Indication for Otitis Media FDA Vaccine and Related Biologicals Advisory Committee Meeting May 21, 2002 Pneumococcal 7-Valent Conjugate Vaccine (Diphtheria CRM 197 Protein) Prevnar ® Wyeth Vaccines

Introduction of Otitis Media George Siber, M.D.C.M. Sr. VP and Chief Scientific Officer, Wyeth Vaccines Efficacy of Prevnar ® Against Otitis Media in Finland Terhi Kilpi, M.D., Ph.D. Senior Researcher and Head of Dept. of Vaccines National Public Health Institute, Helsinki OM Efficacy from Northern California Kaiser Permanente Steve Black, M.D. Co-Director, Vaccine Center, NCKP Conclusions George Siber, M.D.C.M. Schedule of Presentations

Background of Otitis Media Disease and Studies to Support the Indication  Clinical Manifestations of Pneumococcal Disease  Otitis Media Epidemiology  Otitis Media Indication  Overview of Prevnar OM trials

Pneumo 45% N. Mening Hi Strep B Meningitis (1-23 mos) Pneumo 40% NTHi Other Morax. Otitis Media & Sinusitis Pneumo 97% N. Mening Bacteremia/Sepsis Pneumo 63% Other Pneumonia Contributions of Streptococcus pneumoniae to Major Bacterial Infections of U.S. Children

Otitis media Pneumonia Bacteremia Meningitis Estimated number of cases per year 5 million 71,000 17,000 1,400 Streptococcus pneumoniae: Pathogen With Significant Disease Burden in Children < 5

Background of Otitis Media Disease and Studies to Support the Indication  Clinical Manifestations of Pneumococcal Disease  Otitis Media Epidemiology  Otitis Media Indication  Overview of Prevnar OM trials

Incidence of Otitis Media by Age and Sex Among 18,942 Children in Control Group Incidence of Otitis Media by Age and Sex Among 18,942 Children in Control Group Source: NCKP Prevnar Efficacy Trial

Physician Visits for Otitis Media Regardless of Etiology Visits (000s) Age (Years) Source: Scott-Levin Physician Drug & Diagnosis Audit Jan-Dec ,711 4,451 2,708 2,125 1,873 1,452 1,

1. MMWR. 2000;49(RR-9): Hall MJ, Lawrence L. Adv Data Vital Health Stat. 1998;300: Gates GA. Otolaryngol Head Neck Surg. 1996;114:  Most common cause of sick child visits  Leading reason for prescribing antibiotics during childhood 1  Use of antibiotics for treatment contributes to increase in antimicrobial resistance 1  Tympanostomy tube insertion is the most common pediatric surgical procedure requiring general anesthesia 2  Estimated annual costs (direct plus indirect) exceed $5 billion in children < 5 years of age 3 Impact of Otitis Media

Penicillin Resistant Pneumococci - US “Almost all the resistant strains are serogroups 6,14,19,23 and 9” Infectious Dis Child, Feb ‘96 E. Shapiro, MD Yale University E. Shapiro, MD Yale University

Wald et al Pediatr Infect Dis J : % 85.4% Cross-reactive Serotypes Vaccine Serotypes Non-vaccine Serogroups Cumulative Percentage % of all pneumo AOM caused by each serotype Serotypes causing Acute Otitis Media in U.S. Children ( ) (4 children’s hospitals; n=564) Serotypes causing Acute Otitis Media in U.S. Children ( ) (4 children’s hospitals; n=564) Inpatient and Outpatient Cases Ages: 16 days – 13.8 years. (mean age 26.6 mos.)

Background of Otitis Media Disease and Studies to Support the Indication  Clinical Manifestations of Pneumococcal Disease  Otitis Media Epidemiology  Otitis Media Indication  Overview of Prevnar OM trials

 “...active immunization of infants and toddlers against invasive disease and otitis media caused by S. pneumoniae due to capsular serotypes included in the vaccine” Proposed Otitis Media Indication

Rationale for Otitis Media Indication  Supported by two randomized controlled trials showing statistically significant decreases in OM outcomes  Prevnar immunization has an important medical effect on otitis media disease and its consequences  Addition to label ensures accurate communication of information to physicians and parents

Background of Otitis Media Disease and Studies to Support the Indication  Clinical Manifestations of Pneumococcal Disease  Otitis Media Epidemiology  Otitis Media Indication  Overview of Prevnar OM trials

 FinOM Efficacy - Juhani Eskola, MD and Terhi Kilpi, MD  FinOM Follow-up - Terhi Kilpi, MD  NCKP Efficacy - Steven Black, MD and Henry Shinefield, MD Prevnar ® OM Trials Prevnar ® OM Trials

2 Black S, Shinefield H et al. Pediatr Infect Dis J. 2000;19: Eskola J et al. N Engl J Med. 2001; 344: Prevnar ® Efficacy Trials for Otitis Media (OM) FinOM Trial 1  Finnish infants  2, 4, 6, 12–15 mo  N = 1,662  Myringotomy, cultures performed NCKP Trial 2  US infants  2, 4, 6, 12–15 mo  N = 37,868  Automated database searched for OM visits

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