1. The Pneumococcus Challenge
Dr. Orin Levine, Executive Director
GAVI’s PneumoADIP at Johns Hopkins
&
Dr. Samba Sow
Centre pour le Développement des Vaccins, Mali
Second Meeting of the AMC Technical Working Group
HM Treasury, London
9 November, 2006

2. Overview Pneumococcal disease burden Vaccines
Obstacles to wide use in developing countries
How an AMC for pneumo helps

4. Pneumococcal Disease Global Overview
Serious. Up to 1 million child deaths each year. Survivors of meningitis are often left with life-long disabilities.
Common. The No. 1 cause of vaccine-preventable mortality.
Preventable. Global formulation vaccines by 2009.

5. Pneumococcal diseases
The Bacterium
Streptococcus pneumoniae
Serotypes (i.e., strains)
9-13 cause ~80% of pediatric disease worldwide
The Diseases
Pneumonia
Meningitis
Sepsis (bloodstream infection)
Ear infections (a.k.a. otitis media)

6. Leading infectious killers
Pneumonia
3.5
S. pneumoniae:
~1.6 million deaths, including ~800,000 child deaths
3.5
< 5 years old
> 5 years old
3.0
AIDS
2.7
Diarrhoea
2.2
2.5
Deaths (millions)
2.0 TB
1.7
1.5
Malaria
1.1
1.0
0.5
Source: WHO

7. Pneumonia: Leading child killer
Deaths
Pneumonia deaths are about 25% of all child deaths
Illness
151 million pneumonia cases each year
13-20 million are severe enough to require hospitalization
Causes
Pneumococcus is the leading cause of child pneumonia deaths (~40%)
About 1 in 10 child deaths due to pneumococcal disease
CONCLUSIONS:
Reaching MDG 4 for child survival requires pneumonia prevention.
Pneumococcal disease especially important target.

8. Child pneumonia deaths are concentrated in Africa and Asia

9. Pneumococcal disease requires urgent prevention effort
HIV increases risk times
Antibiotic resistance makes cases harder to treat
Pneumococcal pneumonia follows pandemic influenza
Additional ~4.5M pnc pneumonia cases and 450,000 deaths expected in children in GAVI countries

10. Developing country perspective on pneumococcal disease

11. HIV & pneumococcal disease in South Africa
Pneumococcus is the most common cause of bacterial pneumonia in HIV infected individuals
Pneumococcal burden doubled btwn
Mirrors HIV epidemic in children
6% of babies born are HIV infected but account for 75% pneumo disease in children
Cases / 100,000 infants / year
Source: Karstaedt A, et al Pediatric Infect Dis J 2000

12. 14% of child deaths in hospital are due to pneumococcal disease
Bamako, Mali
8-month old girl: quick death due to pneumococcal meningitis
Child sick for 3 days: irritability, vomiting, fever
Parents took child to nearby community health center where treated for presumed malaria
Next day, child had seizures, got worse
Parents took child to hospital
Pediatrician suspected meningitis or severe malaria
Child dies at hospital while father goes to buy antibiotics
Courtesy Dr. Samba Sow, CVD-Mali

13. Pneumococcal conjugates protect the most vulnerable populations
High efficacy in 7 randomized trials in Africa, Asia, Europe, US
Includes 7-valent, 9-valent, and 11-valent formulations
>30M children safely, effectively vaccinated with 7-valent
Gambia Trial: Shows pneumococcal vaccination saves lives
7.4 deaths prevented for every 1000 children vaccinated
Proven efficacy in children with HIV and in high malaria areas.
- When conjugate vaccines were tested in Africa, it was also shown to be safe and effective.
- (read next 2 bullets)
- These studies were done in populations representative of much of the world’s poorer populations - in children from high malaria endemic areas and in children with HIV.
- But why, if this is such a good vaccine, have we not introduced it into these pops who need it most?

14. Pnuemococcal vaccines can help achieve MDGs and reduce poverty
Reducing under 5 mortality
by 7 deaths per 1000
children vaccinated
Preventing
meningitis
with >85% efficacy
Reducing hospitalizations for serious
illness by ~15% and the long-term
costs of caring for disabled survivors
MDG 4 – Child Mortality
MDG 1 - Poverty
Immunization
Improved
Health Outcomes
Poverty Reduction
HIB Vaccines will also achieve the same goals and should also be implemented to help achieve MDGs
Improved
Educational Outcomes
Preventing hearing loss
by reducing ear tube
surgeries by 20%
MDG 2 – Primary Schooling

15. The Challenges

16. Introducing new vaccines is like driving in the Australian outback…it requires planning for emergencies way in advance

17. These problems are not new for pneumococcal vaccines
These problems are not new for pneumococcal vaccines. This has been evident with HepB, a relatively cheap vaccine, and with Hib.
If we do business as usual, years will pass before pneumococcal vaccines are available to the poorest countries.
It took over 17 years from when HepB vaccine was first introduced into Industrialized countries before it reached even 10% of GAVI-eligible countries, and only after 21 years was coverage over 50%.
Historically years passed before new vaccines reached poorest children
ESTIMATE
Million doses
HepB – 75 lowest income countries
50% coverage**
50% coverage**
33% coverage**
Hib - 75 lowest income countries
10% coverage** 1 3 5 7 9 11 13 15 17 19 21 23
Years from availability to introduction

18. Breaking the “Vicious Circle” Accelerated Development & Introduction Plan (ADIP)
2) Limited vaccine supply keeps prices relatively high
Limited supply
Higher
price
Uncertain
demand
3) Higher prices keep developing countries uncertain about demand
1) Uncertainty about demand in developing countries leads industry to limit investments in capacity

19. Challenges to developing and introducing pneumo vaccines
Disease burden, vaccine efficacy data
GAVI’s PneumoADIP, WHO, researchers, others
Systems constraints for delivery
GAVI Health Systems funding, National budgets, others
Vaccine formulations for developing countries
Vaccine supply may not be available at the time of demand
Sustainable, affordable pricing

20. Current vaccines and leading candidates

21. Proportion of pediatric pneumococcal disease prevented by vaccination
86%
60%
71%
62%
38%
73%
10v and 13v are global formulations
7-valent
10-valent
13-valent
88%
81%
84%
66%
92%
87%
89%
73%
86%
Hausdorff systematically reviewed the available data from surveillance in all countries world wide.
This analysis indicated that Asia had the lowest proportion all invasive pneumococcal disease in children preventable by vaccination with 7-valent vaccine (38%)
Latin America and Africa were 60% and 62%, respectively.
Based on Hausdorff et al, the 10- and 13-valent vaccine formulations are expected to include 80-90% of disease in all regions except Asia, where the formulation’s coverage would increase to 66-73%.

22. Pneumococcal vaccine pipeline

23. Key points Global formulations expected between 2009-2010
Supply will come from 2 manufacturers
Both vaccines expected to provide high efficacy and impact in developing countries

24. Vaccine supply & demand
High and middle income country potential demand ~145M doses per year
GAVI forecasted demand ramps to ~56M doses in 2015
Supply
Excess of current capacity is adequate for GAVI forecasted demand until 2011
GAVI demand will outstrip global supply by ~2012

25. Industry feedback Supportive of AMCs Op-Ed in Financial Times
IFPMA press release, “The industry also urges OECD government donors to commit to fund the AMC pilot project. This should provide a strong financial incentive for the development of effective, modern vaccines …. Pneumococcal disease is also a good choice for a pilot project as many companies are active in this field and a number of candidate vaccines are well advanced in development. The IFPMA hopes that future AMC projects will address other disease areas, including those for which candidate vaccines are less well advanced.”

26. Industry feedback Typical comments
“No way to make the major capacity investments needed to supply GAVI volumes without financing commitment to buy the vaccines”
“Need to sustain efforts to build demand for the vaccines”
“Conceptually supportive but devil is in the details”
“Better to have an AMC than not to have this funding at all.”

27. Expected industry responses
Increased capacity investments
Formulation and presentation changes
MNCs - emerging market supplier partnerships (?restart dormant programs?)
Emerging market suppliers prioritize internal projects
Next generation vaccines get a boost

28. Country demand Strong, latent demand for pneumococcal vaccine
Good disease recognition
Success with the vaccine in USA, Canada, Australia, Europe
Convincing clinical trial data
WHO recommendation expected by Q1 2007
Barriers to demand
Preference for vaccine containing serotypes 1 and 5 (these are not in the 7-valent)
Preference for multi-dose vials
Concerns over duration of financing and long-term price

29. Expected country responses
Expressed demand for pneumococcal vaccines
Accelerated use to meet MDG4 goals
Because of better formulation, longer financing, predictable pricing

30. A Pneumo AMC will… Accelerate supply and demand changes…
that will save lives faster than ever before…
by the use of better vaccines…
with sustained financing…
and predictable pricing.

31. Thank you. Visit www. preventpneumo
Thank you. Visit for more information about pneumococcal disease and vaccines.

32. Source: Pneumonia: The Forgotten Killer. WHO/UNICEF