AIDS Vaccines
Advancing Development through Innovation
Frans van den Boom
Vice President IAVI European Programmes
24 October 2007
Helsinki, Finland
Understanding global inequalities
2
Private health spending
Malaria cases
Dorling D (2007) Worldmapper: The Human Anatomy of a Small Planet. PLoS Medicine 4(1)13-18
Global, neglected and most neglected diseases (WHO
& MSF)
3
Most neglected diseases
(e.g. dengue, Chagas)
World pharmaceutical market
(>$600 bn in 2005)
Neglected diseases
(e.g. AIDS, malaria, tuberculosis)
Global diseases
(e.g. measles, diabetes)
Consequently in the last 30 years <1% of the
developed drugs were for LDC specific
diseases
R&D for neglected diseases: PPPs are
changing the field
• PPPs currently manage ¾ of neglected disease drug
development projects
• The private sector is making more independent investments in
neglected disease R&D
A quarter of neglected-disease R&D is now being undertaken
independently by large companies
Four large pharma companies have founded formal neglecteddisease divisions since 2000
Source: Moran (2005) A breakthrough in R&D for Neglected Diseases: New Ways to Get the Drugs
We Need. PLoS Medicine 2(9):e302.
Why do we need New Prevention Technologies?
Our tools today are not enough to stop AIDS
Over 39,5 million people infected with HIV and
11,000 new infections daily
A comprehensive response is needed:
Deliver for today – better use of tools
Prevent further spread of the virus
Treat and care for those already infected
Mitigate social impacts
Develop better tools for the future
Invest in innovation for new technologies
(drugs, diagnostics, microbicides, vaccines)
Better prevention tools – particularly AIDS vaccines - are
critical for the affordability and sustainability of our
commitments to universal access
Source: UNAIDS 2006
Photos: WHO/UNAIDS
A vaccine could save millions of lives
New adult HIV infections in low- and middle-income countries
5
New Infections (Millons)
4
Total new infections
averted by an AIDS
vaccine between
2015-2030
Vaccine introduction
Base
3
Low scenario
30% efficacy,
20% coverage
5.5 million
Medium scenario
50% efficacy,
30% coverage
17 million
High scenario
70% efficacy,
40% coverage
28 million
2
1
0
2000
2005
2010
2015
2020
IAVI impact forecasting; Policy Brief #10, November 2006
2025
2030
Who needs an AIDS vaccine?
All those who are at risk of HIV infection
Especially people in the countries that are hit hardest by the AIDS
epidemic
Especially women, who need tools that they can control to protect
themselves
Especially teenagers and young adults, before they are sexually
active or initiate the use of intravenous drugs
Global demand for an AIDS vaccine could reach
80 million doses per year*
IAVI demand forecasting; Policy Research Working Paper # 15, 2007
What is happening across the AIDS
vaccine field?
Around the world, 23 countries are conducting AIDS vaccine
trials (around 30 vaccine candidates in development)
AIDS Vaccines in Clinical Trials - 2007
Viral Vectors- Adenovirus
DNA vectors
Clade C,
IAVI-ADARC
Ad-5 (Clade B)
Merck
Clade B-minigenes
Epimmune
Ad-5 (Clades A,B,C), [DNA]
NIH-VRC
Clade B-nuclear anchor
FIT Biotech
Ad-6 (Clade B)
Merck
Clade B, MVA*
GeoVax
Viral Vectors- Pox
Multiclade-A,B,C, Ad5*
NIH-VRC
Canarypox (Clade B/E), gp120*
Aventis
Clade B- Micro particle, gp140*
Chiron
MVA (Clade C)
IAVI-Therion
Multiclade, gp120*
U. Mass
MVA* (Clade C)
IAVI-ADARC;
Multiclade-ABC, MVA*
Karolinska
MVA (Clade B),[fowlpox]
Therion
Clade C
Johns Hopkins
MVA (Clade B),[DNA]
GeoVax
Clade B’?C
Changchun Baike MVA (Clade A/E), [DNA]
Clade B/C, NYVAC*
EuroVac
MVA (Clade B’/C
Changchun Baike
Clade B- IL12, IL-15, peptide*
Wyeth
Fowlpox (Clade B)[MVA]
Therion
NYVAC (Clade C)[DNA]
EuroVac
[ ] = prime
Vaccinia (Cocktail)
St. Jude’s
* = boost
Viral Vectors- Other
WRAIR
VEE (Clade C)
AlphaVax [formerly IAVI]
AAV-2 (Clade C)
IAVI-TGEN
AIDS Vaccines in Preclinical Pipeline - 2007
In trials 2007-2009
Ad 35 prototype
NIH-VRC
Ad 35
IAVI-Crucell
Chimeric Adeno
Harvard-Crucell
VSV
Wyeth
Measles
GSK
MVA
SAAVI; WRAIR
NIAID/CHAVI
Chimeric Adeno Vectors
BCG
VSV
CAVD BMGF
Adeno: Chimeric and Ad-11
Pox: NYVAC, MVA
Low sero-prevalent AAV
Reovirus
Newcastle Disease
HIV/VEE Chimeras
HIV/VSV Chimeras
BCG
IAVI Vector Program
Blue = IAVI program
Sendai
CMV
Simian Adeno (GSK)
The current pipeline is inadequate
Only hypothesis currently tested in pipeline is cell-mediated immunity
Political commitment is improved
"Whether it takes us 15 years, 20
years, 25 years to get an AIDS vaccine,
it is what will break the back
of the disease."
- Melinda Gates
More resources are being invested …but more still are
needed, especially from Europe
Investment in AIDS vaccine R&D
Total over 2005 = US$759 mn
Philanthropic
Sector
US$12 m n
Com m ercial
Sector
US$75 m n
Non-US
Public Sector
US$98 m n
US Public
Sector
US$574 m n
Annual average by country relative
to national wealth (2003-2005)
% of GDP
(x10-3)
Country
4.0 – 5.0
United States
3.0 – 4.0
(none)
2.0 – 3.0
Ireland
1.0 – 2.0
0.5 – 1.0
< 0.5
Canada
South Africa
Netherlands
Norway
Denmark
United
Sweden
Kingdom
Australia
India
Brazil
Italy
China
Japan
Finland
Russia
France
Germany Thailand
Based on a 2006 study by the HIV Vaccines and Microbicides Resource Tracking Working Group; full report available
at: www.hivresourcetracking.org. The study reviewed national, not sub-national or provincial, public sector data.
Cuba is not captured as no GDP data is available. Estimates of 2005 investment include NIH CHAVI funds.
Developing a high-quality medicine is a complex
and expensive road
Registration
Clinical Data
Analysis
$
Full
Development
in 100-300
$ $Studies
Patients (Phase II)
Candidate Medicine Tested in
3-10,000 Patients (Phase III)
$
$
$
$
Large Amounts of
Candidate Medicine
Synthesized
Extensive
Safety
Studies
$
Candidate
Studies in Healthy
Volunteers Phase I
$
Exploratory Development
Project Team
and Plans
Formulations
Developed
Early
Safety
Studies
Synthesis
of Compounds
Screening
Discovery
$
What is IAVI’s role?
IAVI’s mission is to ensure
the development of safe, effective,
accesible, preventive HIV vaccines for
use throughout the world
IAVI, public–private product development
partnership since 1996
Political will
& finance
R&D
Clinical
trials
Production
Access &
Health &
other systems uptake
Research and development
Fill the gap between between public sector basic research and commercial product
development
Develop vaccine candidates, prioritize the most promising ones and move them into
clinical trials
Policy and advocacy
Ensure political and financial commitment
Create a supportive environment for research
Prepare for global access
Engage developing countries
Building capacity for R&D
Contribute to sustainable development of health infrastructure
Involve communities, policy makers, politicians, media
IAVI’s niche in AIDS vaccine R&D
Filling the gap between public sector basic research and
commercial product development
Biotech
Venture Capital
Public Sector
Basic
Research
Small
Animal
Biotech
Pharma
Early
Large
Applied Vaccine
Advanced
Product
Scale
Research Design
Devel.
Devel.
Efficacy
NHP
Phase I Phase IIa Phase IIb Phase III
Preclinical and Clinical Trials
IAVI R&D Resources
•New Technology
Assessment
•Product
Development
Infrastructure
Neutralizing
Antibody
Consortium
(NAC)
Vector Design
Consortium
(VEC)
• Network of
Partner-Sites in
Developing World
•IAVI Human IAVI
Immunology Lab
•Vaccine
Development Lab
Control of HIV/
SIV-Live Attenuated
Consortium (LAC)
A global R&D network, with a particular focus on
developing countries
Partnership with developing countries
IAVI’s clinical trial network
IAVI India
Pune-NARI, India
Entebbe-MRC, Uganda
Masaka-MRC, Uganda
Kangemi and KNH-KAVI,
Kenya
IAVI East Africa
Kilifi-CGMRC, Kenya
Kigali-PSF, Rwanda
Lusaka-ZERHP,
Zambia
Cape Town-DTHC,
South Africa
Medunsa, South Africa
IAVI Southern Africa
Soweto, South Africa
Chennai-TRC, India
Product Development: Prioritization of Candidates
DNA
Oxford
2mg
DNA
ADARC
3X4mg
DNA
VRC
3X4mg
AAV
TGC
1x1011
MVA
Oxford
5x107
MVA
ADARC
2.5x108
MVA
Therion
2.5x108
Adeno
VRC
1x1010
92%
46%
Percent Positive Responders
6%
17%
49%
20%
5%
62%
Geometric Mean: SFC/milion and Range of Responses
35
69
109
130
57
130
80
101
31-40
66-73
44-598
54-385
41-79
55-275
39-193
52-297
IAVI has 13 clinical trials completed; 4 clinical trials ongoing
Total of 907 volunteers enrolled in PI and PII trials in 11 countries
Vaccine response rate in vaccinees at peak post vaccination timepoint per trial; Core Laboratory generated data;
GMT SFC and min max SFC for responders; background subtracted per 106 PBMCs.
IAVI Clinical Research Studies:
Prepare for Efficacy Trials & Inform Vaccine Design
Protocol
Summary
Status
A
HIV prevalence
Completed: n=6500
B
HIV incidence
4800 enrolled
C
HIV early infection & HIV control
study
> 150 enrolled
D
Laboratory reference ranges
Completed: n= 2400
enrolled
E
PBMC processing logistics
Completed
F
Potential vector seroprevalence
Completed
G
Neutralizing antibodies
Underway
H
Protocol C in vaccine recipients
In development
P Fast, M Price, N Ketter, J Gilmour, etal
The IAVI model:
working with developing countries
Use a “development” approach to R&D
Ensure that vaccines will be available, accessible and used
Ensure sustainable research capacity and knowledge building
Ensure the participation of national stakeholders
Address social and political context related to research in
different cultural settings
Promote national ownership and in-country commitment
Bring their voices to the global call for an AIDS vaccine
Mobilize countries as integral to the process
Supporting strong and well-informed developing country voices
Industrial-style R&D within the context of
sustainable development and social responsibility
An example:
(1) Site development
Uganda Virus Research Institute [BEFORE]
Site of Proposed UVRI-IAVI Lab & Clinic
<#>
UVRI-IAVI Lab & Clinic in Entebbe, Uganda [AFTER]
 Lab/Clinic built
 Laboratory:Validated CMI assays, GLP
training
 Accredited and now BMGF/CAVD
reference lab
 Clinic: Multiple Phase 1 HIV vaccine
trials: Accelerated approval and
accelerated enrolment vs. historical
controls
 Expansion: Field sites doing incidence
and other clinical studies in preparation
for future efficacy trials
<#>
An example:
(2) Training and education
Vaccine Literacy
Education programmes for:
Healthcare workers
Counselors
Community Advisory Board
Community Workers
An Example:
(3) Preparing for vaccine delivery – lessons from HPV
vaccine introduction
HPV vaccines can facilitate
future introduction of AIDS
vaccines – infrastructure and
lessons
Targeting adolescents/preadolescents before they are
sexually active
Challenging the paradigm of
delayed introduction in the
developing world
IAVI and PATH agreed in early
2007 to a collaboration
around PATH’s “HPV Vaccine:
Evidence for Impact” project
PATH and IAVI strategic partnership
Introducing HPV vaccines in the developing world:
bridging reproductive health with the global response to aids
Shared challenges for
HPV and AIDS vaccines
 Targeting Adolescents
 Sexuality and Stigma
Objectives
Country Introduction
 Implementing Research
 Testing Key aspects
 Strengthening Decision-making
 Delivery Strategies
Policy Analysis
 Complex Messages
 Stakeholder Support
 Demand and Financing
 Rapid Introduction
 Women and Reproductive
Health
 Market, supply and demand analysis
 Develop decision-making tools
Global Advocacy
 Coalition building
 Incorporating HPV vaccine in
development agenda
 South-South cooperation
While important progress is being made, equally important
challenges remain
Issue
What it means
 HIV hyper-variability
Scientific
 Immune correlates of
protection are still unknown
 We are tackling a
moving target
 Relevant animal models
lacking
 Need to test in people
 Success will take time
 Clinical trials long and costly
Policy &
Political
 Long term effort requires long
term, high level global
commitment - leading to
action
 Until recently not a
priority; we need
sustained political
support
 Market incentives for industry
activity lacking
 Build private sector
engagement
 Ethical, regulatory, IP issues
 Optimize environment
for safe, ethical trials
 Health systems challenges
IAVI’s Innovation Fund
Your ideas
Our offer
Breakthrough technologies
Seed funding
Novel immunogens e.g. bNAb, host targets
Target novel immune mechanisms e.g.
innate immunity
New delivery modalities e.g. replicating
vectors, mucosal delivery
New ways to address key challenges – e.g.
from systems or computational biology
Technologies that optimize existing
candidates
Adjuvants and formulation
Antigen optimization
Delivery technologies
Prime-boost combinations
“Enabling technologies”
High throughput screening methodologies
High throughput immunogen design
Non dilutive, targeted grants specifically
designated for high-risk/high-reward
technologies not funded through traditional
HIV funding sources; fast approval process
Platform validation
Feasibility of use in HIV vaccine R&D
Accelerated regulatory pathways
Lower risk of investment in early phase
technologies
Opportunity for longer-term collaboration
Funding & partnership over the long haul
IAVI experience (and infrastructure) with
regulatory approval and clinical trials
including in developing countries
IAVI’s public policy research activities
Activity
The ”business case”
Modeling the impact of AIDS vaccines
Analyzing the potential demand for AIDS
vaccines
Supporting R&D
Regulatory and ethical approval for AIDS
vaccine trials
An advance market commitment (AMC)
for AIDS vaccines
Collateral benefits of vaccine trials
The wider context
AIDS and the Millennium Development
Goals (MDG)
Policy research and advocacy on gender
issues
Why are these important?
Accelerate R&D and future
access
 Ensure adequate funding and
human resource capacity
 Enhance global political and
financial support
 Increase private sector and PPP
engagement
 Build national commitment to
AIDS vaccine research
 Build support for trials and future
demand
The road to a vaccine is long … but there are
many achievements on the way, in the South
National policies for
HIV vaccine research
Community and gender
advisory boards
11 clinical labs & sites
in Africa and India
27000 people who
received VCT
Healthcare workers who
received training
 Medical Ethical committees
 Standards of Care for
volunteers
 Education for communities
and journalists
 Voices from the south in the
global arena
And many others …
And in the North
3 scientific consortia
with scientists from
across the world
Resource tracking
Global HIV Vaccine
Enterprise
Political commitment
Innovation Fund
Financial commitment
We need your support …
To ensure that political commitment to AIDS vaccine R&D is
sustained … for as long as needed
To build an supportive environment with the right policies
To raise sufficient financial support for AIDS vaccine R&D
for IAVI and for the field
To address the remaining key scientific challenges
To continue engaging developing countries and build
sustainable capacity for research
With as ultimate aim to accelerate the development of
an AIDS vaccine that is accessible to all who need it
IAVI’s partners in Europe
Industry
- Berna, Switserland
- Crucell, Netherlands
AIDS organisations
- Cobra, UK
- AIDES, France
- GSK Biologicals, Belgium
- AIDS Fondet, Denmark
- Bioption, Sweden
- Aidsfonds, Netherlands
- FIT Biotech, Finland
- Deutsche AIDS Stiftung, Germany
- IDT, Germany
- El Grupo De Trabajo Sobre
- Transgene, France
Tratamientos Del VIH (gTt), Spain
Vaccine
development
Academia
- Finnish AIDS Council, Finland
- Centre d’Immunologie de Marseille-Luminy, France
- HivNorge, Norway
- Imperial College, London, UK
- National AIDS Trust, UK
- Karolinska Institute, Sweden
- Noah’s Ark, Sweden
- SENSOA, Belgium
Advocacy & - Medical Research Council, Oxford, UK
mobilization - St. Georges University of London, UK
- University of Amsterdam, The Netherlands
20
- University of Oxford, London, UK
IAVI gratefully acknowledges the support of our
donors