Pneumococcal Vaccines Update 2011 Prepared for the COI meeting 24 th Dec 2011

1. Pneumococcal Vaccines Update 2011Prepared for the COI meeting 24th Dec 2011 Dr Suhas V. Prabhu

2. Burden of disease - recent updates based on review of literature (national & global); • Brief report of any cost-effective analysis published in last 6-12 months; • Clinical trials: ongoing/planned/completed; • New recommendations from other agencies; • Contentious issues, if any.

3. Burden of Disease –Pneumonet Data* • 2 year prospective study • Based in 3 Bengaluru hospitals • Study of IPD (culture of S. pneumoniae from a normally sterile site) and pneumonia as defined clinically and on X-ray • Interim data for 1 year • Poster at ESPID- June 2011 Incidence of IPD in children < 2 years is 15.91(pn) + 6.82(pyomen) + 5.55(bact) = 28.28/1,00,000 population * Study Funded by Wyeth, a division of Pfizer Inc.

4. Burden of Disease –Pneumonet Data These are total pneumonia cases. Incidence of Pneumococcal pneumonia has to be by extrapolation on possible fraction of S. pneumonae as a cause of pneumonia in this age groups

5. Burden of disease - recent updates based on review of literature (national & global); • Brief report of any cost-effective analysis published in last 6-12 months; • Clinical trials: ongoing/planned/completed; • New recommendations from other agencies; • Contentious issues, if any.

6. Cost Effectiveness data -Issues • Cost effectiveness will depend on whether restricted to “serious diseases” only (IPD) or others like AOM • Assumed incidence rates for AOM varied highly in different studies from 20,952 to 118,000 per 1,00,000 children aged 0 – 10 years • PCV7 efficacy rates for AOM in 2 early studies were only 6-8% • Other studies had rates varying from 12% to 57% depending on vaccine used and whether direct effects alone or additionally herd immunity effects were included Boonacker CV et.al. Pharmacoeconomics 2011 Mar 29(3):199-211 doi: 102165/11584930-000000000-00000

7. Cost-effectiveness data – Singapore* • PCV-13 prevented 834 cases and 7 deaths due to IPD in the vaccinated population, and 952 cases and 191 deaths in the unvaccinated population (herd effect) over the 5-year time horizon. • Including herd effects, the cost-effectiveness ratio for PCV-13 was USD $37,644 per QALY. Without herd effect, the ratio was USD $204,535 per QALY. • The PCV-7 cost per QALY including herd effects was USD $43,275 and for PHiD-10 the ratios were USD $45,100 * Tyo K et. al. Vaccine 29 (2011) 6686– 6694

8. Cost- effectiveness data – Australia* • Potential benefits estimated for PHiD-CV were due primarily to prevention of otitis media and for PCV-13 due to a further reduction in IPD. • At equivalent total cost to vaccinate an infant, compared to no PCV the base-case cost per QALY saved were estimated at A$64,900 (for PCV-7; 3 + 0), A$50,200 (for PHiD-CV; 3 + 1) and A$55,300 (for PCV-13; 3 + 0), resp. • Assumptions regarding herd protection, serotype protection, otitis media efficacy, and vaccination cost changed the relative cost-effectiveness of alternative PCV programs. • The high proportion of current invasive disease caused by serotype 19A (as included in PCV-13) may be a decisive factor in determining vaccine policy in Australia. * Newell AT et. al. Vaccine 29 (2011) 8077– 8085

9. Cost - Effectiveness data – Mexico* • Strategy based on PCV13 prevented 16.205 deaths, gained 332.006 QALYs and saved US$1,307/child vaccinated. • Strategies based on PCV7 or PCV10 prevented 13.806 and 5.589 deaths, gained 282.969 and 114.972 QALYs & saved US$ 1,084 and US$ 731/child vaccinated, resp. • These results were robust to variations in herd immunity and lower immunogenicity of 10-valent vaccine. • Conclusion: Strategies based on 7, 10 & 13-valent PCVs would be cost-saving interventions, with highest health outcomes and savings of the strategy based on 13-valent vaccine. * Mucino-Ortega E et. al. Value in Health (2011) S65 – 70

10. Cost-effectiveness – Valencia (Spain) * • Universal PCV-13 vaccination would decrease the no. of hospital admitted pneumonia by 4571 cases while avoiding 310 cases of IPD and 82,596 cases of AOM throughout the cohort lifetime. • A total of 190 S. pneumoniae related deaths would be averted over the same period. • Total medical costs of non-vaccinating the cohort of newborns would reach up to € 403,850.859 compared to € 438,762.712 for vaccinating the cohort. • The incremental cost of vaccinating the children was estimated in € 12,794 per QALY. • Conclusion: Universal PCV-13 vaccination would be a cost effective intervention for preventing pneumococcal infections and its associated mortality and morbidity. * Diez-Dominigo J. et. al. Vaccine 29 (2011) 9640–9648

11. Burden of disease - recent updates based on review of literature (national & global); • Brief report of any cost-effective analysis published in last 6-12 months; • Clinical trials: ongoing/planned/completed; • New recommendations from other agencies; • Contentious issues, if any.

12. Ongoing clinical trials • COMPAS study • Being conducted in 24,000 children in 3 Latin American Countries; 4 year follow-up • Aim is to study the efficacy in preventing clinical and radiological pneumonia in study group • PCV10 (with NTHi D protein) in study arm with control (Hep. B and Hep. A) • Interim data – vaccine efficacy rate of 22% (clinical pneumonia i.e. features of LRTI with CRP > 40 mg/L) and 25.7% (Consolidation on X-ray Chest) • Likely to be officially published in March/June 2012

13. Other Efficacy data • PHiDCV (PCV10) introduced in Brazil from 2010 • 1284 children randomly selected from Central Brazil from Dec 2010 to Mar 2011 • Effectiveness of pneumococcal NP carriage for incomplete and completely vaccinated children were 26% (95% CI: 0%-50%) and 36%(95% CI: 12%-53%), respectively. • For CAP, the effectiveness for complete vaccinated children was 40% (95% CI: 1.4%-63%). Andrade AL et al. Presented at WSPID, Melbourne, Nov 2011

14. PCV7 and PCV13 prevents meningitis • Municipality of Campos (Rio de Janeiro) introduced free PCV7 in children under one year old from 05/29/2009, until 10/24/2010, when it was replaced by PCV13. • Primary doses at 3, 5, 7 months, with booster dose at 13 months age. After 19 months of vaccination, at least 6,440 children received 4 doses of vaccine, with 92% of coverage vaccination status (7.000 births/year). • There was no suspect or confirmed pneumococcal meningitis case in 2010, when compared with 2009, when there were notified 5 cases, and 1 death. Kury CM et al. Presented at WSPID Melbourne Nov 2011

15. Acute Bacterial Core surveillance data (US)* • Rates of IPD with all serotypes per 1,00,000 pop. In children < 2 years of age (Total 15980 cases) • Effect of switch to PCV13 in Feb 2010 * P < 0.0001 Conclusion: These preliminary findings are consistent with early effects of PCV13 on IPD among young children *Presented at ICAAC of ASM at Chicago Sept. 2011

16. Burden of disease - recent updates based on review of literature (national & global); • Brief report of any cost-effective analysis published in last 6-12 months; • Clinical trials: ongoing/planned/completed; • New recommendations from other agencies; • Contentious issues, if any.

17. New recommendations for PCV 10 • Iceland – PCV10 April 20111 • EMA(CMPH) – PCV10 June 20112 (extension of use for 2 to 5 year age group) • Brazil, Chile, Mexico, Colombia • Finland, Sweden, Netherlands • Albania, Bulgaria, Austria, Cyprus • Kenya 1. EPI-ICE 7:2 Apr-Jun 2011 2. NELM News Service June 2011

18. New recommendations – PCV10 vs PCV13 • Switch from PCV 10 to PCV 13 • Hong Kong Nov 20111 • Australia Aug 20112 • Canada Sep 20103 • Simultaneous use of PCV10 and PCV 13 • Korea Apr 20114 • No comment of superiority or otherwise of either vaccine • No special recommendation for use of either vaccine in any specific group • New Zealand May 20115 • Use of PCV10 routinely and PCV13 for “high-risk” group 1. Press Release: Health Dept. HK. Nov 29, 2011. 2. Dept. Memo dated 30th Aug, 2011 3. CCDR: Nov 2010. 4. Korean J Pediatr 2011;54(4):146-151 5. IAC – Univ. of Auckland

19. New recommendations – schedules of vaccination • 2 + 1 schedule • Colombia (Bogotá), Finland, Mexico, Sweden (3 provinces) • U.K., France, Belgium • 3 + 1 schedule • Australia (Northern Territories), Austria (high-risk groups), Albania, Brazil, Bulgaria, Cyprus (high-risk groups), Hong Kong, Taiwan  (Taipei), The Netherlands, Germany • 3 + 0 schedule • Kenya N.B. PCV13 now recommended for adults aged 50 years and over

20. Are 2 primary doses adequate? • Review of 8 RCTs on PCV7 in 10 countries • Immunological data: 3p schedules result in slightly higher antibody levels than 2p schedules both before and after a booster dose, particularly for serotypes 6B and 23F. • There is an absence of clinical outcome data • Limited data re: nasopharyngeal carriage from direct comparisons of any 2p to any 3p schedule. P. Scott et al. Vaccine 29 (2011) 9711–9721

21. Burden of disease - recent updates based on review of literature (national & global); • Brief report of any cost-effective analysis published in last 6-12 months; • Clinical trials: ongoing/planned/completed; • New recommendations from other agencies; • Contentious issues, if any.

22. Contentious Issues – Additional categories in high risk group • Prematurity and VLBW babies • Up to 9 fold higher incidence of IPD in VLBW babies compared to full size babies* • Is included as high risk category by many advisory bodies incl. ACIP (USA), New Zealand • IAP COI recommendations 2010 do not include this category as “high-risk” • Need to correct this lacuna in next publication * Shinefield H et al. Pediatr Infect Dis J.2002;21:182-6

23. Thank You