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

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

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.

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)

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

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.

Child pneumonia deaths are concentrated in Africa and Asia

Pneumococcal disease requires urgent prevention effort HIV increases risk 20-40 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

Developing country perspective on pneumococcal disease

HIV & pneumococcal disease in South Africa Pneumococcus is the most common cause of bacterial pneumonia in HIV infected individuals Pneumococcal burden doubled btwn 1987 - 1997 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

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

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?

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

The Challenges

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

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, 15-20 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 15-20 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

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

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

Current vaccines and leading candidates

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%.

Pneumococcal vaccine pipeline

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

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

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.”

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.”

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

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

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

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.

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

Source: Pneumonia: The Forgotten Killer. WHO/UNICEF