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Realizing the Potential of Global Vaccines. Seth Berkley, MD President, CEO, and Founder. Tuesday, 2 May, 2011 Global Vaccines 202X: Access, Equity, Ethics University of Pennsylvania. Disparity in Global Immunization Rates 1980-1990. Immunization Coverage - PowerPoint PPT Presentation
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Seth Berkley, MDPresident, CEO, and Founder
Tuesday, 2 May, 2011Global Vaccines 202X: Access, Equity, Ethics
University of Pennsylvania
Realizing the Potential of Global Vaccines
Disparity in Global Immunization Rates 1980-1990
Immunization CoverageLow- and High-income countries, 1980-1990
GAVI Alliance 2010, global immunization rates based on DTP3 coverage
“Preventable childhood diseases. . . against which there are effective vaccines. . . are currently responsible for the great majority of the world's 14 million deaths of children under 5 years and disability of millions more every year.”
“Effective action can and must be taken to combat these diseases. . .”
-UNICEF 1990 World Summit for Children
New Commitments, New Mechanisms 1970-1990
WHO Expanded Program on
Immunization
UNICEF Child
Survival Resolution
WHO Standardized Immunization
Schedules
PAHO revolving fund
established
Task Force for Child Survival
1970 1975 1980 1985 1990
Declaration of Manhattan, CVI
Unprecedented Results: 1980-1990
WHO Global and regional immunization profile; 2010
Proliferation of efforts; continued fragmentation – 1980-1990
R&D DELIVERY ERADICATION
WHOWorld Bank
IUNICEF LMICs
Nat’l Research Agencies
Biotechs Rotary
IndustryAcademia UNICEF
WHO
Closing the gap: an unfinished project
Source: GAVI, WHO, Vaccine introduction database
Hib Disease: Global Child Mortality, 2000
Hib and Pneumococcal Global Burden of Disease Study Team 2009, http://www.who.int/nuvi/hib/GBD_Hib.pdf
R&D DELIVERY
WHOWorld Bank
ERADICATION
IUNICEF LMICs
GAVI
Increasing coverage: GAVI Alliance 2000 - Present
New Vaccines
Original EPI
Nat’l Research Agencies
Biotechs
IndustryAcademia
RotaryWHO
BMGF
BMGF UNICEF
Accelerating vaccine introduction and scale-up
FinancingStrategies Partnerships
GAVI Alliance, 2010, based on WHO data from 2008
Number of manufacturers and price decline of pentavalent vaccine (DPT, Hib, Hep B)
Source: UNICEF Supply Division, 2010
Increased competition reduces vaccine price
Source: UNICEF Supply Division; CDC
Tiered Pricing
R&D for Global Health Prior to PDPs
1975-1997Of 1,123 drugs on the global market between 1975-1997, only 13 targeted tropical diseases, representing 1.1% of all drugs developed.
2009 PDPs had nearly 150 biopharmaceutical, diagnostic and vector control candidates for neglected diseases in various stages of development, including 32 in late-stage clinical trials.
Source: Access to Essential Medicines in Poor Countries: A Lost Battle? Bernard Pécoul, MD, MPH; Pierre Chirac, PharmD; Patrice Trouiller, PharmD; Jacques Pinel, PharmD JAMA. 1999;281:361-367.
Drugs for neglected tropical
diseases,1.1%
Drugs targeting all other
disease types,98.9%
Drugs on the Global Market1975-1997
1986 ’87 ’88 ’89 1990 ’91 ’92 ’93 ’94 ’95 ’96 ’97 ’98 ’99 2000 ’01 ’02 ’03 ’04 ’05 ’06 ’07 ’08 ’091986 1989 1990 1996 1998 1999 2000 2001 2002 2003 2005
Selected otherpublic-private partnershipsWorking on health issues
1977
Strengthening the Pipeline: Product Development Partnerships (PDPs)
Source: Joint United Nations Programme on HIV/AIDS
In 2009, 33.3 million people living with HIV worldwide
7,100 new HIV infections daily; 2.6 million per year
For every 1 person put on treatment, 2 people become infected
30 million AIDS-related deaths to date
260,000 children die of AIDS every year
200933.3 million
28.5 million2000
32 million2005
7.5 million people living with HIV
1990
• Introduction of anti-retroviral therapy
• 20 million people living with HIV
1996
First cases of AIDS
1981
HIV discovered as the causal agent
1984
The need for an HIV vaccine
We need to fully scale-up current strategies and develop new prevention
technologies
Unprecedented momentum in the HIV vaccine field
VACCINES AIDS vaccine shows first
efficacy in clinical trials
Replicating viral vector effective in controlling SIV in animal studies
More than 15 new broadly neutralizing antibodies and their targets on HIV discovered
Efficacy Trials Completed 2003 VaxGen: gp 120: No efficacy 2007 Merck: Ad 5-gag-pol-nef: No efficacy
2009 Sanofi + VaxGen: ALVAC + gp120: ~30% efficacy
Efficacy Trials Underway NIH-VRC: DNA + Ad-5: started 2009, results 2013++
The AIDS Vaccine Pipeline; where are we today?
www.iavi.org
Other Candidates Currently in Clinical Trials Phase II: Range of Cellular immunity candidates Phase I: Range of Cellular immunity candidates
Efficacy Trials Planned IAVI/NIH/BIDMC/HVTN/Crucell: AD26 + AD35: planned 2013 MHRP/NIH/BMGF: RV-144 F/U: Poxvirus + Protein Boost: planned 2014
Early positioning in AIDS vaccine R&D
Basicresearch
Appliedresearch
Preclinical development
Clinicaldevelopment
Advanceddevelopment
Large-scaleEfficacy trials
Public sector, academia
Biotech companies Pharmaceutical companies
A well-established continuum of players moves new drugs to market
Basicresearch
Appliedresearch
Preclinicaldevelopment
Clinicaldevelopment
Advanceddevelopment
Large-scaleEfficacy trials
Public sector, academia
IAVI initially worked to ensure a vaccine for the developing world by focusing on product development
Biotech companies, pharmaceutical companies
AdvocacyClinical trial network in developing worldGap-filling science
Public sector, academia
Pharmaceutical companies,product-development partnerships
Filling the gap in AIDS vaccine R&D
Basicresearch
Appliedresearch
Preclinicaldevelopment
Clinicaldevelopment
Advanceddevelopment
Large-scaleEfficacy trials
But as product failures forced big players out or moved them downstream,a development gap grew …
… and IAVI moved to fill the void, creating new programs as needs arose
Human Immunology Lab (2001)
Neutralizing Antibody Consortium (2002)
Live Attenuated Consortium (2006)
AIDS Vaccine Design and Development Lab (2008)
IAVI Neutralizing Antibody Center at The Scripps Research Institute (2009)
Vectors Consortium (2007)
IAVI Today
Integrated organization that links our …
Industry-style labs and diverse research portfolio
Academic, government and private-sector partnerships
Network of clinical trial centers in Africa and India
Advocacy and outreach from community to international level
IAVI partners around the globe
Neutralizing Antibody Consortium
Vectors Consortium
Live Attenuated Consortium
Innovation Fund grant recipients
IAVI-supported clinical research centers
Other scientific and civil-society partners
IAVI facilities
From HIV Antibodies……. to HIV Vaccine
The purpose: find antibodies that can fight a broad range of HIV strains
How it was done:– 49 research partners in 12 countries– 1800 HIV-positive volunteers– IAVI’s Innovation fund: new technology– 3 state-of-the-art laboratories– 3 biotech companies
The result: Two new antibodies isolated from an African volunteer, more potent than previously seen, that target a new site found on a broad range of HIV strains, including strains from Africa Additional 15 antibodies isolated with new targets Combination of 2 of the antibodies block 99/100 viruses
With new antibodies, new targets
CD4 binding siteb12, VRC01,VRC03, HJ16,PGV04
Source: Schief, W.R. et al.. Curr Opin HIV AIDS. 2009 Sep; 4(5):431-40.
Conserved determinants in theV1/V2 andV3 loopsPG9, PG16
Glycanshield2G12
MPER2F5, 4E10, Z13e1
Mabs from new donors 17, 36 & 39
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
2015
2016
2017
2018
2019
2020
2021
2022
2023
2024
2025
2026
2027
2028
2029
2030
2031
0
5
10
15
20
25
Resources required to respond to the AIDS epidemic in low- and middle-income countries
(US$ Billions)1
Total global investment in AIDS vaccine R&D (US$
Billions)2
US$ Billions
1AIDS 2031 Modeling Working Group, 20102Advancing the Science in a Time of Fiscal Constraint, HIV Vaccines and Microbicides Resource Tracking Working Group, 2010
Total Global Funding for HIV Vaccine Research Relative to the projected cost of the epidemic in LMICs
If current spending trends continued, the annual cost of the AIDS response in LMIC in
2031 would be ~$30billion
Investment in preventive HIV vaccine R&D, 2000–2009
Other public sector
Multilaterals
United States
Europe
Philanthropic
Pharmaceutical, biotech
US$ 800 million
600
400
200
$327$367
$550 $548
$683
$759
$933$961
$868
WORLD TOTAL, 2009:
US$ 868 million
2000 ’01 ’02 ’03 ’04 ’05 ’06 ’07 ’08 ’09
HIV Vaccines and Microbicides Resource Tracking Working Group. Advancing the Science in a Time of Fiscal Constraint: Funding For HIV Prevention Technologies in 2009. New York, 2010
Countries’ public contributions to HIV vaccine R&D compared to their economic size (2007-2009 average, selected countries )
International Monetary Fund, 2010; HIV Vaccines and Microbicides Resource Tracking Working Group, 2010
% of country’s public sector contribution to total global HIV vaccine funding effort
% of country’s portion of global GDP
1980 1990 2000 2010
1980 – 1999: 3 vaccines2000 – 2019: >12 vaccines
HepB(1981)
Hib(1988)
Rota(2004)
HPV(2006)
JE(2009)
Cholera(2009)
Typhoid(~2012)
Malaria(~2014)
rBCG(~2018)
MenA(2009) Dengue
(~2016)
ETEC(~2015)
Shigella(~2015)
DTP-HepB+HibPentavalent Vaccine
(1998)
Pneumo(2000)
Applied Strategies - Project Optimize Vision Workshop, Landscape Overview, June 2010
A revitalized vaccine pipeline HIV, TB(~?)
Reducing the number of total vaccinations against DTP3, Hib, and HepB
Introduction of pentavalent vaccine – 5 vaccines over 3 doses
Lower shipping, injection costs
Partnership model – country MoHs with WHO, UNICEF, and other GAVI partners
Making vaccines more durable Thermostable formulations of a hep B
vaccine and a meningitis A vaccine produced by a spray-drying method
Cold-chain, storage improvements
Not just new, but better vaccines
Kristensen, “Stabilization of vaccines: Lessons learned” Human Vaccines, 2010
Nothing better illustrates the benefits of secure, long-term funding than the pentavalent vaccine, which immunises children against diphtheria, tetanus and pertussis, hepatitis B and Hib.
A vast improvement overall: 1990-2008Immunization CoverageLow- and High-income countries, 1990-2008
GAVI Alliance 2010, global immunization rates based on DTP3 coverage
1990 2009 Change 1990-2009
Global population 5,275,431 6,808,999 +29%
Diptheria Cases 23,864 857 -96%
Measles Cases 1,374,083 222,318 -84%
Pertussis Cases 476,374 106,207 -78%
Polio Cases 23,390 1,779 -92%
Tetanus Cases 64,983 9,836 -85%
Unprecedented Results: 1990-2009
WHO Global and regional immunization profile; 2010
Source/credits: WHO/UNICEF coverage estimates 1980-2009, July 2010
Global number of under-five children unimmunised with 3 doses of DTP
But over 23 million children still unimmunised
India: Reaching universal coverage Vaccine coverage disparities between regions:
Average for India for 2005-2006: 44% of children fully immunized by 24 months
Range for all Indian states in that year: 21%-81%
National Family Health Survey, India, 2007 (most recent available figures)
1988
2009
Progress in Global Polio Eradication; Still Endemic in India…
Today, India is one of four remaining Polio endemic countries As of April 19th, 2011, there has only been one reported case of Polio in India this year
http://www.polioeradication.org/Dataandmonitoring/Poliothisweek.aspx
Shantha Biotech – focusing on inexpensive HepB vaccine • Leveraging local leadership and talent, with cross sectoral partnerships (pharma, WHO, NIH)
• Balance between local health impact and financial returns
Health success – Shanvac-B (Hep B vaccine)• Lowered price, increased uptake
• Scientific success • WHO Prequalification• Quality validation
• Financial success • US$ 340 million contract with UNICEF for pentavalent vaccine• Acquired in 2009 by Sanofi-Aventis for ~US$800 million
India: From producer to innovator
Chakma et al, “India’s billion dollar biotech” - Nature Biotechnology 2010
THSTI-IAVI HIV Vaccine Laboratory
• A partnership set up to accelerate and advance HIV vaccine research and development expand the NAC program and facilitate development of new generation vaccine candidates
• Vision: Identify candidate immunogens that elicit broadly neutralizing antibody responses against HIV-1 by establishing an innovative discovery program employing high throughput technology
Broadly neutralizingantibodies
Determining structure of
novel antigens
High-throughput immunogen
design
Assays to rapidly screen immunogens
Characterize sera and
identify broadly neutralizing monoclonal antibodies
Structuralbiology
Immunogen design
Immunogen screening
Clinical development
Protocol G High-throughput
robot
• NAC Center, TSRI• Innovation fund• Design Lab, NY
• DBT-IAVI • Indian Medicinal
Chem.• THSTI-IAVI HIV
Vaccine Lab
A Call for the Decade of Vaccines
Call to governments, private sector to partner
Committed $10 billion over 10 years
Efforts for vaccine discovery, development, delivery
Potential to save 8 million child lives by 2020 with existing vaccines
Significant, but not sufficient investment
April 11, 2011
Decade of Vaccines Collaboration Organizational Structure
April 11, 2011
Vaccine uptake
and lives saved
• Policymaker attention• Funding
• Advocacy• Demand creation• Evidence base
• Technical consensus• Policy roadmap• Delivery• Evidence base• Financing mechanisms
From ‘Call’ to ‘Action’: everyone has a role
• R&D, manufacturingcapacity
• Technical expertise• Affordable pricing
• Development of vx candidates• Technical expertise
• Commitment to increasing uptake and access
• Sustainable funding
Decade of Vaccines slide, April 11, 2011
Realizing the promise of vaccines over the next decade...
Develop financing mechanisms that span the entire
continuum
Create mechanisms that
allow for rapid information flow
between both ends of the
vaccine continuum
More robust involvement of
low- and middle-income countries
VACCINE AVAILABILITY
PRIC
E
COUN
TRY
PRO
CURE
MEN
TEXTERN
AL RESOURCES
Factors Affecting Vaccine Availability
Factors Affecting Vaccine Availability
Examples of Innovative Financing Mechanisms
International Financing Facility for Immunization (IFFIm)• Funds GAVI Alliance through sale of donor-backed bonds
Advanced Market Commitment• Incentivizes development, manufacturing of pneumococcal vaccine for the
developing world by guaranteeing a market through donor commitments.
Currency Transaction Levy (Robin Hood Tax)• Would provide “billions” to unspecified global health and development
activities through a small tax on currency transactions.
Health Impact Fund• Would offer firms the option to be rewarded according to a product’s health
impact, if they agree to sell it at cost.
Existing
Proposed
DELIVERY
WHOWorld Bank
ERADICATION
IUNICEF LMICs
The ideal vaccine continuum
R&D
GAVI
Industry
Donor Countries
PDPs
Emerging Economies
Foundations
Accelerating the pipeline
Achieving universal coverage
Finishing the job
Rotary
CSOs
• EXTRA SLIDES
A long-term investment: Vaccines take decades to develop
Measles
Hepatitis B
Human papilloma virus(cervical cancer)
Rotavirus(diarrheal disease)
Varicella zoster(chickenpox)
Pertussis(whooping cough)
Polio
Haemophilus influenza
Typhoid
Malaria
Human immunodeficiency virus(HIV/AIDS)
INFECTIOUS AGENT (Disease)
AGENT LINKEDTO DISEASE IN …
VACCINE LICENSEDIN U.S. IN …
1953
1965
1884
1973
1953
1906
1908
1889
Early ’80sto mid-’90s
1893
1983
1963
1981
2006
2006
1995
1948
1955
1981
1989
—
—
YEARSELAPSED
10
16
12-25
33
42
42
47
92
105
118
28
A vaccine would give millions new hope
Source: IAVI calculations
2.5 million
2000 2005 2010 2015 2020 2025 2030
2.0
1.5
1.0
0.5
The world today: New adult HIV infections in low- and middle-income countries are projected to stabilize—but not decline
The future: What would happen if a safe, effective, widely accessible vaccine were introduced? 50% effective,
30% coverage
70% effective, 40% coverage
5.6 million
9.8 million
LOWIMPACT
MEDIUMIMPACT
HIGHIMPACT
Cuts infections 30%, available to 20% of population
Vaccine effectiveness
2.1 million
New infections prevented by 2030
90% effective, 40% coverage
12.0 millionVERYHIGHIMPACT
The potential cost-savings
IAVI/Futures Institute 2009. Estimating the Potential Impact of an AIDS Vaccine in Developing Countries, Marzetta et al 2010. “The potential global market size and public health value of an HIV-1 vaccine in a complex global market”
Average lifetime cost of ART for
one person$7,400
One infection averted by a vaccine means one person who will
not need ART
10000 2000 3000 4000 5000 6000 7000
HIV Vaccine (maximum price at which vaccine
would still be cost-saving)
$25 for 30% effective vaccine$800 for 70% effective vaccine
HPV (developed
world)$360.00 Pneumo
conjugate vaccination
(under AMC) $3.50
Rotavirus vaccine
(GAVI price)$0.30
IAVI’s roleMissionTo ensure the development of safe, effective, accessible, preventive HIV vaccines for use throughout the world
Political willand finance
Research& development
Clinicaltrials
Production Health and other systems
Accessand uptake
Integrated model of R&D• Emphasis on applied research and product
development• Targeting gaps• R&D partnerships with academia and industry
Conducted 25 human trials in 11 countries
Focus Speed Flexibility Willingness to take informed
risk Access is part of our mission
Core principles
Policy and advocacy for the global effort
Sustained commitment to developing countries
200 staff, site workers in Africa, 5 regional offices, active in 25 countries; $100 M annual budget
Evolution of the IAVI model
Basicresearch
Appliedresearch
Preclinical development
Clinicaldevelopment
Advanceddevelopment
Large-scaleEfficacy trials
Public sector, academia
Biotech companies Pharmaceutical companies
Traditionally, a continuum of players moves new drugs to market
Basicresearch
Appliedresearch
Preclinicaldevelopment
Clinicaldevelopment
Advanceddevelopment
Large-scaleEfficacy trials
Public sector, academia
From 1996-2000 IAVI focused on clinical development of vaccine candidates for the developing world
Biotech companies, pharmaceutical companies
AdvocacyClinical trial network in developing worldGap-filling science
Why IAVI? The state of the field 15 years ago
No concentrated research efforts dedicated solely to the challenges impeding AIDS vaccine development
No laboratories systematically evaluating and prioritizingAIDS vaccine concepts
No vaccine ever tested for efficacy
Limited vaccine pipeline
Little investment in products by public or private sectors
Little public interest in HIV vaccines
Little attention to vaccine issues specific to high-incidence countries—no African or Asian vaccine candidates
Few vaccine advocates
Engaging Emerging Scientific Powers
SOURCE: IAVI reports; team analysis
▪ Insufficient funding from government
▪ Less competitive than India in generating R&D funds from generics export
▪ Lack of capacity to launch international standard clinical trials
▪ Low capability in designing trials
▪ Multiplicity of gov. agencies
▪ Difficult to transfer technology and to patent bio-tech products
▪ Less competitive than Indian counterpart in terms of export
▪ Public funding growing, but doesn’t target high-risk, high reward approaches
▪ No private-sector engagement
▪ Perception of weak IP protection
▪ Insufficient public funding
▪ Limited venture capital
▪ Research infrastructure needs upgrading
▪ Inadequate training in conducting trials
▪ Lack of facilities with GLP to launch clinical trial
▪ Multiplicity of gov. agencies & fragmented planning
▪ IP laws have not been well enforced in India
▪ Uncertain domestic demand
▪ Highly fragmented R&D sector
▪ AIDS vaccine field not connected to vaccine efforts in other disease areas
▪ Ban on trials of foreign discovered products
▪ Chinese firms not prequalified to export through multilateral channels
▪ Long, cumbersome approval process
Insufficient funding from government
Less competitive than India in generating R&D funds from generics export
Macro trends & funding R&D Clinical trials Registration,
approvalIP & tech transfer
Distribution and export
Global Health R&D is primarily financed through 1-5 year restricted grants:
The Limitations of Current Global Health R&D Funding
Significant gap between need and available $
Susceptible to political and economic flux
Can’t change course as new science emerges
Short-term
UnpredictableInsufficient
Inflexible
Not conducive to long-term project planning
Financing mechanisms that reach farther upstream and accelerate development of highest priority new vaccines, and link these to downstream delivery to enable immediate public health impact are require
1980 2009 ChangeGlobal population 4,424,952 6,808,999 +54%
Diptheria Cases 97,511 857 -99%
Measles Cases 4,211,431 222,318 -95%
Pertussis Cases 1,982,355 106,207 -95%
Polio Cases 52,795 1,779 -97%
Tetanus Cases 114,251 9,836 -91%
Unprecedented Results: 1980-2009
WHO Global and regional immunization profile; 2010
A vast improvement overall. . .
GAVI Alliance 2010, global immunization rates based on DTP3 coverage
R&D DELIVERY ERADICATION
Goals for the Decade…
Accelerating the pipeline
Accelerating the pipeline
Achieving universal coverage
Finishing the job