV13+TIV compared to TIV+placebo was A/H1N1 80.3% vs 78.6%, A/H3N2 58.0% vs 62.6%, B 52.2% vs 54.0%. Noninferiority was met for all except A/H3N2, with lower limit of CI = -10.4%, slightly below the predefined lower limit of -10%. The percentage of subjects with HAI titers 40 was 94.0%, 96.5%, 81.9% for A/ H1N1, A/H3N2 and B after PCV13+TIV. PCV13 IgG geometric mean concentrations (GMCs) 1 month after PCV13+TIV were 1.08 to µg/ml, and 1 month after PCV13 alone were 1.15 to µg/ml; noninferiority (GMC ratio > 0.5 [2-fold criterion]) was met for all serotypes except 19F, with lower bound of CI=0.49. For PCV13+TIV compared to (1) TIV+placebo, (2) PCV13 alone, any local reactions were mainly mild: 46.9% vs (1)15.9%, (2) 46.6%; systemic events were more frequent after PCV13+TIV: 60.2% vs (1) 50.7%, (2) 48.6%. CONCLUSIONS: PCV13+TIV has an acceptable safety and immunogenicity profile compared to TIV or PCV13 given alone. BACkGROUND AND OBJECTIVES Although 23-valent pneumococcal polysaccharide vaccine (PPV) covers invasive disease due to Streptococcus pneumoniae in older adults, it is associated with poorly defined efficacy against pneumococcal pneumonia, lack of priming, and a decline of antibodies over 5 years at different rates for the 23 serotypes. 1 7-valent (4, 6B, 9V, 14, 18C, 19F, and 23F) and 9-valent (1, 5, 4, 6B, 9V, 14, 18C, 19F, and 23F) CRM197 conjugate pneumococcal vaccines have demonstrated efficacy against invasive pneumococcal disease and pneumonia in infants and children. 2-6 A 13-valent (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) pneumococcal conjugate vaccine (PCV13) has been shown to be safe and immunogenic in children <2 years of age. 7 Study objectives were to investigate whether concomitant administration of PCV13 and trivalent inactivated influenza vaccine (TIV) is safe and whether immune responses are non-inferior to those of TIV and PCV13 given alone. Design, Subjects, and Treatment Subjects were generally healthy adults 65 years of age who were naive to PPV. Figure 1. Study Schedule After After 0 Months 1 month 2 months Dose 1 Dose 2 Group 1 = Blood PCV13 Blood Placebo Blood draw + TIV draw draw PCV13+TIV/Placebo n = 580 Randomization (1:1) N = 1160 Blood Placebo Blood PCV13 Blood Group 2 = draw + TIV draw draw Placebo+TIV/PCV13 n = 580 Immunogenicity Assessments Immune response to TIV antigens A/H1, A/H3 and B as measured by standard hemagglutination inhibition assays (HAI) Immune response to pneumococcal antigens as measured by ELISA (serotype-specific immunoglobulin G [IgG] concentrations) Safety Assessments Local reactions and systemic events collected within 14 days after each vaccination using an electronic diary Adverse events reported throughout the study Statistical Analysis This study was designed to investigate: Noninferiority of immune responses induced by TIV when administered concomitantly with PCV13 compared to TIV alone, 1 month after vaccination with TIV For TIV antigens, seroconversion was a 4-fold increase in HAI titers from pre-vaccination to 1 month post vaccination. Noninferiority was declared if the lower limit of the 2-sided 95% CI (based on Chan and Zhang procedure 8 ) for the difference in percentage of responders between the 2 groups was > -10%. Noninferiority of immune responses to the PCV13 serotypes induced by PCV13 when administered concomitantly with TIV compared to PCV13 alone in a subset of 605 subjects For the 13 pneumococcal serotypes, IgG geometric mean concentrations (GMCs) for each serotype were compared between groups. Noninferiority was declared if the lower limit of the 2-sided 95% CI for the GMC ratio was >0.5 1 month after receipt of PCV13. Safety and tolerability of PCV13+TIV compared to PCV13 and to TIV given alone In addition, the 3 criteria for efficacy in subjects aged > 60 years taken from the Note for Guidance on Harmonization of Requirements for Influenza Vaccines by the European Medicines Agency 9 (EMEA) for the annual release of inactivated influenza vaccine were assessed for TIV. Percentage of subjects with seroconversions or significant increase in antihemagglutinin antibody titer >30% Geometric mean fold rise (GMFR) >2.0 More than 60% of subjects achieving an HAI titer 40 Subjects 1160 subjects were randomized to Group 1 or Group 2. The evaluable immunogenicity population included randomized subjects who met all inclusion criteria, had at least 1 valid and determinate assay result for the proposed analysis, and had no major protocol violations (n=1096, Group 1=549, Group 2=547). The safety population included all randomized subjects who received at least 1 dose of study vaccine (n=1151; Group 1=576; Group 2=575). Demographic characteristics of subjects in the safety population were similar to those of the evaluable immunogenicity population. The distribution of demographic characteristics was similar between groups (Table 1). Table 1. Demographic Characteristics, Evaluable Immunogenicity Population Sex, n (%) Vaccine Group (As Randomized) PCV13+TIV/Placebo, n=549 Placebo+TIV/PCV13, n=547 Female 276 (50.3) 274 (50.1) Male 273 (49.7) 273 (49.9) White 543 (98.9) 543 (99.3) Asian 3 (0.5) 2 (0.4) Race, n (%) Other 2 ( 0.4) 1 (0.2) Black or African 1 ( 0.2) 1 (0.2) American Age at vaccination, years 72.0 ± 5.5 ( 65-93) 72.0 ± 5.4 (65-93) mean ±SD (range) Immune Response Response to TIV The percentage of subjects achieving a 4-fold increase in HAI titers was similar in the 2 treatment groups; the noninferiority criterion for PCV13 + TIV relative to TIV alone was met for A/H1N1 and B. For A/H3N2, the difference in percentage of responders was slightly less than the predefined margin of -10%, with a lower limit of the 95% CI of (Table 2). The GMFR of TIV + PCV13 was similar to the GMFR after TIV alone (Table 3). All criteria proposed in the Note of guidance for annual release of inactivated TIV were exceeded for all 3 influenza antigens after PCV13 + TIV. The percentage of responders for A/H1N1, A/H3N2, and B all exceeded the required 30% (Table 2). GMFR exceeded the required 2.0 (Table 3). Percentage of subjects achieving HAI titers 40 for A/H1N1, A/H3N2, and B after PCV13+TIV exceeded the required 60% (Table 4). Response to PCV13 The noninferiority criterion for pneumococcal IgG GMC ratios > 0.5 (2-fold criterion) was met 1 month after receipt of PCV13+TIV versus 1 month after receipt of PCV13 for all serotypes except 19F, for which the lower limit of the 95% CI was 0.49, just below the predetermined lower limit of 95% CI>0.5 (Table 5). The noninferiority criterion for GMC ratios >0.5 (2-fold criterion) was met for all serotypes 1 month after dose 2, ie, 2 months after PCV13 +TIV compared to 1 month after PCV13 (Table 6). Table 5: Comparison of Pneumococcal IgG Geometric Mean Table 6: Comparison of Pneumococcal IgG Geometric Mean Table 2. Percentage of Subjects With a 4-Fold Increase in Titer for Concomitant Concentrations 1 Month After PCV13+TIV and 1 Month Concentrations 2 Months After PCV13+TIV and 1 Month Vaccine Antigens after Dose 1 Evaluable Immunogenicity Population After PCV13 Evaluable Immunogenicity Population After PCV13 Evaluable Immunogenicity Population Vaccine Group (as Randomized) Vaccine Group (As Randomized) Vaccine Group (As Randomized) Concomitant PCV13+TIV/Placebo Placebo+TIV/PCV13 PCV13+TIV/Placebo Placebo+TIV/PCV13 Vaccine Comparison PCV13+TIV/Placebo Placebo+TIV/PCV13 Vaccine Comparison Vaccine N n % (95% CI) N n % (95% CI) Difference (95% CI) Serotype n GMC n GMC Ratio (95% CI) Serotype n GMC n GMC Ratio (95% CI) TIV: HAIs ( 0.60, 1.04) ( 0.56, 0.97) A/H1N ( 76.7, 83.5) ( 74.9, 81.9) 1.7 ( -3.1, 6.5) ( 0.78, 1.13) ( 0.78, 1.13) A/H3N ( 53.7, 62.2) ( 58.4, 66.6) -4.6 (-10.4, 1.3) ( 0.51, 0.87) ( 0.51, 0.88) B ( 47.9, 56.4) ( 49.7, 58.3) -1.8 ( -7.8, 4.1) ( 0.55, 0.86) ( 0.60, 0.93) PCV13=13-valent pneumococcal conjugate vaccine; TIV= Trivalent inactivated influenza vaccine; N = Number of subjects with 6A ( 0.61, 0.94) 6A ( 0.67, 1.05) valid and determinate assay results at the given visit; n=number of subjects with a 4-fold increase in titer 6B ( 0.75, 1.25) 6B ( 0.66, 1.09) 7F ( 0.67, 1.07) 7F ( 0.69, 1.11) 9V ( 0.63, 1.02) 9V ( 0.65, 1.03) Table 3. Standard Hemagglutination Inhibition Assay Geometric Mean Titers ( 0.53, 0.97) ( 0.56, 1.01) Before and After Dose 1 and Geometric Mean Fold Rise after Dose 1 18C ( 0.64, 1.01) 18C ( 0.61, 0.96) Evaluable Immunogenicity Population 19A ( 0.56, 0.87) 19A ( 0.52, 0.82) Sampling Time 19F ( 0.49, 0.85) 19F ( 0.52, 0.88) Postdose 1/ TIV: Randomized Predose 1 Postdose 1 Predose 1 23F ( 0.71, 1.27) 23F ( 0.68, 1.20) PCV13=13-valent pneumococcal conjugate vaccine; TIV= Trivalent inactivated influenza PCV13=13-valent pneumococcal conjugate vaccine; TIV= Trivalent inactivated influenza HAIs Vaccine Sequence n GMT (95% CI) n GMT (95% CI) n GMFR (95% CI) vaccine; n = Number of subjects with valid and determinate assay results at the given visit; vaccine; n = Number of subjects with valid and determinate assay results at the given visit; PCV13+TIV/Placebo (19.9, 23.6) (176.6, 216.4) (8.1, 10.1) GMC=Geometric mean concentration GMC=Geometric mean concentration A/H1N1 Placebo+TIV/13vPnC (20.5, 24.6) (173.4, 212.5) (7.7, 9.5) PCV13+TIV/Placebo (55.8, 70.9) (293.5, 365.2) (4.6, 5.9) Figure 2. Percentage of Subjects with Local Reactions A/H3N2 Placebo+TIV/13vPnC (57.5, 74.1) (370.5, 460.8) (5.5, 7.2) at the PCV13 Injection Site Within 14 days After Vaccination CONCLUSIONS PCV13+TIV/Placebo (20.4, 24.3) (81.6, 100.2) (3.7, 4.5) B 50 PCV13+TIV Placebo+TIV/13vPnC (20.6, 24.6) (79.8, 98.1) (3.6, 4.3) PCV13 Immune responses to TIV given concomitantly 40 PCV13=13-valent pneumococcal conjugate vaccine; TIV= Trivalent inactivated influenza vaccine; n = Number of subjects with with PCV13 are comparable to immune responses valid and determinate assay results at the given visit; GMT=Geometric mean titer; GMFR=Geometric mean fold rise 30 after TIV administered alone. 20 Immune responses to PCV13 given concomitantly Table 4: Percentage of Subjects Achieving HAI Titer with TIV as measured by IgG GMCs are After Dose 1 Evaluable Immunogenicity Population uniformly less than immune responses after 0 Vaccine Group (as Randomized) Any Redness Swelling Pain Arm movement PCV13 administered alone; however, these Concomitant limitation PCV13+TIV/Placebo Placebo+TIV/PCV13 lower responses meet statistical criteria for Vaccine PCV13=13-valent pneumococcal conjugate vaccine N n % (95% CI) N n % (95% CI) TIV= Trivalent inactivated influenza vaccine noninferiority and are unlikely to be clinically TIV: HAIs significant. A/H1N (91.6, 95.8) (91.8, 96.0) Figure 3. Percentage of Subjects with Systemic Reactions Local reactions at the PCV13 site were comparable A/H3N (94.6, 97.9) (95.7, 98.6) Within 14 Days after Dosing* and systemic events were more common after B (78.5, 85.1) (77.8, 84.5) concomitant administration of PCV13 and TIV than PCV13=13-valent pneumococcal conjugate vaccine; TIV= Trivalent inactivated influenza vaccine; N = Number of subjects Joint pain worse after single administration. Fever rates were low with valid and determinate assay results at the given visit; n=number of subjects with an antibody concentration that meets criterion HAI titer 40 New joint pain and comparable in all groups. Muscle pain worse Overall, the study demonstrated an acceptable New muscle pain Decreased appetite safety and immunogenicity profile for the Safety Vomiting concomitant administration of PCV13 and TIV. Rash Local reactogenicity at the injection site was similar for PCV13 +TIV relative to Chills PCV13 alone (46.9% vs 46.6%) (Figure 2). Severe redness occurred in 0.7% and Headache 1.0%; severe swelling, 0.2% and 0.0%; severe pain, 1.4% and 2.6%, and severe Fatigue REFERENCES limitation of arm movement in 1.9% and 1.4% of patients, PCV13 +TIV and PCV13 Fever 40 PCV13 1. Dear K, Holden J, Andrews R, Tatham D. Vaccines for preventing pneumococcal infection in adults. Cochrane alone, respectively. Fever 39 to 40 Placebo+TIV Database Syst Rev. 2003;(4):CD Fever 38.5 to <39 PCV13+TIV 2. Klugman KP, Madhi SA, Huebner RE, et al. A trial of a 9-valent pneumococcal conjugate vaccine in children Systemic events were more frequent after PCV13 + TIV than TIV alone with and those without HIV infection. N Engl J Med. 2003;349: Fever 38 to < Cutts FT, Zaman SM, Enwere G, et al. Efficacy of nine-valent pneumococcal conjugate vaccine against (60.2% vs 50.7%) and than PCV13 alone (60.2% vs 48.6%) (Figure 3). pneumonia and invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled Any trial. Lancet. 2005;365: Grijalva CG, Nuorti JP, Arbogast PG, Martin SW, Edwards KM, Griffin MR. Decline in pneumonia admissions Overall, the rate of fever was low and similar after PCV13+TIV relative to TIV after routine childhood immunisation with pneumococcal conjugate vaccine in the USA: a time-series % Subjects analysis. Lancet. 2007; 369: alone and PCV13 alone. 5 Grijalva CG, Griffin MR. Population-based impact of routine infant immunization with pneumococcal conjugate PCV13=13-valent pneumococcal conjugate vaccine; TIV= Trivalent inactivated influenza vaccine vaccine in the USA. Expert Rev Vaccines. 2008;7: Serious adverse events occurred in <1% of patients in either group after *Dose 1 for PCV13 + TIV and Placebo +TIV; Dose 2 for PCV13 6. Black S, Shinefield H, Fireman B, et al. Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Pediatr Infect Dis J. 2000;19: % CIs indicate between-group difference, PCV13+TIV vs PCV13 PCV13+TIV or either vaccine alone, and were primarily cardiac in nature; 7. Bryant K, Block SL, Scott D. Safety and immunogenicity of a 13-valent pneumococcal conjugate vaccine. 95% CIs indicate between-group difference, PCV13+TIV vs Placebo +TIV Presented at : 25th Annual Meeting of the European Society for Paediatric Infectious Diseases, May 2-4, 2007, Porto, Portugal. none was considered to be related to vaccine. 8. Chan ISF, Zhang Z. Test based exact confidence intervals for the difference of two binomial proportions. Biometrics. 1999;55: Note for Guidance on Harmonization of Requirements for Influenza Vaccines. EMEA 12 March, CPMP/ BWP/214/96. % Subjects Presented at the American Geriatrics Society Annual Scientific Meeting, April 29th-May 1st, 2009, Chicago, IL

6 13 Valent Pneumococcal Conjugate Vaccine Given Concomitantly With Trivalent Inactivated Influenza Vaccine in Healthy Adults: A Randomized, Double Blind, Phase 3 Clinical Trial RW Frenck Jr, 1 A Gurtman, 2 J Rubino, 3 W Smith, 4 M van Cleeff, 5 D Jayawardene, 6 PC Giardina, 2 D Giorgio, 2 EA Emini, 2 WC Gruber, 2 B Schmöle Thoma 7 1 Cincinnati Children s Hospital Medical Center, Cincinnati, OH, USA; 2 Pfizer Inc, Pearl River, NY, USA; 3 Raleigh Medical Group, Raleigh, NC, USA; 4 University of Tennessee Medical Center, Knoxville, TN, USA; 5 Cary Medical Research, Cary, NC, USA; 6 Pfizer Inc, Collegeville, PA, USA; 7 Pfizer Inc, Münster, Germany Presented at the 47th Annual Meeting of the Infectious Diseases Society of America (IDSA) on October,

7 Influenza Major public health concern in elderly Annual influenza vaccination recommended for adults >50 years of age Coadministration of influenza vaccine and pneumococcal vaccine is an attractive option Presented at the 47th Annual Meeting of the Infectious Diseases Society of America (IDSA) on October,

8 Coprimary Objectives Immune responses to trivalent inactivated influenza vaccine (TIV) administered concomitantly with PCV13 are noninferior to TIV alone Measured by hemagglutination inhibition (HAI) assay for all 3 vaccine strains 1 month after TIV Non inferiority was met for each virus strain if the lower limit of the 95%CI for the difference in proportions of responders was > 10% Immune responses to PCV13 administered concomitantly with TIV are noninferior to PCV13 administered 1 month after TIV Measured by serotype specific immunoglobulin G (IgG) concentrations Non inferiority was met for each of the 13 serotypes if the lower limit of the 95%CI for the GMC ratio >0.5 (2 fold criterion) Presented at the 47th Annual Meeting of the Infectious Diseases Society of America (IDSA) on October,

9 Key Study Criteria Inclusion criteria Healthy adults aged 50 to 59 years No previous vaccination against pneumococcus Exclusion criteria Td or Tdap 6 months before to 1 month after vaccination Documented pneumococcal infection in previous 5 years Selected severe chronic conditions, immune disorders, or allergy/previous reaction to chicken or egg proteins Td=tetanus diphtheria; Tdap=tetanus diphtheria with acellular pertussis. Presented at the 47th Annual Meeting of the Infectious Diseases Society of America (IDSA) on October,

10 Vaccines PCV13 Serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F 2.2 µg of each saccharide, except for 6B (4.4 µg) Polysaccharides conjugated to CRM 197 TIV (2007/2008 season) A/Solomon Islands/3/2006 [H1N1] A/Wisconsin/67/2005 [H3N2] B/Malaysia/2506/2004 Presented at the 47th Annual Meeting of the Infectious Diseases Society of America (IDSA) on October,

11 Study Design Double blind, randomized, multicenter Presented at the 47th Annual Meeting of the Infectious Diseases Society of America (IDSA) on October,

12 Demographic Characteristics: Evaluable Immunogenicity Population PCV13 +TIV/Placebo (n=531) Placebo +TIV/PCV13 (n=532) Sex, n Female/Male 310/ /226 Race, n (%) White 487 (91.7) 488 (91.7) Age at Vaccination (y) Mean (SD) 54.6 (2.8) 54.6 (2.9) Presented at the 47th Annual Meeting of the Infectious Diseases Society of America (IDSA) on October,

13 Percentage of Subjects Achieving 4 fold Increase in Titer for Flu Antigens 1 month after TIV TIV: HAI PCV13 + TIV /Placebo % (95% CI) Placebo + TIV /PCV13 % (95% CI) Difference % (95% CI) A/H1N (80.6, 87.0) 81.2 (77.6, 84.4) 2.8 (-1.8, 7.4) A/H3N (67.1, 75.0) 69.5 (65.4, 73.4) 1.6 (-3.9, 7.2) B 60.6 (56.3, 64.8) 60.3 (56.0, 64.5) 0.3 (-5.6, 6.2) Presented at the 47th Annual Meeting of the Infectious Diseases Society of America (IDSA) on October,

14 Standard HAI Geometric Mean Titer (GMT) and Geometric Mean Fold Rise (GMFR) 1 month after TIV TIV: HAI A/H1N1 A/H3N2 B Randomized Vaccine Sequence PCV13 + TIV /Placebo Placebo +TIV /PCV13 PCV13 + TIV /Placebo Placebo + TIV /PCV13 PCV13 + TIV /Placebo Placebo + TIV /PCV13 Predose 1 GMT (95% CI) (23.29, 29.08) (21.86, 27.19) (37.86, 49.83) (43.08, 56.75) (12.89, 15.19) (13.60, 16.23) Postdose 1 GMT (95% CI) (300.60, ) (298.31, ) (399.84, ) (427.43, ) (60.70, 75.51) (69.99, 86.56) GMFR (95% CI) (11.28, 14.41) (11.93, 15.42) (8.87, 11.74) 9.66 (8.37, 11.16) 4.84 (4.35, 5.37) 5.24 (4.70, 5.85) Presented at the 47th Annual Meeting of the Infectious Diseases Society of America (IDSA) on October,

15 Serotype Pneumococcal IgG Geometric Mean Concentrations (GMC) PCV13 + TIV /Placebo GMC (µg/ml) Placebo + TIV/ PCV13 GMC (µg/ml) B V C F F Ratio (95% CI) 0.69 (0.55, 0.87) 0.75 (0.60, 0.93) 0.71 (0.59, 0.86) 0.77 (0.60, 0.98) 0.72 (0.58, 0.88) 0.86 (0.67, 1.10) 0.84 (0.66, 1.08) Presented at the 47th Annual Meeting of the Infectious Diseases Society of America (IDSA) on October,

16 Pneumococcal IgG GMCs PCV13 + TIV /Placebo Placebo + TIV/ PCV13 Serotype GMC (µg/ml) GMC (µg/ml) Ratio (95% CI) (0.58, 0.95) (0.66, 0.93) 0.84 (0.67, 1.05) 6A (0.70, 1.06) 7F (0.63, 0.95) 19A (0.74, 1.08) Presented at the 47th Annual Meeting of the Infectious Diseases Society of America (IDSA) on October,

17 Safety Local Reactions Systemic Adverse Events Presented at the 47th Annual Meeting of the Infectious Diseases Society of America (IDSA) on October,

18 1 TOC Presentation Immunogenicity and Safety of a 13-valent Pneumococcal Conjugate Vaccine in Pneumococcal Vaccine Naïve Adults 50 Through 64 Years of Age L. Jackson 1, A. Gurtman 2, M. van Cleeff 3, K. U. Jansen 2, D. Jayawardene 4, C. Devlin 2, D. Scott 2, E. Emini 4, W. Gruber 2, B. Schmoele-Thoma 5 1 Group Health Research Institute, Seattle, WA, USA; 2 Pfizer Inc, Pearl River, NY, USA; 3 Cary Medical Research, Cary, NC, USA; 4 Pfizer Inc, Collegeville, PA, USA; 5 Pfizer Inc, Berlin, Germany Presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Diseases on May 9, 2011

19 Incidence of Invasive Pneumococcal Disease (IPD) and Community-Acquired Pneumonia (CAP), United States 2 IPD < CAP < J.C. Nelson et al. Vaccine, 26 (2008) Presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Diseases on May 9, 2011

20 3 TOC Study Design Healthy adults years of age with no history of pneumococcal vaccination Adults y PCV13 N=370 PPSV23 N=370 Opsonophagocytic antibody titers at baseline and 1 month after vaccination. On a subset at 1 year. Adults y PCV13 N=370 Presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Diseases on May 9, 2011

21 Noninferiority PCV13 : PPSV23 in Subjects Years of Age 4 Healthy adults years of age with no history of pneumococcal vaccination Adults y Adults y PCV13 N=418 PPSV23 N=417 PCV13 Noninferiority of immune response to PCV13 vs PPSV23 to the common serotypes Superiority of 6A serotype immune response to PCV13 vs PPSV23 N=406 Presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Diseases on May 9, 2011

22 OPA GMT Ratios - Dose 1 PCV13 : PPSV23 in Subjects Years of Age (146:104) Noninferiority criteria: 95% LCI > (93:85) 1.6 (2062:1295) Noninferiority criteria met for all 12 common serotypes (2593:213) 1.2 (199:162) 6A Superiority criteria: 95% LCI > 1.0 Superior response for 8 of 12 serotypes in common Superior response (95% LCI >2) for serotype 6A (not in PPSV23) 14 19F 18C 19A 6B 7F 9V 2.5 (1984:788) 2.8 (1120:405) 2.9 (1164:407) 0.9 (612:692) 1.9 (1726:925) 1.9 (682:352) 1.0 (517:539) 23F 5.2 (375:72) Presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Diseases on May 9, 2011

23 Noninferiority PCV13 : PCV13 6 Healthy adults years of age with no history of pneumococcal vaccination Adults y Adults y PCV13 N=418 PPSV23 N=417 PCV13 Noninferiority of immune response to PCV13 in year old group compared with the year old group N=406 Presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Diseases on May 9, 2011

24 OPA GMT Ratios to PCV13 - Dose 1 Subjects Years of Age vs Subjects Years of Age (200:146) Noninferiority criteria met for all serotypes Response to 9 of 13 serotypes significantly greater for yo vs yo F 6B 6A 1.0 (91:93) 1.4 (2833:2062) 1.4 (269:199) 1.7 (4328:2593) 1.6 (3212:1984) 1.4 (1520:1120) 9V 1.5 (1726:1164) (957:612) 18C 1.1 (1939:1726) 19A 1.4 (956:682) 19F 23F 1.2 (599:517) 1.3 (494:375) Presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Diseases on May 9, 2011

25 8 TOC Safety Presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Diseases on May 9, 2011

26 Subjects Reporting Local Reactions: Swelling and Redness 9 Percentage of Subjects yo PCV yo PCV yo PPSV23 Swelling Percentage of Subjects yo PCV yo PCV yo PPSV23 Redness Any Mild Mod Sev 0 Any Mild Mod Sev Absent: no or minimal redness or swelling: 0 to <2.5 cm Mild: 2.5 to 5.0 cm Moderate: 5.1 to 10.0 cm Severe: >10.0 cm Presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Diseases on May 9, 2011

27 Subjects Reporting Local Reactions: Pain yo PCV yo PCV yo PPSV23 * Mild: awareness of sign or symptom, but easily tolerated Percentage of Subjects Moderate: discomfort enough to cause interference with usual activity Severe: incapacitating, with inability to do usual activity 10 ** 0 Any Mild Mod Sev *Significantly higher for PCV13 vs PPSV23; **Significantly higher for PPSV23 vs PCV13 (only apply to yo group) Presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Diseases on May 9, 2011

28 Subjects Reporting Local Reactions: Limitation of Arm Movement yo PCV yo PCV yo PPSV23 Absent: no limitation of arm movement Percentage of Subjects Mild: some limitation of arm movement Moderate: unable to move arm above head, but able to move arm above shoulder Severe: unable to move arm above shoulder 10 0 Any Mild Mod Sev Presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Diseases on May 9, 2011

29 Naive subjects yo reporting systemic events: PCV13 vs PPSV23 Systemic Event PCV13 (%) PPSV2 3 (%) Difference (95 % CI) P- value 12 Any fever ( 38 C) (-0.6,7.1) 0.1 Mild fever ( 38 C but 38.5 C) (-0.6,7.1) 0.1 Moderate fever ( 38.5 C but 39 C) (-1.6,3.2) 0.52 Severe fever ( 39 C but 40 C) (-2.1, 2.2) >.99 Potentially life threatening ( 40 C) (-2.1, 2.2) >.99 Fatigue (-6.5,9.8) 0.72 Headache (-9.1,8.3) 0.93 Chills (-9.0,7.8) 0.92 Rash (-3.7,10.7) 0.34 Vomiting (-6.2,3.1) 0.55 Decreased appetite (-8.5,7.6) 0.94 New generalized muscle pain (-10.2,7.0) 0.71 Aggravated muscle pain (-13.8,4.2) 0.3 New generalized joint pain (-14.4,2.9) 0.19 Aggravated joint pain (-4.7,11.8) 0.42 Presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Diseases on May 9, 2011

30 Naive Subjects yo Reporting Systemic Events: PCV13 vs PPSV yo yo Systemic Event % PCV13 % PCV13 % PPSV23 p-value* Fever Any ( 38 C) Mild ( 38 C but <38.5 C) Moderate ( 38.5 C but <39 C) Severe ( 39 C but 40 C) >0.99 Potentially life threatening (>40 C) Fatigue Headache Chills Rash Vomiting Decreased appetite New generalized muscle pain Aggravated generalized muscle pain New generalized joint pain Aggravated generalized joint pain Any systemic event * p-value refers only to the difference in the group yr; PCV13 vs PPSV23 Presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Diseases on May 9, 2011

31 Unsolicited Adverse Events, Serious AEs, and Deaths 14 Incidence of AEs and SAEs reported was low and similar between the 3 groups Reported SAEs: None considered related to study vaccine by the investigator y old: PCV13 group: 12 subjects (2.9%) PPSV23 group: 10 subjects (2.4%) y old: PCV13 group: 5 subjects (1.2%) One death: y old: PCV13 recipient (0.2%) Due to pancreatic and liver cancer Considered not related to the study vaccine Presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Diseases on May 9, 2011

32 15 TOC Conclusions PCV13 induces responses in naïve year olds that are: Noninferior to PPSV23 for all serotypes Statistically significantly greater for 8 of 12 common serotypes and Superior for serotype 6A The response to PCV13 is generally higher in years of age group compared to years of age group (9 of the PCV13 serotypes) PCV13 has an acceptable safety and reactogenicity profile in subjects years of age Presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Diseases on May 9, 2011

33 1 TOC Presentation Immunogenicity and Safety of a 13-valent Pneumococcal Conjugate Vaccine in Adults 70 Years of Age and Older iously Vaccinated With 23-valent Pneumococcal Polysaccharide Vaccine L Jackson 1, A Gurtman 2, K Rice 3, K Pauksens 4, RN Greenberg 5, T Jones 2, D Jayawardene 6, J Love 7, DA Scott 2, EA Emini 6, WC Gruber 2, B Schmoele-Thoma 8 1 Group Health Research Institute, Seattle, WA, USA; 2 Pfizer Inc, Pearl River, NY, USA; 3 VA Medical Center, Minneapolis, MN, USA; 4 Infektionskliniken, Uppsala University Hospital, Sweden; 5 Chandler Medical Center, Lexington, KY, USA; 6 Pfizer Inc, Collegeville, PA, USA; 7 Blair & Company, LLC, Greenwich, CT, USA; 8 Pfizer Inc, Berlin, Germany Presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Diseases on May 9, 2011

34 2 TOC Study Design Enrollment 1 Year Adults 70+ years of age who received PPSV23 5 yrs prior to enrollment PCV13 N=462 PPSV23 PCV13 PCV13 N=462 Opsonophagocytic antibody titers prior to and at 1 month after each vaccination. Presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Diseases on May 9, 2011

35 Noninferiority PCV13 vs PPSV23 3 Enrollment 1 Year Adults 70+ years of age who received PPSV23 5 yrs prior to enrollment PCV13 N=464 PPSV23 PCV13 PCV13 N=474 Presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Diseases on May 9, 2011

36 OPA GMT Ratios PCV13 vs PPSV23 4 Noninferiority criteria: 95% LCI >0.5 Noninferiority criteria met for all serotypes (81:55) 1.1 (55:49) 2.7 (545:203) Superiority criteria: 95% LCI > (72:36) Superior response for 10 of 12 serotypes Superior response (95% LCI >2) for serotype 6A (not in PPSV23) 7F 9V 6B 9.6 (903:94) 6A * 3.0 (1261:417) 1.5 (245:160) 2.0 (181:90) (280:285) 18C 1.9 (907:481) 19A 1.8 (354:200) 19F 1.6 (333:214) 23F 3.7 (158:43) Presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Diseases on May 9, For specific GMT ratios and values, click on a serotype. *Serotype 6A is not contained in PPSV23. GMT=geometric mean titer; OPA=opsonophagocytic assay.

37 5 TOC OPA GMTs to PCV13 and PPSV23 by age group PCV PCV PCV PPSV PPSV PPSV GMT A 6B 7F 9V 14 18C 19A 19F 23F Presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Diseases on May 9, 2011

38 OPA GMT Ratios PCV13 : PPSV23 by Age Group years years 80 years A 5 5 * 6A * 6A * 7F 6B 7F 6B 7F 6B 9V 9V 9V C 18C 18C 19A 19A 19A 19F 19F 19F 23F 23F 23F Serotype 6A is not contained in PPSV23. All figures show the ratio of PCV13:PPSV23. Presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Diseases on May 9, 2011 *

39 Noninferiority PCV13 / PCV13 vs PCV13 7 Enrollment 1 Year Adults 70+ years of age who received PPSV23 5 yrs prior to enrollment PCV13 N=464 PPSV23 PCV13 PCV13 N=474 Presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Diseases on May 9, 2011

40 Subjects Reporting Local Reactions to PCV13 and PPSV23 Given at Enrollment Redness and Swelling 8 Redness Swelling Percentage of Subjects PCV13 PPSV23 PCV13 PPSV * 30 * * 20 * * * 10 * 0 Any Mild Mod Sev Any Mild Mod Sev Percentage of Subjects Absent: no or minimal redness or swelling: 0 to <2.5 cm Mild: 2.5 to 5.0 cm Moderate: 5.1 to 10.0 cm Severe: >10.0 cm *Significantly higher for PPSV23 vs PCV13 Presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Diseases on May 9, 2011

41 Subjects Reporting Local Reactions to PCV13 and PPSV23 Given at Enrollment - Pain PCV13 PPSV23 Percentage of Subjects * Mild: awareness of sign or symptom, but easily tolerated Moderate: discomfort enough to cause interference with usual activity Severe: incapacitating, with inability to do usual activity 10 0 Any Mild Mod Sev *Significantly higher for PPSV23 vs PCV13 Presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Diseases on May 9, 2011

42 Subjects Reporting Local Reactions to PCV13 and PPSV23 Given at Enrollment Limitation of Arm Movement 10 PCV PPSV23 Percentage of Subjects * * Absent: no limitation of arm movement Mild: some limitation of arm movement Moderate: unable to move arm above head, but able to move arm above shoulder Severe: unable to move arm above shoulder 10 0 * * Any Mild Mod Sev *Significantly higher for PPSV23 vs PCV13 Presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Diseases on May 9, 2011

43 11 TOC Systemic events: PCV13 vs PPSV23 at enrollment Event Fever PCV13 % PPSV23 % Difference (95% CI) P-value Any ( 38 C) (-3.8, 0.9) 0.25 Mild ( 38 C but <38.5 C) (-3.4, 1.2) 0.53 Moderate ( 38.5 C but <39 C) (-1.2, 1.3) >.999 Severe ( 39 C but 40 C) (-1.8, 0.9) 0.51 Potentially life threatening (>40 C) (-1.2, 1.3) >.999 Fatigue (-16.4, -2.2) 0.01 Headache (-8.9, 4.3) 0.51 Chills (-8.1, 1.3) 0.16 Rash (-14.3, -4.0) <.001 Vomiting (-1.9, 2.7) 0.81 Decreased appetite (-6.1, 3.9) 0.69 New generalized muscle pain (-15.2, -0.6) 0.03 Aggravated generalized muscle pain (-13.6, -0.3) 0.04 New generalized joint pain (-7.7, 3.1) 0.41 Aggravated generalized joint pain (-10.3, 0.6) 0.08 Use of medication to treat pain (-11.2, 1.9) 0.17 Use of medication to treat fever (-6.8, 0.2) 0.06 Presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Diseases on May 9, 2011

44 Unsolicited Adverse Events, Serious AEs, and Deaths 12 Incidence of AEs after initial vaccination PCV13 group 14.9% PPSV23 group 18.6% Similar incidence of AEs after vaccination 2 SAEs ranging between 0.6% (PCV13 vax1) and 1.7% (PPSV23/PCV13 vax2) 1 case of idiopathic thrombocytopenic purpura in PPSV23/PCV13 group considered related by the investigator. Reported 6 month post vaccination 2. 9 deaths (5 in PCV13 group, 4 in PPSV23 group) None vaccine related Presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Diseases on May 9, 2011

45 Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM 197 Protein) only For Intramuscular Injection Only PAA HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use PREVNAR 13 safely and effectively. See full prescribing information for PREVNAR 13. PREVNAR 13 (Pneumococcal 13-valent Conjugate Vaccine [Diphtheria CRM 197 Protein]) Suspension for intramuscular injection Initial US Approval: 2010 RECENT MAJOR CHANGES Indications and Usage, Children 6 Years Through 17 Years of Age (1.2) 12/2012 Dosage and Administration, Vaccination Schedule for Children 6 Years Through 17 Years of Age (2.6) 12/2012 INDICATIONS AND USAGE In children 6 weeks through 5 years of age (prior to the 6th birthday), nar 13 is indicated for: active immunization for the prevention of invasive disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F. (1.1) active immunization for the prevention of otitis media caused by S. pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. No otitis media efficacy data are available for serotypes 1, 3, 5, 6A, 7F, and 19A. (1.1) In children 6 years through 17 years of age (prior to the 18 th birthday), nar 13 is indicated for: active immunization for the prevention of invasive disease caused by S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (1.2) In adults 50 years of age and older, nar 13 is indicated for: active immunization for the prevention of pneumonia and invasive disease caused by S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F. This indication is based on immune responses elicited by nar 13. There have been no controlled trials in adults demonstrating a decrease in pneumococcal pneumonia or invasive disease after vaccination with nar 13. (1.3) Limitations of nar 13 Use and Effectiveness nar 13 does not protect against disease caused by S. pneumoniae serotypes that are not in the vaccine. (1.4) The effectiveness of nar 13 administered less than 5 years after 23 valent pneumococcal polysaccharide vaccine is not known. (1.4) DOSAGE AND ADMINISTRATION Children 6 weeks through 5 years: The four-dose immunization series consists of a 0.5 ml intramuscular injection administered at 2, 4, 6, and months of age. (2.3) Children 6 through 17 years of age: a single dose. (2.6) Adults 50 years and older: a single dose. (2.7) FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS AND USAGE 1.1 Children 6 Weeks Through 5 Years of Age 1.2 Children 6 Years Through 17 Years of Age 1.3 Adults 50 Years of Age and Older 1.4 Limitations of nar 13 Use and Effectiveness 2 DOSAGE AND ADMINISTRATION 2.1 Preparation for Administration 2.2 Administration Information 2.3 Vaccination Schedule for Infants and Toddlers 2.4 Vaccination Schedule for Unvaccinated Children 7 Months Through 5 years of Age 2.5 Vaccination Schedule for Children iously Vaccinated With nar (Pneumococcal 7-valent Conjugate Vaccine [Diphtheria CRM 197 Protein]) 2.6 Vaccination Schedule for Children 6 Years Through 17 Years of Age 2.7 Vaccination Schedule for Adults 50 Years of Age and Older 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 5 WARNINGS AND PRECAUTIONS 5.1 Management of Allergic Reactions 5.2 Altered Immunocompetence 5.3 Apnea in Premature Infants 6 ADVERSE REACTIONS 6.1 Clinical Trials Experience With nar 13 in Children 6 weeks Through 17 years of Age 6.2 Clinical Trials Experience With nar 13 in Adults 50 Years of Age 6.3 Clinical Trials Experience With nar in Infants and Toddlers 6.4 Post-marketing Experience With nar 13 in Infants and Toddlers 6.5 Post-marketing Experience With nar in Infants and Toddlers FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE 1.1 Children 6 Weeks Through 5 Years of Age In children 6 weeks through 5 years of age (prior to the 6 th birthday), nar 13 is indicated for: active immunization for the prevention of invasive disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F. active immunization for the prevention of otitis media caused by S. pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. No otitis media efficacy data are available for serotypes 1, 3, 5, 6A, 7F, and 19A. 1.2 Children 6 Years Through 17 Years of Age In children 6 years through 17 years of age (prior to the 18 th birthday), nar 13 is indicated for: active immunization for the prevention of invasive disease caused by S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F. 1.3 Adults 50 Years of Age and Older In adults 50 years of age and older, nar 13 is indicated for: active immunization for the prevention of pneumonia and invasive disease caused by S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F. This indication is based on immune responses elicited by nar 13. There have been no controlled trials in adults demonstrating a decrease in invasive pneumococcal disease or pneumococcal pneumonia after vaccination with nar Limitations of nar 13 Use and Effectiveness nar 13 does not protect against disease caused by S. pneumoniae serotypes that are not in the vaccine. The effectiveness of nar 13 administered less than 5 years after Pneumovax 23 (23 valent pneumococcal vaccine polyvalent, PPSV23) is not known [see Clinical Studies 14.3]. DOSAGE FORMS AND STRENGTHS 0.5 ml suspension for intramuscular injection, supplied in a single-dose prefilled syringe. (3) CONTRAINDICATIONS Severe allergic reaction (e.g., anaphylaxis) to any component of nar 13 or any diphtheria toxoid-containing vaccine. (4) WARNINGS AND PRECAUTIONS Apnea following intramuscular vaccination has been observed in some infants born prematurely. Decisions about when to administer an intramuscular vaccine, including nar 13, to infants born prematurely should be based on consideration of the individual infant s medical status, and the potential benefits and possible risks of vaccination. (5.3) ADVERSE REACTIONS In infants and toddlers vaccinated at 2, 4, 6, and months of age in US clinical trials, the most commonly reported solicited adverse reactions were irritability (>70%), injection site tenderness (>50%), decreased appetite (>40%), decreased sleep (>40%), increased sleep (>40%), fever (>20%), injection site redness (>20%), and injection site swelling (>20%). (6.1) In adults aged 50 years and older the commonly reported solicited adverse reactions were pain at the injection site (>50%), fatigue (>30%), headache (>20%), muscle pain (>20%), joint pain (>10%), decreased appetite (>10%), injection site redness (>10%), injection site swelling (>10%), limitation of arm movement (>10%), chills (>5%) or rash (>5%). (6.2) To report SUSPECTED ADVERSE REACTIONS, contact Wyeth Pharmaceuticals Inc. at or VAERS at or DRUG INTERACTIONS In adults, antibody responses to nar 13 were diminished when given with inactivated Influenza Virus Vaccine. (14.3) USE IN SPECIFIC POPULATIONS Pregnancy: Safety and effectiveness of nar 13 in pregnant women have not been established. (8.1) Pediatric Use: Safety and effectiveness of nar 13 in children below the age of 6 weeks have not been established. (8.4) Geriatric Use: Antibody responses to nar 13 were lower in persons >65 years of age compared to antibody responses in persons 50 through 59 years of age. (8.5) See 17 for PATIENT COUNSELING INFORMATION Revised: 01/ DRUG INTERACTIONS 7.1 Concomitant Immunizations 7.2 Immunosuppressive Therapies 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 8.3 Nursing Mothers 8.4 Pediatric Use 8.5 Geriatric Use 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 14 CLINICAL STUDIES 14.1 nar Efficacy Data 14.2 nar 13 Clinical Trials in Children 6 Weeks Through 17 Years of Age 14.3 nar 13 Immunogenicity Clinical Trials in Adults 14.4 Concomitant Vaccine Administration 16 HOW SUPPLIED/STORAGE AND HANDLING 17 PATIENT COUNSELING INFORMATION 17.1 Potential Benefits and Risks 17.2 Adverse Reactions * Sections or subsections omitted from the full prescribing information are not listed 2 DOSAGE AND ADMINISTRATION 2.1 Preparation for Administration Since this product is a suspension containing an adjuvant, shake vigorously immediately prior to use to obtain a homogenous, white suspension in the vaccine container. Do not use the vaccine, if it cannot be resuspended. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration [see Description (11)]. This product should not be used if particulate matter or discoloration is found. Do not mix nar 13 with other vaccines/products in the same syringe. 2.2 Administration Information For intramuscular injection only. Do not inject intravenously, intradermally, or subcutaneously. Each 0.5 ml dose is to be injected intramuscularly using a sterile needle attached to the supplied prefilled syringe. The preferred sites for injection are the anterolateral aspect of the thigh in infants and the deltoid muscle of the upper arm in toddlers, children and adults. The vaccine should not be injected in the gluteal area or areas where there may be a major nerve trunk and/or blood vessel. 2.3 Vaccination Schedule for Infants and Toddlers nar 13 is to be administered as a four-dose series at 2, 4, 6, and months of age. Table 1: Vaccination Schedule for Infants and Toddlers Dose Dose 1 a,b Dose 2 b Dose 3 b Dose 4 c Age at Dose 2 months 4 months 6 months months a Dose 1 may be given as early as 6 weeks of age. b The recommended dosing interval is 4 to 8 weeks. c The fourth dose should be administered at approximately months of age, and at least 2 months after the third dose.