AIDS VaccinesAdvancing Development through Innovation
Frans van den BoomVice President IAVI European Programmes
24 October 2007
Helsinki, Finland
Understanding global inequalities
Private health spending Malaria cases
Dorling D (2007) Worldmapper: The Human Anatomy of a Small Planet. PLoS Medicine 4(1)13-18
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Global, neglected and most neglected diseases (WHO & MSF)
3
World pharmaceutical market(>$600 bn in 2005)
Most neglected diseases(e.g. dengue, Chagas)
Neglected diseases(e.g. AIDS, malaria,
tuberculosis)Global diseases
(e.g. measles, diabetes)
R&D for neglected diseases: PPPs are changing the field
Source: Moran (2005) A breakthrough in R&D for Neglected Diseases: New Ways to Get the Drugs We Need. PLoS Medicine 2(9):e302.
• 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 neglected-disease divisions since 2000
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
Why do we need New Prevention Technologies?
Our tools today are not enough to stop AIDS
Source: UNAIDS 2006Photos: WHO/UNAIDS
New adult HIV infections in low- and middle-income countries
Total new infections averted by an AIDS
vaccine between 2015-2030
30% efficacy, 20% coverage 5.5 million
17 million50% efficacy, 30% coverage
70% efficacy, 40% coverage 28 million
0
1
2
3
4
5
2000 2005 2010 2015 2020 2025 2030
New
Infe
ctio
ns (M
illon
s)
Vaccine introduction
Base
Low scenario
Medium scenario
High scenario
A vaccine could save millions of lives
IAVI impact forecasting; Policy Brief #10, November 2006
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
Around the world, 23 countries are conducting AIDS vaccine trials (around 30 vaccine candidates in development)
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
AIDS 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
Vaccinia (Cocktail) St. Jude’s
Viral Vectors- Other
VEE (Clade C) AlphaVax [formerly IAVI]
AAV-2 (Clade C) IAVI-TGEN
NIAID/CHAVIChimeric Adeno Vectors
BCG
VSV
CAVD BMGFAdeno: Chimeric and Ad-11
Pox: NYVAC, MVA
Low sero-prevalent AAV
Reovirus
Newcastle Disease
HIV/VEE Chimeras
HIV/VSV Chimeras
BCG
IAVI Vector ProgramSendai
CMV
Simian Adeno (GSK)
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
Blue = IAVI program
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
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.
Total over 2005 = US$759 mn % of GDP (x10-3)
Country
4.0 – 5.0
2.0 – 3.0
1.0 – 2.0
0.5 – 1.0
< 0.5
Ireland
United States
CanadaSouth AfricaNetherlands
NorwayUnited
KingdomAustralia
BrazilChina
FinlandFrance
Germany
IndiaItaly
JapanRussia
Thailand
3.0 – 4.0 (none)
DenmarkSweden
Annual average by country relative to national wealth (2003-2005)
More resources are being invested …but more still are needed, especially from Europe
Investment in AIDS vaccine R&D
DiscoveryDiscovery
Exploratory DevelopmentExploratory Development
Full Full DevelopmentDevelopment
RegistrationRegistration
Large Amounts ofCandidate Medicine
Synthesized
Project Teamand Plans Synthesis
of Compounds
EarlySafety
Studies
CandidateFormulations
Developed
ExtensiveSafety
Studies
Screening
Studies in HealthyVolunteers Phase I
Candidate Medicine Tested in3-10,000 Patients (Phase III)
Studies in 100-300Patients (Phase II)
Clinical DataAnalysis
$$$
$$
$
$$$$
Developing a high-quality medicine is a complex and expensive road
IAVI’s mission is to ensure IAVI’s mission is to ensure the development of safe, effective, the development of safe, effective,
accesible, preventive HIV vaccines for accesible, preventive HIV vaccines for use throughout the worlduse throughout the world
IAVI, public–private product development partnership since 1996
Research and developmentFill the gap between between public sector basic research and commercial product developmentDevelop vaccine candidates, prioritize the most promising ones and move them into clinical trials
Policy and advocacyEnsure political and financial commitmentCreate a supportive environment for researchPrepare for global access
Engage developing countriesBuilding capacity for R&DContribute to sustainable development of health infrastructureInvolve communities, policy makers, politicians, media
Political will & finance
R&D Clinical trials
Production Health & other systems
Access & uptake
IAVI’s niche in AIDS vaccine R&D
Preclinical and Clinical Trials
Small Animal
BasicResearch
Applied Research
Large Scale Efficacy
Advanced Devel.
Early Product
Devel.
Vaccine Design
NHP Phase IIaPhase I Phase IIb Phase III
Public SectorBiotechPharma
Biotech Venture Capital
Filling the gap between public sector basic research and commercial product development
IAVI R&D Resources
•New Technology Assessment
•Product Development Infrastructure
• Network of Partner-Sites in Developing World
•IAVI Human IAVI Immunology Lab
•Vaccine Development Lab
•
•
NeutralizingNeutralizingAntibodyAntibodyConsortiumConsortium(NAC)(NAC)
Vector DesignVector DesignConsortiumConsortium(VEC)(VEC)
Control of HIV/Control of HIV/SIV-Live AttenuatedSIV-Live AttenuatedConsortium (LAC)Consortium (LAC)
Kilifi-CGMRC, Kenya
Entebbe-MRC, UgandaChennai-TRC, India
Medunsa, South Africa
Soweto, South Africa
IAVI East Africa
IAVI Southern Africa
Kangemi and KNH-KAVI, Kenya
Masaka-MRC, Uganda
Kigali-PSF, Rwanda
Lusaka-ZERHP, Zambia
Cape Town-DTHC, South Africa
Pune-NARI, India
IAVI India
Partnership with developing countriesIAVI’s clinical trial network
Product Development: Prioritization of Candidates
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.
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
6% 17% 49% 20% 5% 62% 92% 46%
35 69 109 130 57 130 80 101
31-40 66-73 44-598 54-385 41-79 55-275 39-193 52-297
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
Protocol Summary Status
A HIV prevalence Completed: n=6500
B HIV incidence 4800 enrolled
CHIV early infection & HIV control study
> 150 enrolled
D Laboratory reference rangesCompleted: 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
IAVI Clinical Research Studies:Prepare for Efficacy Trials & Inform Vaccine Design
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
Vaccine Literacy
Education programmes for:
Healthcare workersCounselorsCommunity Advisory BoardCommunity Workers
An example:(2) Training and education
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/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 PATH’s “HPV Vaccine: Evidence for Impact” project
PATH and IAVI strategic partnershipIntroducing HPV vaccines in the developing world:
bridging 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
While important progress is being made, equally important challenges remain
HIV hyper-variability
Immune correlates of protection are still unknown
Relevant animal models lacking
Clinical trials long and costly
Scientific
We are tackling a moving target
Need to test in people
Success will take time
Issue What it means
Policy &Political
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
IAVI’s Innovation Fund
Your ideas
Breakthrough technologiesNovel immunogens e.g. bNAb, host targetsTarget novel immune mechanisms e.g. innate immunityNew delivery modalities e.g. replicating vectors, mucosal deliveryNew ways to address key challenges – e.g. from systems or computational biology
Technologies that optimize existing candidates
Adjuvants and formulationAntigen optimization Delivery technologiesPrime-boost combinations
“Enabling technologies”High throughput screening methodologiesHigh throughput immunogen design
Our offer
Seed fundingNon 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&DAccelerated regulatory pathwaysLower risk of investment in early phase technologies
Opportunity for longer-term collaborationFunding & partnership over the long haulIAVI experience (and infrastructure) with regulatory approval and clinical trials including in developing countries
IAVI’s public policy research activities
ActivityThe ”business case”Modeling the impact of AIDS vaccinesAnalyzing the potential demand for AIDS
vaccines
Supporting R&DRegulatory and ethical approval for AIDS
vaccine trialsAn advance market commitment (AMC)
for AIDS vaccinesCollateral benefits of vaccine trials
The wider contextAIDS 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
Medical Ethical committees Standards of Care for
volunteers Education for communities
and journalists Voices from the south in the
global arenaAnd many others …
11 clinical labs & sites in Africa and India
Healthcare workers who received training
27000 people who received VCT
National policies for HIV vaccine research
Community and gender advisory boards
And in the North
Global HIV Vaccine Enterprise
Financial commitment
3 scientific consortia with scientists from across the world
Innovation Fund
Resource tracking Political 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
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
- Noah’s Ark, Sweden
- SENSOA, Belgium
Academia
- Centre d’Immunologie 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
Industry
- Berna, Switserland
- Crucell, Netherlands
- Cobra, UK
- GSK Biologicals, Belgium
- Bioption, Sweden
- FIT Biotech, Finland
- IDT, Germany
- Transgene, France
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Vaccine development
Advocacy & mobilization