Seth Berkley, MD President, CEO, and Founder

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

http://www.iavi.org/

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



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


Pharmaceutical companies,product-development partnerships

Filling the gap in AIDS vaccine R&D

Basicresearch

Appliedresearch


Clinicaldevelopment

Advanceddevelopment


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


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%



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

http://www.thsti.org/default.htm

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



Biotech companies Pharmaceutical companies

Traditionally, a continuum of players moves new drugs to market

Basicresearch

Appliedresearch


Clinicaldevelopment

Advanceddevelopment



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%



A vast improvement overall. . .


R&D DELIVERY ERADICATION

Goals for the Decade…



Achieving universal coverage

Finishing the job

Seth Berkley, MD President, CEO, and Founder

Documents

global immunization

developing countries

global child mortality

child deaths

developed countries

highincome countries

immunization coveragelow

gavi eligible lics