The Pneumococcus Challenge

Dr. Orin Levine, Executive DirectorGAVI’s PneumoADIP at Johns Hopkins

& Dr. Samba Sow

Centre pour le Développement des Vaccins, Mali

Second Meeting of the AMC Technical Working GroupHM Treasury, London

9 November, 2006

Overview

•Pneumococcal disease burden•Vaccines•Obstacles to wide use in developing countries

•How an AMC for pneumo helps

Pneumococcal DiseaseGlobal 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 killersD

eath

s (m

illio

ns)

< 5 years old > 5 years old

0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

AIDS

2.7

TB

1.7

Malaria

1.1

Diarrhoea

2.2

Pneumonia

3.5

Source: WHO

S. pneumoniae:~1.6 million deaths, including ~800,000

child deaths

Pneumonia: Leading child killerDeaths• 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

179

349

0

50

100

150

200

250

300

350

400

1986-87 1996-97

Source: Karstaedt A, et al Pediatric Infect Dis J 2000

Cases / 100,000 infants / year

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

14% of child deaths in hospital

are due to pneumococcal

disease

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.

Pnuemococcal vaccines can help achieve MDGs and reduce poverty

MDG 4 – Child Mortality MDG 1 - Poverty

MDG 2 – Primary Schooling

ImprovedHealth

Outcomes

Poverty Reduction

ImprovedEducational Outcomes

Immunization

Reducing under 5 mortalityby 7 deaths per 1000children vaccinated

Reducing hospitalizations for seriousillness by ~15% and the long-term

costs of caring for disabled survivors

Preventing hearing lossby reducing ear tube

surgeries by 20%

Preventingmeningitis

with >85% efficacy

The Challenges

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

50% coverage**

Historically 15-20 years passed before new vaccines reached poorest children

Years from availability to introduction

Million doses

HepB – 75 lowest income countries

Hib - 75 lowest income countries

1 3 5 7 9 11 13 15 17 19 21 23

33% coverage**

ESTIMATE

10% coverage**

50% coverage**

Breaking the “Vicious Circle”Accelerated Development & Introduction Plan (ADIP)

Higher

price

Uncertain

demand

Limited supply

1) Uncertainty about demand in developing countries leads industry to limit investments in capacity

2) Limited vaccine supply keeps prices relatively high

3) Higher prices keep developing countries uncertain about demand

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

Vaccines Expected serotype coverage

Stage of Development

Expected Licensure

Wyeth 7-valent

~50% globally with regional variations higher and lower

Licensed; launched in 2000

Registered in >75 countries

13-valent

~80% globally with less variation than 7-valent

Product in Phase 3 clinical testing

2010

GSK 10-valent

~80% globally with less variation than 7-valent

Product in Phase 3 clinical testing

2008

Proportion of pediatric pneumococcal disease prevented by vaccination

86%

60%

71%

62%

38%

73%

88%

81%

84%

81%

66%

81%

92%

87%

89%

87%

73%

86%

7-valent

10-valent 13-valent

10v and 13v are global

formulations

Pneumococcal vaccine pipeline

Multi-nationals

LaunchedClinical Trial

Phase IIIClinical Trial

Phase IIClinical Trial

Phase I

9-valent

7-valent

Prevnar (7-valent)

11-valent

Preclinical stage

Multi-valent conjugate vaccines3+ suppliers

Emerging suppliers

Expected 2008

~20 vaccinesin research/preclinical

stage(includes

conjugate &protein-based

vaccines)

Discontinued

* Based on publicly available information, and data collected by Boston Consulting Group, PneumoADIP, & PATH

Expected 2010

13-valent

10-valent

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

~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.

Countries WillingTo Introduce

Donors/CountriesWilling to Finance

Industry WillingTo Supply

“Solution space”

Thank you.Visit www.preventpneumo.org for more information about

pneumococcal disease and vaccines.

Source: Pneumonia: The Forgotten Killer. WHO/UNICEF