GAVI Vaccine Investment Strategy

1
GAVI Vaccine Investment Strategy

• Japanese Encephalitis Analysis

Final October 27, 2008
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Japanese Encephalitis (JE)
CONTENTS

• Disease Overview
• Vaccine Landscape
• Vaccination Policy Strategies
• Vaccine Need Adoption Forecast
• Vaccine Cost Analysis
• Implementation-Associated Cost Analysis
• Analysis Summary
• Key Resources

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Disease Overview
JE
DISEASE PATHOGEN, TRANSMISSION TARGET
POPULATION1

• Disease Pathogen
• Japanese Encephalitis (JE) virus is in the
  Flavivirus genus
• Transmission
• Transmitted by Culex mosquitoes (Cx.
  tritaeniorhynchus)
• Aquatic birds, pigs and other animals serve as a
  reservoir, and as an amplifying host
• Geographic Distribution
• Rural populations in Asia and Western Pacific
  Region
• Disease Target Population
• Infants and children up to the age of 15 years
  old are most susceptible to infection

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Disease Overview
JE
DISEASE IMPACT1

• Total Morbidity
• At least 50,000 cases of JE are reported annually
  (12 million asymptomatic cases)
• This is an underestimation of disease incidence
  since incidence rates during outbreaks can reach
  gt100 cases per 100,000 population
• Surveillance data in developing countries is
  limited and under reported
• Total Mortality
• Case Fatality Rates are high (30-35) resulting
  in 15,000 deaths annually
• Epidemic Potential
• Large outbreaks in the summer in parts of China,
  South-East Russian Federation, South and
  South-East Asia (outbreaks can reach gt100 cases
  per 100,000 population)
• Disease Sequelae
• About 50 of cases result in permanent
  neuropsychiatric sequelae
• 30 of survivors have persistent motor deficits
  and 20 have severe cognitive and language
  impairment

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Disease Overview
JE
DISEASE BURDEN GEOGRAPHIC DISTRIBUTION2
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Disease Overview
JE
DISEASE BURDEN IN GAVI-ELIGIBLE COUNTRIES
MORBIDITY3-6
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GAVI Vaccine Investment Strategy Vaccine
Landscape Analysis_Cholera_Apr08
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JE
Disease Overview
DISEASE BURDEN IN GAVI-ELIGIBLE COUNTRIES
MORTALITY4-7
GAVI Vaccine Investment Strategy Vaccine
Landscape Analysis_JE_Apr08
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Disease Overview
JE
NON-VACCINE PREVENTION TREATMENT INTERVENTIONS8

• Non-Vaccine Prevention
• Reduction in cultivation, use of pesticides and
  centralized pig production may help to prevent
  the spread of JE, but there is no proof to
  support these prevention efforts
• Treatment Interventions
• No specific antiviral treatment exists
• Supportive therapy can reduce morbidity and
  mortality
• Mannitol and other medications to reduce
  intracerebral pressure
• Trihexyphenidyl hydrochloride and central
  dopamine agonists are used to treat acute
  extrapyramidal symptoms
• Neutralizing murine monoclonal antibodies are
  reported to improve clinical outcomes as well

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Disease Overview
JE
INEQUITIES

• Inequity of Poor
• Japanese Encephalitis mainly strikes poor rural
  communities in 14 poor countries of Southeast
  Asia and the Western Pacific
• Gender Inequities

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JE
CONTENTS

• Disease Overview
• Vaccine Landscape
• Vaccination Policy Strategies
• Vaccine Need Adoption Forecast
• Vaccine Cost Analysis
• Implementation-Associated Cost Analysis
• Analysis Summary
• Key Resources

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Vaccine Landscape
JE
LICENSED VACCINES
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Vaccine Landscape
JE
VACCINES IN CLINICAL DEVELOPMENT
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JE
Vaccine Landscape
ESTIMATED VACCINE AVAILABILITY
SA14-14-2 Inactivated (Intercell) SA14-14-2
Attenuated (Chengdu) Chimerivax-JE
(Acambis) JE-Vax (Biken) Inactivated P3
(Beijing Inst Biol Prod) BK-VJE (Biken) KD-287
(Kaketsuken)
(gt 9mo)
(adults)
(gt9mo)
(gt9mo)
(adults)
(gt 9mo)
(gt9mo)
Prior to 2009
2009
2010
2011
2012
2013
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Vaccine Landscape Analysis
JE
COST EFFECTIVENESS LITERATURE SUMMARY (I)

• In Vietnam, a hypothetical cohort of 100,000
  neonates vaccinated with inactivated vaccine
  would prevent 117 cases and 12 deaths, save
  51,122 in direct medical costs, save 49 per
  DALY averted and 4,562 per death averted over 30
  years. In the absence of vaccination, over 30
  years, JE in Vietnam is associated with 1,253
  DALYs, treatment costs of 261 (range 116-833)
  per case, and costs related to long-term sequelae
  of 429 per case (range 234-624).13
• In Thailand, the hypothetical cohort of 100,000
  neonates vaccinated with inactivated vaccine
  would prevent 103 cases and 18 deaths, save
  58,776 in direct medical costs, 343 per DALY
  averted, and 30,654 per death averted over 15
  years. In the absence of vaccination, over 15
  years, JE in Thailand is associated with 2,243
  DALYs, treatment costs of 1,209 per case, and
  costs related to long-term sequelae of 675.51
  per case.13

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Vaccine Landscape Analysis
JE
COST EFFECTIVENESS LITERATURE SUMMARY (II)

• A cost-effectiveness analysis of routine
  immunization to control JE in Shanghai, China
  demonstrated that vaccination with P3 vax
  prevented 420 cases and 105 deaths, saved
  614,762 in direct medical costs, -54 per DALY
  averted, and -4,880 per deaths averted. In
  contract, vaccination with live, attenuated SA
  14-14-2 predicted the prevention of 427 cases and
  107 deaths, savings of 626,665 in direct medical
  costs, 78 per DALY averted, and -4,789 per
  death averted. In the absence of vaccination, JE
  in Shanghai is associated with 7,441 DALYs,
  treatment costs of 130 per case, and costs
  related to long-term sequelae of 121 (range
  48-181) per case.14

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Vaccine Landscape Analysis
JE
COST EFFECTIVENESS LITERATURE SUMMARY (III)

• Cost-effectiveness analysis of strategies for
  controlling JE in Andhra Pradesh, India amongst
  1 million 0-15 year olds and 65,000 newborns
  predicted vaccination with MB vax prevented 175
  cases and 36 deaths, 178,558 in direct medical
  cost savings, 1,247 per DALY averted, 106,813
  per death averted. Vaccination with SA 14-14-2
  predicted 316 cases and 65 deaths averted,
  319,627 in direct medical cost savings, 76 per
  DALY averted, 6,472 per death averted. Without
  vaccination, JE infection in this cohort causes
  7,431 DALYs, treatment costs of 133 per case and
  1,070 per severe case.15
• A cost benefit analysis of JE vaccination in
  Thailand using inactivated vaccine estimated that
  124 cases and 31 deaths averted, direct medical
  cost savings of 72,922 in treatment costs,
  disability care and loss of future earnings per
  prevented JE case, and 15,715-21,661 per
  prevented JE case.16

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Vaccine Landscape Analysis
JE
COST EFFECTIVENESS LITERATURE SUMMARY (IV)

• Analysis of JE in Cambodia showed JE to cause
  7,339 DALYs over 10 years, costing 28 (Range
  0-347) (out of pocket only) per case treated.
  The cost-effectiveness of SA 14-14-2 vaccine in a
  2009 population cohort (1-10 yo and 9-mo) over 10
  years, demonstrated that the total cost per case
  treated was 1,660, and loss of earning related
  to long-term sequelae was 154,935-169,878.
  Vaccination prevented 3,099 cases and 403 deaths,
  saved 92,752 in out of pocket medical expenses,
  42 per DALY averted, and 5,093 per death
  averted.17
• Cost-effectiveness analysis of JE vaccine in 14
  GAVI eligible countries (out of pocket cost is
  excluded). Vaccination of a 2009 population
  cohort would prevent 322,131 cases and 71,161
  deaths, 30,971,268 in direct medical cost
  savings (based on WHO CHOICE), 28 per DALY
  averted, and 3,562 per death averted over
  10-years. Without vaccination, JE infection
  resulted in 6,672,947 DALYs and treatment costs
  of 150 per case.18

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JE
CONTENTS

• Disease Overview
• Vaccine Landscape
• Vaccination Policy Strategies
• Vaccine Need Adoption Forecast
• Vaccine Cost Analysis
• Implementation-Associated Cost Analysis
• Analysis Summary
• Key Resources

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Vaccination Policy Strategies
CURRENT POLICY
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Vaccination Policy Strategies
VISP DECISION FRAMEWORK
GAVI VIS Decision Framework
Vaccination Strategies for Financial Planning
Purposes
Routine Vx of infants with 12mo boost and
catch-up campaign in 1-15yo
Offer Vaccine Financing to GAVI-Eligible Countries
Do Not Support in 2009 - 2013
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JE
CONTENTS

• Disease Overview
• Vaccine Landscape
• Vaccination Policy Strategies
• Vaccine Need Adoption Forecast
• Vaccine Cost Analysis
• Implementation-Associated Cost Analysis
• Analysis Summary
• Key Resources

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Vaccine Need Adoption Forecast
GAVI-ELIGIBLE COUNTRY VACCINE NEED
Vaccine Need 14 VISP Scope 13

• JE is the most important form of viral
  encephalitis in Asia (WHO position paper, Aug06)
  Pakistan has also been included based on evidence
  of JE (PATH JE Team)

1 Adopted in 2006 procure directly from
Chengdu will not seek GAVI financing support
BLUE adopted lt 2009
Source WHO PATH JE Team
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Vaccine Need Adoption Forecast
INTEGRATED ADOPTION FORECAST
Vaccine Need 14 VISP Scope 13
Cambodia Indonesia Nepal Sri Lanka
Korea, DPR PNG Timor-Leste Viet Nam
Bhutan Lao PDR
Bangladesh
Myanmar
Pakistan
India
India adoption decision made without GAVI funding
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Vaccine Need Adoption Forecast
VACCINE DEMAND GIVEN INTEGRATED ADOPTION FORECAST
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JE
CONTENTS

• Disease Overview
• Vaccine Landscape
• Vaccination Policy Strategies
• Vaccine Need Adoption Forecast
• Vaccine Cost Analysis
• Implementation-Associated Cost Analysis
• Analysis Summary
• Key Resources

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Vaccine Cost Analysis
ANALYSIS INPUT SUMMARY GENERAL
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Vaccine Cost Analysis
ANALYSIS INPUT SUMMARY STRATEGY-SPECIFIC
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Vaccine Cost Analysis
KEY OUTPUT SUMMARY Integrated Demand
Forecast 2009-2020
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Vaccine Cost Analysis
ANNUAL ANALYSIS RESULTS Integrated Demand
Forecast 2009-2020
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JE
CONTENTS

• Disease Overview
• Vaccine Landscape
• Vaccination Policy Strategies
• Vaccine Need Adoption Forecast
• Vaccine Cost Analysis
• Implementation-Associated Cost Analysis
• Analysis Summary
• Key Resources

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Implementation Associated Cost Analysis
Typical IMPLEMENTATION CHALLENGES
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Implementation Associated Cost Analysis
UNIQUE IMPLEMENTATION CHALLENGES
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Implementation Associated Cost Analysis
POTENTIAL IMPLEMENTATION SYNERGIES
Traditional Routine EPI vaccines includes
Baccillus Calmette-Guérin (BCG),
Diphtheria-tetanus-pertussis (DTP) , measles
containing vaccines (MCV), oral polio (OPV),
Tetanus toxoid (TT)

• Vaccine-Specific Synergies
• Leverages traditional EPI systems for routine
  vaccination component
• Potential to integrate with meningo-encephalitis
  surveillance systems in Western Pacific Region
  and Southeast Asia Region that include Hib and
  pneumo
• Potential to increase immunization coverage by
  co-administration of the CDIBPs live attenuated
  SA 14-14-2 vaccine with measles
• Other Synergies
• No other synergies were identified

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Implementation Associated Cost Analysis
RELATIVE Cost Assessment
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Implementation-Associated Cost Analysis
Quantitative Cost Assessment
WHO GIVS Study Wolfson LJ, Gasse F, et.al.,
WHO, Estimating the costs of achieving the
WHO-UNICEF Global Immunization Vision and
Strategy, 2006-2015, BLT (2008) 86(1)
36
JE
CONTENTS

• Disease Overview
• Vaccine Landscape
• Vaccination Policy Strategies
• Vaccine Need Adoption Forecast
• Vaccine Cost Analysis
• Implementation-Associated Cost Analysis
• Analysis Summary
• Key Resources

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Analysis Summary
KEY METRIC SUMMARY
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JE
CONTENTS

• Disease Overview
• Vaccine Landscape
• Vaccination Policy Strategies
• Vaccine Need Adoption Forecast
• Vaccine Cost Analysis
• Implementation-Associated Cost Analysis
• Analysis Summary
• Key Resources

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Key Resources
EXPERT CONSULTATION

• Product Development Program (PATH JE Vaccine
  Team)
• John Wecker, Global Program Leader, Immunization
  Solutions
• Chutima Suraratdecha, Health Policy Economics
  Officer
• Suppliers
• John-Kenneth Billingsley, Executive Director EU
  International Organizations, Novartis Vaccines
  and Diagnostics
• Mahima Datla, VP Strategic Business Development,
  Biological E
• Martin Götting, VP Marketing Sales, Intercell

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Appendix
JE
REFERENCES (I)

• Weekly Epi. Record, No. 34/35, 2006, 81 331-340
  www.who.int/vaccine research/ diseases/
  vector/en/index1.html Plotkin et al, Chap. 17,
  Vaccines, 5th Edition, 2008.
• CDC, http//wwwn.cdc.gov/travel/yellowBookCh4-Japa
  neseEncephalitis.aspx.
• Morbidity assumes a 30 case fatality rate
  according to PATH JE Program Team,
  www.path.org/projects/JE_in_depth.php.
• Tsai TF, New initiatives for the control of
  Japanese Encephalitis by vaccination Minutes
  of a WHO/CVI meeting Bangkok, Thailand, October,
  2000. Vaccines (2002) 181-25.
• UN Population Division, World Population
  Prospects The 2006 revision population
  database, http//esa.un.org/unpp/index.asp?panel2
  .
• CDC, Risk of JE by country, region and season,
  www.cdc.gov/ncidod/dvbid/jencephalitis/risk-table.
  htm.
• WHO, GBD 2002 Deaths by age, sex and cause for
  the year 2002 (regional deaths),
  www.who.int/healthinfo/bodgbd2002revised/en/index.
  html.
• Plotkin et al, Chap. 17, Vaccines, 5th Edition,
  2008.

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Appendix
JE
REFERENCES (II)

• Plotkin et al, Chap. 17, Vaccines, 5th Ed, 2008
  SA14-14-2 Attenuated is also approved in India,
  Nepal, S. Korea, Thailand and Sri Lanka Safely
  administered with MCV, www.who.int/wer/2008/wer830
  4.pdf.
• JE Vax Package Insert, Sanofi-PastEURO Local
  suppliers NIPM National Institute of
  Preventive Medicine, Guo-Guang (Taiwan)
  http//www.intercell.com/images/content/binaries/d
  59e97b9-3f0d-40d8-891f-139bcdbdd190.pdf GPO
  Government Pharmaceutical Organization
  (Thailand) NIHE National Institute of Hygiene
  (Vietnam).
• Intercell AG Press Release, 16Jul07
  ClinicalTrials.gov/show/NCT00596102.
• Acambis starts paediatric trial of its
  single-dose JE vaccine in India 25Jan07,
  http//www.acambis.com/default.asp?id1822 CDC,
  www.cdc.gov/VACCINES/recs/acip/downloads/mtg-slide
  s-feb08/32-2-je.pdf.
• WHO SEA/WPRO and PATHs JE Project, Report of the
  bi-regional meeting on JE, Bangkok, Thailand,
  30Mar-1Apr05.
• Ding D, Kilgore PE, Clemens JD, et al
  Cost-effectiveness of routine immunization to
  control Japanese encephalitis in Shanghai, China,
  Bull WHO 2003 81334-342.

42
Appendix
JE
REFERENCES (III)

• Suraratdecha C, Jacobson J, Sivalenka S, Narahari
  D, J Pharma Finance, Econ Policy. 15(1)21-40,
  2006.
• Siraprapasiri T, Sawaddiwudhipong W, Rojanasuphot
  S SE Asian J Trop Med Pub Hlth, 1997
  28143-148.
• Presentation at the Information Sharing Meeting
  on New Vaccines in Cambodia, March 27, 2008,
  Cambodia.
• Presentation at the GAVI Alliance, October 7,
  2007.