The Pneumococcus Challenge Dr Orin

The Pneumococcus Challenge • • • Dr. Orin Levine, Executive Director GAVI’s Pneumo. ADIP 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 vaccinepreventable 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 3. 5 S. pneumoniae: > 5 deaths, < 5 years ~1. 6 millionyears old including ~800, 000 2. 2 child deaths 3. 5 Deaths (millions) 3. 0 2. 7 2. 5 2. 0 1. 7 1. 5 1. 1 1. 0 0. 5 0 Pneumonia AIDS TB Source: WHO Malaria Diarrhoea

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

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. 5 M 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 Cases / 100, 000 infants / year • 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 Source: Karstaedt A, et al Pediatric Infect Dis J 2000

14% of child Bamako, Mali deaths in hospital are due to pneumococcal 8 -month old girl: quick death due to disease 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 • >30 M 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.

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 Immunization Preventing hearing loss by reducing ear tube surgeries by 20% MDG 1 - Poverty Improved Health Outcomes Poverty Reduction Improved Educational Outcomes MDG 2 – Primary Schooling

The Challenges

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

Historically 15 -20 years passed before new vaccines reached poorest children ESTIMATE Million doses 50% coverage** Hep. B – 75 lowest income countries 50% coverage** 33% coverage** Hib - 75 lowest income countries 10% coverage** 1 3 5 7 9 11 13 15 17 19 Years from availability to introduction 21 23

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

Challenges to developing and introducing pneumo vaccines • Disease burden, vaccine efficacy data – GAVI’s Pneumo. ADIP, 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 71% 7 -valent 10 v and 13 v are global formulations 86% 38% 62% 60% 73% 10 -valent 13 -valent 84% 89% 92% 88% 73% 66% 87% 81% 81% 86%

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 Demand • High and middle income country potential demand ~145 M doses per year • GAVI forecasted demand ramps to ~56 M 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 Q 1 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 MDG 4 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. Countries Willing To Introduce Industry Willing To Supply Donors/Countries Willing to Finance “Solution space”

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

Source: Pneumonia: The Forgotten Killer. WHO/UNICEF