Title: IAVI AIDS Vaccine 2006 Template
1AIDS Vaccines Advancing Development through
Innovation
Frans van den Boom Vice President IAVI European
Programmes 24 October 2007 Helsinki, Finland
2Understanding global inequalities
2
Dorling D (2007) Worldmapper The Human Anatomy
of a Small Planet. PLoS Medicine 4(1)13-18
3Global, neglected and most neglected diseases
(WHO MSF)
3
Most neglected diseases(e.g. dengue, Chagas)
World pharmaceutical market(gt600 bn in 2005)
Neglected diseases(e.g. AIDS, malaria,
tuberculosis)
Global diseases(e.g. measles, diabetes)
4- Consequently in the last 30 years lt1 of the
developed drugs were for LDC specific diseases
5RD 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 RD - A quarter of neglected-disease RD is now being
undertaken independently by large companies - Four large pharma companies have founded formal
neglected- disease divisions since 2000
Source Moran (2005) A breakthrough in RD for
Neglected Diseases New Ways to Get the Drugs We
Need. PLoS Medicine 2(9)e302.
6Why 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
7New adult HIV infections in low- and
middle-income countries
A vaccine could save millions of lives
Total new infections averted by an AIDS vaccine
between 2015-2030
IAVI impact forecasting Policy Brief 10,
November 2006
8Who 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
9So, is an AIDS vaccine possible? Yes !
- AIDS vaccines should
- Protect against HIV infection (sterilizing
immunity) - All routes of transmission, including
intravenous, mucosal - Protect against progression to disease
- Reduction of viral load
- Reduce transmission (infectiousness)
- Infected vaccinees likely to be lower or
nontransmitters
- The immune system is able to
- control or protect against HIV
- Majority of PLW HIV initially suppress viral load
- Examples of populations resistant to HIV
infection (e.g. Kenyan sex workers) - Children of infected mothers
- Non-progressors control infection for many years
- Promising candidates in pipeline
- SIV infection
- Broadly Neutralizing Antibodies
10What is happening across the AIDS vaccine field?
11Around the world, 23 countries are conducting
AIDS vaccine trials (around 30 vaccine candidates
in development)
12AIDS Vaccines in Clinical Trials - 2007
Viral Vectors- Adenovirus Ad-5 (Clade
B) Merck Ad-5 (Clades A,B,C), DNA NIH-VRC Ad-6
(Clade B) Merck Viral Vectors- Pox Canarypox
(Clade B/E), gp120 Aventis MVA (Clade C)
IAVI-Therion MVA (Clade C) IAVI-ADARC MVA
(Clade B),fowlpox Therion MVA (Clade
B),DNA GeoVax MVA (Clade A/E), DNA WRAIR MVA
(Clade B/C Changchun Baike Fowlpox (Clade
B)MVA Therion NYVAC (Clade C)DNA EuroVac Vacci
nia (Cocktail) St. Judes Viral Vectors-
Other VEE (Clade C) AlphaVax formerly
IAVI AAV-2 (Clade C) IAVI-TGEN
- DNA vectors
- Clade C, IAVI-ADARC
- Clade B-minigenes Epimmune
- Clade B-nuclear anchor FIT Biotech
- Clade B, MVA GeoVax
- Multiclade-A,B,C, Ad5 NIH-VRC
- Clade B- Micro particle, gp140 Chiron
- Multiclade, gp120 U. Mass
- Multiclade-ABC, MVA Karolinska
- Clade C Johns Hopkins
- Clade B?C Changchun Baike
- Clade B/C, NYVAC EuroVac
- Clade B- IL12, IL-15, peptide Wyeth
- prime
- boost
13AIDS Vaccines in Preclinical Pipeline - 2007
- 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
- Sendai
- CMV
- Simian Adeno (GSK)
-
In trials 2007-2009 Ad 35 prototype NIH-VRC Ad
35 IAVI-Crucell Chimeric Adeno Harvard-Crucell
VSV Wyeth Measles GSK MVA SAAVI WRAIR
Blue IAVI program
14The current pipeline is inadequate
Only hypothesis currently tested in pipeline is
cell-mediated immunity
15Political 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
16More resources are being invested but more still
are needed, especially from Europe
Annual average by country relative to national
wealth (2003-2005)
Investment in AIDS vaccine RD
of GDP (x10-3)
Total over 2005 US759 mn
Country
United States
4.0 5.0
(none)
3.0 4.0
Ireland
2.0 3.0
Canada South Africa Netherlands
1.0 2.0
Norway United Kingdom
Denmark Sweden
0.5 1.0
Australia Brazil China Finland France Germany
India Italy Japan Russia Thailand
lt 0.5
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.
17Developing a high-quality medicine is a complex
and expensive road
18The Global HIV Vaccine Enterprise
Funding Agencies
Scientists
Research Agencies
Shared Scientific Plan
NGOs Community groups
Biothech Pharma
International Organizations
19What is IAVIs role?
20IAVIs mission is to ensure the development of
safe, effective, accesible, preventive HIV
vaccines for use throughout the world
21IAVI, publicprivate product development
partnership since 1996
Access uptake
RD
Clinical trials
Production
Health other systems
Political will finance
- 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 RD
- Contribute to sustainable development of health
infrastructure - Involve communities, policy makers, politicians,
media
22IAVIs niche in AIDS vaccine RD
Filling the gap between public sector basic
research and commercial product development
Public Sector
Biotech Pharma
Biotech Venture Capital
Preclinical and Clinical Trials
Basic Research
Applied Research
Large Scale Efficacy
Advanced Devel.
Early Product Devel.
Vaccine Design
Small Animal
NHP
Phase IIa
Phase I
Phase IIb
Phase III
23IAVI RD Resources
- New Technology Assessment
- Product Development Infrastructure
- Network of Partner-Sites in Developing World
- IAVI Human IAVI Immunology Lab
- Vaccine Development Lab
-
-
Neutralizing Antibody Consortium (NAC)
Vector Design Consortium (VEC)
Control of HIV/ SIV-Live Attenuated Consortium
(LAC)
24Vaccine discovery and development
- 11 clinical sites established in 5 countries in
Africa and in India - 17 clinical trials (phase I and II) with 907
volunteers testing 6 vaccine candidates in 11
countries in Africa, Asia, Europe and North
America - 7 clinical studies in Africa to assess
feasibility of human trials, develop expertise at
sites, and solve key immunological questions - 3 scientific consortia to solve key scientific
challenges in the development of new vaccine
concepts - 2 laboratories to support the scientific
consortia and human trials, providing protocols,
training, analytical services, etc - 40 RD partnerships worldwide
25A global RD network, with a particular focus on
developing countries
26Partnership with developing countriesIAVIs
clinical trial network
IAVI India
Pune-NARI, India
Kangemi and KNH-KAVI, Kenya
Chennai-TRC, India
Entebbe-MRC, Uganda
IAVI East Africa
Masaka-MRC, Uganda
Kilifi-CGMRC, Kenya
Kigali-PSF, Rwanda
Lusaka-ZERHP, Zambia
Medunsa, South Africa
Cape Town-DTHC, South Africa
IAVI Southern Africa
Soweto, South Africa
27Product Development Prioritization of Candidates
Percent Positive Responders
Geometric Mean SFC/milion and Range of Responses
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.
28 IAVI Clinical Research StudiesPrepare for
Efficacy Trials Inform Vaccine Design
P Fast, M Price, N Ketter, J Gilmour, etal
29The IAVI model working with developing countries
- An innovative approach to RD of an AIDS vaccine
for nations that most need it - Ensuring that vaccines will be available,
accessible and used - Using a development approach
- Create an enabling environment for research
- Promoting national ownership and sustainable
in-country commitment - Addressing the social and political context
related to research in different cultural
settings - Building support and participation in research
- Bring the voices of developing countries to the
global call for investment in AIDS vaccine
research - Mobilizing countries as integral to the process
- Supporting strong and well-informed developing
country voices
30The IAVI model working with developing countries
- Use a development approach to RD
- 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 RD within the context of
sustainable development and social responsibility
31An example(1) Site development
Uganda Virus Research Institute BEFORE Site of
Proposed UVRI-IAVI Lab Clinic
32UVRI-IAVI Lab Clinic in Entebbe, Uganda AFTER
- Lab/Clinic built
- LaboratoryValidated 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
33An example(2) Training and education
- Vaccine Literacy
- Education programmes for
- Healthcare workers
- Counselors
- Community Advisory Board
- Community Workers
34An 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/pre-adolescents 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 PATHs HPV Vaccine
Evidence for Impact project
35PATH and IAVI strategic partnershipIntroducing
HPV vaccines in the developing worldbridging
reproductive health with the global response to
aids
- Objectives
- Country Introduction
- Implementing Research
- Testing Key aspects
- Strengthening Decision-making
- Policy Analysis
- Market, supply and demand analysis
- Develop decision-making tools
- Global Advocacy
- Coalition building
- Incorporating HPV vaccine in development agenda
- South-South cooperation
- Shared challenges for
- HPV and AIDS vaccines
- Targeting Adolescents
- Sexuality and Stigma
- Delivery Strategies
- Complex Messages
- Stakeholder Support
- Demand and Financing
- Rapid Introduction
- Women and Reproductive Health
36While important progress is being made, equally
important challenges remain
Issue
What it means
- HIV hyper-variability
- Immune correlates of protection are still unknown
- Relevant animal models lacking
- Clinical trials long and costly
- We are tackling a moving target
- Need to test in people
- Success will take time
Scientific
- Long term effort requires long term, high level
global commitment - leading to action - Market incentives for industry activity lacking
- Ethical, regulatory, IP issues
- Health systems challenges
- Until recently not a priority we need sustained
political support - Build private sector engagement
- Optimize environment for safe, ethical trials
Policy Political
37IAVIs Innovation Fund
- Your ideas
- Breakthrough technologies
- 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
- Our offer
- Seed funding
- 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 RD
- 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
38IAVIs public policy research activities
- Activity
- The business case
- Modeling the impact of AIDS vaccines
- Analyzing the potential demand for AIDS vaccines
- Supporting RD
- 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 RD 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
39The road to a vaccine is long but there are
many achievements on the way, in the South
Healthcare workers who received training
National policies for HIV vaccine research
11 clinical labs sites in Africa and India
- Medical Ethical committees
- Standards of Care for volunteers
- Education for communities and journalists
- Voices from the south in the global arena
- And many others
27000 people who received VCT
Community and gender advisory boards
40And in the North
Global HIV Vaccine Enterprise
3 scientific consortia with scientists from
across the world
Innovation Fund
Financial commitment
Resource tracking
Political commitment
41We need your support
- To ensure that political commitment to AIDS
vaccine RD is sustained for as long as needed - To build an supportive environment with the right
policies - To raise sufficient financial support for AIDS
vaccine RD 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
42A variety of incentives can stimulate development
and delivery by industry
PUSH Mechanisms reduce costs
PULL Mechanisms increase revenue
- Transferable IP rights
- Purchase Funds
- Advance Market Commitments
- Tax credits on sales
- Patent buyouts
- PDPPP support
- Fund for innovation
- Continued research subsidies/tax credits
- Fast-track review
- Milestone payments for RD breakthroughs
- Health systems development
43IAVIs policy research policies need to be
improved and an integrated approach is essential
In order to make available the resources
required to develop an effective AIDS vaccine an
enabling political environment and the correct
policy choices must be made
44IAVIs partners in Europe
Industry - Berna, Switserland - Crucell,
Netherlands - Cobra, UK - GSK Biologicals,
Belgium - Bioption, Sweden - FIT Biotech,
Finland - IDT, Germany - Transgene, France
AIDS organisations - AIDES, France - AIDS Fondet,
Denmark - Aidsfonds, Netherlands - Deutsche AIDS
Stiftung, Germany - El Grupo De Trabajo Sobre
Tratamientos Del VIH (gTt), Spain - Finnish
AIDS Council, Finland - HivNorge, Norway -
National AIDS Trust, UK - Noahs Ark, Sweden -
SENSOA, Belgium
Vaccine development
- Academia
- - Centre dImmunologie de Marseille-Luminy,
France - Imperial College, London, UK
- Karolinska Institute, Sweden
- Medical Research Council, Oxford, UK
- St. Georges University of London, UK
- University of Amsterdam, The Netherlands
- University of Oxford, London, UK
Advocacy mobilization
20
45IAVI gratefully acknowledges the support of our
donors