1 Vaccines and Related Biological Products Advisory Committee Meeting November 18, 2009 Prevnar 13 Pneumococcal 13-valent Conjugate Vaccine [Diphtheria CRM 197 Protein] Applicant: Wyeth Pharmaceuticals Inc. Julienne Vaillancourt, R.Ph., M.P.H. Captain, US Public Health Service FDA/CBER

2 Names and Abbreviations  Prevnar 13  Pneumococcal 13-valent Conjugate Vaccine [Diphtheria CRM 197 Protein]  13-valent pneumococcal conjugate vaccine  13vPnC  PCV13

3 Prevnar 13  Each 0.5 mL dose contains:  2.2 µg of saccharide from each of pneumococcal serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, and 23F  4.4 µg of saccharide from pneumococcal serotype 6B  32 µg of CRM 197 carrier protein  mg Aluminum as AlPO 4 adjuvant  0.02% polysorbate 80  5mM succinate buffer  Single-dose, pre-filled syringe  Intramuscular administration  4 dose series at 2, 4, 6, and months of age.  Store at 2 to 8°C / 36 to 46°F (refrigerate – do not freeze)

4 Proposed Indication For the prevention of invasive disease and otitis media caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F in infants and toddlers.

5 BLA Regulatory Context  Infant clinical development program  Immunogenicity-based  Considered:  Advice from March 7, 2001, VRBPAC Meeting  WHO recommendations for development of new pneumococcal conjugate vaccines  Granted Fast Track  Priority Review

6 Prevnar 13 Agenda 11/18/2009 AM 8:10Introduction and Questions for Committee  Julienne Vaillancourt, R.Ph., M.P.H., FDA 8:20Epidemiology of IPD in the US  Matthew Moore, M.D., M.P.H, CDC 9:05Sponsor Presentation - Wyeth Pharmaceuticals Inc.  Emilio A. Emini, Ph.D.  William C. Gruber, M.D.  Daniel A. Scott, M.D. 10:35Break 10:50FDA Presentations: Primary Immunogenicity Endpoints - Lucia Lee, M.D. Safety and Effectiveness of 13vPnC - Tina Khoie, M.D., M.P.H. Pharmacovigilance/Vaccine Effectiveness - Robert Wise, M.D., M.P.H.

7 Prevnar 13 Agenda 11/18/2009 PM 12:20Lunch 1:20Open Public Hearing 1:50FDA Presentation of Questions - Tina Khoie, M.D., M.P.H., FDA 1:55Committee Discussion and Recommendations

8 Questions for the Committee

9 1.Are the available data adequate to support the effectiveness of Prevnar 13, when administered to infants and toddlers at 2, 4, 6, and months of age, for the prevention of invasive pneumococcal disease caused by serotypes in the vaccine?

10 Questions for the Committee 2.Are the available data adequate to support the safety of Prevnar 13 when administered to infants and toddlers at 2, 4, 6, and months of age?

11 Questions for the Committee 3.Please comment on the proposed phase 4 observational safety study.

12 Questions for the Committee 4.Please discuss whether the available data support the effectiveness of Prevnar 13 for the prevention of otitis media.

13 Questions for the Committee 5.Please comment on the proposed postmarketing IPD effectiveness studies.