1. 1 13-valent pneumococcal conjugate vaccine (PCV13) – new ACIP recommendations 44 th National Immunization Conference April 21, 2010 Pekka Nuorti, MD, DSc National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention

2. Presentation outline Licensure of 13-valent pneumococcal conjugate vaccine (PCV13) Rates of invasive pneumococcal disease (IPD) and serotypes after PCV7 and before PCV13 Advisory Committee on Immunization Practices (ACIP) recommendations for use of PCV13 2

3. 3 13-valent pneumococcal conjugate vaccine (PCV13) Serotypes in PCV13 (Prevnar 13®) –PCV7 types: 4, 6B, 9V, 14, 18C, 19F, 23F –additional serotypes: 1, 3, 5, 6A, 7F, 19A Approved by FDA and recommended for use by ACIP on February 24, 2010 –Children 6 weeks through 5 years (71 months) of age Indications –Prevention of IPD caused by the 13 serotypes –Prevention of otitis media caused by PCV7 serotypes

4. 4 Overall incidence of IPD before and after PCV7, children <5 years, U.S.,1998 and 2007 CDC, Active Bacterial Core surveillance (ABCs). MMWR 2000;49 (RR-9); MMWR 2010;59 (No. 9):253-7

5. 5 Incidence of IPD before PCV13 by vaccine serotype group, children <5 years, U.S. 2007 Active Bacterial Core Surveillance (ABCs). MMWR 2010;59 (No. 9):253-7

6. 6 Proportion of IPD cases by vaccine serotype, children <5 years, U.S.,2007 PCV13 types: 64% Serotype Active Bacterial Core Surveillance (ABCs). MMWR 2010;59 (No. 9):253-7 42% 2%

7. 7 PCV13 – immunogenicity and safety Safety –13 clinical trials with >7400 infants and children –Common adverse reactions: injection site reactions, fever, decreased appetite, irritability, increased or decreased sleep –Safety profile comparable to PCV7 Immunogenicity –Randomized, U.S. multicenter study –PCV13 induced antibodies comparable to those shown to be protective against IPD in PCV7 Prevnar 13, Package Insert, February 2010

8. 8 ACIP recommendations for PCV13 PCV13 is recommended for –All children 2 through 59 months of age –Children 60 through 71 months who have underlying medical conditions that increase their risk of pneumococcal disease or complications MMWR 2010;59 (No.9):258-61

9. 9 Table 1

10. 10 Prevention of pneumococcal disease in children – recommendation overview 1.Routine recommendation Infants and children who have not previously received PCV7 or PCV13 2.Transition recommendation Children incompletely vaccinated with PCV7 or PCV13 3.Supplemental PCV13 dose recommendation Children completely vaccinated with PCV7 4.High risk children >6 years of age 5.PPSV23 after PCV13 Children >2 years with underlying medical conditions MMWR 2010;59 (No. 9):258-61

11. 11 1. No previous PCV7/PCV13 vaccination - routine recommendation

12. 12 Unvaccinated children <59 months –ACIP recommendation and immunization schedules for PCV13 are the same as for PCV7 1,2 –PCV13 replaces PCV7 for all doses Routine infant immunization –4-dose series at 2, 4, 6, and 12 to 15 months –fewer doses if series started at age >7 months 1) MMWR 2008;57: 343-4 2) MMWR 2000;49 (RR-9) Children who have not previously received PCV7 or PCV13

13. 13 Table 2 MMWR 2010;59 (No.9):258-61

14. 14 2. Incomplete PCV7/PCV13 vaccination - transition recommendation

15. 15 Table 3 Children previously vaccinated with PCV7 or PCV13 Children who have received 1 or more doses of PCV7 should complete their immunization series with PCV13

16. 16 Children >24 months who are incompletely vaccinated with PCV7 or PCV13* Healthy children 24 through 59 months with any incomplete PCV schedule (PCV7 or PCV13) –single dose of PCV13 Children 24 through 71 months with underlying medical conditions –any incomplete schedule of <3 doses of PCV (PCV7 or PCV13), 2 doses of PCV13 –if received 3 doses of PCV (PCV7 or PCV13), a single dose of PCV13 *Recommendations similar to PCV7; see MMWR 2008;57: 343-4.

17. 17 3. Complete PCV7 vaccination - supplemental PCV13 dose

18. 18 Supplemental PCV13 dose – ACIP considerations Local and systemic adverse reactions similar to 4 dose PCV13 series 1,2 Immune responses to 6 additional serotypes are comparable to 3-dose PCV13 infant series 1,2 Programmatic feasibility –implementation during first year after licensure –to be given at next medical visit – no active recall Cost-effective strategy 3 –In addition, potential for enhanced indirect effects 1) Prevnar 13 – package insert, February 2010 2) FDA Clinical Review, March 2010 3) Strutton D, Pfizer. ACIP June 2009; Messonnier M, CDC, ACIP Oct 2009

19. 19 Children with complete PCV7 vaccination A single supplemental dose of PCV13 is recommended for children who have received a complete, age-appropriate series of PCV7 –all children 14 through 59 months of age –children with an underlying medical condition through 71 months of age (including those who have already received a dose of PPSV23) Supplemental PCV13 dose should be given at the next medical visit and at least last 8 weeks after last PCV7 dose

20. 20 4. High risk children >6 years of age Studies among children >6 years with HIV or sickle cell disease underway to evaluate PCV13 safety and optimal number of doses A single dose of PCV13 may be administered to children 6 through 18 years of age who are at highest risk for IPD: –functional or anatomic asplenia, sickle cell disease –HIV-infection and other immunocompromising conditions –cochlear implant or CSF leaks MMWR 2010;59 (No. 9):258-61

21. 21 5. PPSV23 after PCV13 for children 2 through 18 years at increased risk for IPD In addition to PCV13, children with underlying medical conditions should receive PPSV23 at age >2 years Recommended doses of PCV13 should be completed before PPSV23 is given –Children who have previously received PPSV23 should also receive recommended PCV13 doses

22. Summary of key points PCV13 is recommended for all children <5 years of age and to children <6 years of age with underlying medical conditions Children who have received >1 dose of PCV7 should complete their immunization series with PCV13 Children who are completely vaccinated with PCV7 should receive a single dose of PCV13 22

23. Conclusions PCV13 succeeds PCV7 and provides broader protection against IPD for young children –includes serotype 19A, the most common cause of IPD among children Achieving and maintaining high PCV13 coverage can further reduce the burden of pneumococcal diseases in the U.S. 23

24. Additional information Licensure of a 13-valent pneumococcal conjugate vaccine (PCV13) and recommendations for use among children – Advisory Committee on Immunization Practices (ACIP), 2010 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5909a2.htm ACIP provisional recommendations for use of PCV13 http://www.cdc.gov/vaccines/recs/provisional/downloads/pcv13-mar-2010-508.pdf PCV13 Vaccine Information Statement (VIS) http://www.cdc.gov/vaccines/pubs/vis/default.htm Prevnar 13 Package Insert http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ ucm201667.htm Details of routine pneumococcal conjugate vaccine schedule http://www.cdc.gov/vaccines/recs/schedules/child-schedule.htm

25. BACK-UP SLIDES 25

26. 26

27. 27 ACIP Provisional Recommendations for use of PCV13. http://wwwhttp://www. cdc. gov/vaccines/recs/provisional

28. 28

29. PCV13 – dosing intervals Minimum age of administration: 6 weeks Minimum intervals: –4 weeks between doses 1 and 2 and doses 2 and 3 – 8 weeks between next-to-last and last doses 29

30. 30 Children with underlying medical conditions – ACIP considerations PCV13 is approved for use through 71 months of age Currently, no PCV13 safety or immunogenicity data available for children with chronic illness May have reduced antibody responses Likely remain at increased risk of IPD

31. 31 High risk children >6 years of age – ACIP considerations PCV7 licensed by FDA up to age 9 years Current ACIP and AAP/COID recommendations for PCV7 1,2 –Administering PCV7 to older children [>5 years] with high risk conditions is not contraindicated –Practitioners may consider administering PCV7 to HIV infected children aged 5-17 years on HAART who have not been previously immunized with PCV7 Studies of PCV13 among children >6 years with HIV infection and sickle cell disease underway to evaluate safety and optimal number of doses 1. MMWR 2000;49 (RR-9); ACIP, June 2008 2. AAP/COID Red Book, 28 th edition, 2009

32. 32 PPSV23 in high risk children who have received PCV13 - considerations Limited safety data for PPSV23 after PCV7 No safety or immunogenicity data available for PPSV23 given after (or before) PCV13 Clinical effectiveness unknown Opportunity to provide additional serotype coverage with PPSV23 may become limited –serotypes in PPSV23 but not in PCV13 caused 16 % of IPD cases in children 24 through 59 months with medical conditions 1 MMWR 2010;59(No. 9):253-7

33. 33 Proportion of IPD cases caused by serotypes in different vaccine formulations, children < 5 years, U.S. 2008 CDC, Active Bacterial Core surveillance, unpublished

34. 34 Proposed recommendation and schedule are the same as those currently recommended by ACIP for PPSV23 after PCV7

35. 35 Transition from PCV7 to PCV13 - ACIP considerations Comparable safety profile and immune responses A schedule of 3 PCV7 doses followed by 1 PCV13 dose vs. 4 PCV13 doses –may result in lower IgG antibody levels for 6 additional serotypes –functional OPA responses comparable after 4 th dose –clinical relevance not known 1 Program implementation and logistic considerations –interchangeability of vaccine doses 1.PCV13 – FDA clinical review, March 2010 http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ ucm201667.htm

36. 36 Antibody responses to 6 additional serotypes - 4 PCV13 doses vs. 3 PCV7 doses followed by 1 PCV13 dose - capsular polysaccharide IgG antibody GMCs (Wyeth Study 008)* µg/mL *Slide courtesy of Dr. P Paradiso, Pfizer

37. 37 Antibody responses to 6 additional serotypes - 4 PCV13 doses vs. 3 PCV7 doses followed by 1PCV13 dose - capsular polysaccharide IgG antibody: %>0.35 ug/ml (Wyeth Study 008) %>0.35 ug/ml *Slide courtesy of Dr. P Paradiso, Pfizer

38. 38 OPA GMT OPA antibody responses (GMTs) to 6 additional serotypes after 4 doses of PCV13 and 3 doses of PCV7 followed by 1 dose of PCV13* *In both groups, the proportion of subjects with OPA titers >1:8 was >97.8% Source: Paradiso P. ACIP meeting October 2009; Wyeth, Study 008 SEROTYPE

39. 39 Comparison of PCV13 Cost- effectiveness evaluations (1) “Public health and economic impact of PCV13” –Wyeth, June 2009 ACIP meeting Decision-analytic Markov model Routine PCV13 vs. PCV7 –cost-saving One-time supplemental PCV13 dose program –cost-saving if indirect effects accelerated by >6 mos –considered cost-effective also when indirect effects not included

40. 40 Comparison of PCV13 Cost- effectiveness evaluations (2) “Cost-effectiveness of PCV13 in infants and young children in the U.S.” –CDC, October 2009 ACIP meeting CEA, cohort model Routine PCV13 to replace PCV7 –likely cost-saving from societal perspective; >$129 million when productivity gains included Single supplemental PCV13 dose program –not cost-saving when indirect effects not considered –comparable in cost-effectiveness to other accepted interventions (approximately $16, 000 per QALY saved; range, $9,300 to $40,200) Messonnier M. 2010. ISPPD7, Tel Aviv, Israel

41. 41 Overall incidence of IPD by age group, children <18 years,U.S.1998-1999 and 2008 CDC, Active Bacterial Core surveillance, unpublished < 5 years: decrease from 99 to 21 per 100,000

42. 42 Proportion of IPD cases by vaccine serotype, children < 5 years, 2008 - PCV13 types: 61% - 19A, 7F, 3 account for 99% of PCV6 types CDC, Active Bacterial Core surveillance, unpublished Serotype, N=275

43. 43 Proportion of IPD cases caused by serotypes in different vaccine formulations, U.S. 2008 CDC, Active Bacterial Core surveillance, unpublished