New Vaccines Working Group

1
New Vaccines Working Group

• Uli Fruth
• Paris 18 October 2005

2

• Global Plan 2000-05
• Global Plan 2006-15
• cost estimates
• impact
• Working Group methods

3
What do we hope to achieve
140
120
100
status quo
80
Incidence rate/100K/yr
ADV birth
60
40
DOTS 70/80
20
AIV mass
ADV mass
0
adapted from C. Dye, Int J TB Lung Dis, 2001
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Global Plan 2000-05
OBJECTIVES
Five candidates in Phase I trials by 2005
M72f protein in adjuvant Reed,
Corixa/GSK USA/Europe MVA-85A Mtb gene
in vaccinia Hill, Oxford UK/Gambia rBCG30
recombinant BCG Horwitz, UCLA USA
Ag85B/ESAT-6 protein in adjuvant Andersen,
SSI Europe
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Global Plan 2000-05
OBJECTIVES
Five candidates in Phase I trials by 2005
rBCGDUreCHly recombinant BCG Kaufmann,
Berlin Q2 2006 Adeno-Ag85AB/Y Mtb genes in
virus Aeras/Crucell Q2/3 2006
at least 1 rec protein, 1 recombinant BCG 3
att Mtb lined up for clinical testing

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The BCG Question

• protects against severe forms of childhood TB
• (and long-lived protection in some
  populations)

• promising results with prime-boost protocols
• in animal models

new vaccine will add something to BCG
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Global Plan 2006-15
OBJECTIVES
Safe, effective, licensed vaccine available
at reasonable cost by 2015

• sufficient production capacity available by
  2015
• widely distributed by 2020

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Vaccine Development Timeline
2015
2015
2011
2012
2013
2014
2005
2006
2007
2008
2009
2010
does it induce the right immune response?
is it safe? HIV, latent TB, children . . .
does it protect against TB?
License, Launch Distribute
Phase I and Phase II trials
Phase III trial
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Pre-Exposure Post-Exposure Vaccination
pre-exposure
primary TB
primary TB

post-exposure
therapeutic?
cure
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BCG - Replace or Repair?
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Parallel track strategy

• Parallel track development - pre- and
  post-exposure idea is to come to a fusion of
  both tracks around 2015

Clinical development 2005 2008
2013
2015
Pre-exposure Post-exposure

• Premature to settle on one implementation
  scenario (modeling)
• Ideal only one new vaccine for pre-
  and post-exposure
• Not ideal but probably acceptable pre
  and post-exposure vaccine different

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Timeline of Milestones in New TB Tool Development
2013-2015 Introduction of improved prophylactic
TB vaccines
2017 Introduction of new drug regimen for TB
2050 Elimination of TB as a public health threat
2000 Stop TB Partnership created
2018 Introduction of first vaccine preventing
transition from latent to active disease
2010 Introduction of first new TB drugs
2000 2005 2010
2015 2020
2030
2040 2050
2007 Introduction of the first improved and new
TB diagnostics
2015 Introduction of diagnostic for latent TB
2010 Introduction of Point of Care TB diagnostic
2000 Amsterdam Ministerial Conference on TB
Sustainable Development
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Vaccine Development Timelines
2015
2015
2011
2012
2013
2014
2005
2006
2007
2008
2009
2010
Site Preparation Epidemiology
Factory Construction Validation, Consistency
End Point Immune Assay Validation
Phase I,II, IIB Protein I Adj 1
Phase III Infants BCGprime/Protein
boost Adolescents - Protein
Ph I,II Protein Ia Adj 2
Preclinical
License, Launch Distribute
Preclinical
Ph I,II Protein 2 Adj 3
Preclinical
Ph I,II rBCG, rTB
Phase III Infants rBCG or rTB prime Viral
Vector Boost Adolescents - Vector
Ph I, II BCG/ viral vector I
Process Develop. Viral l
Ph I, II Viral 2
Preclinical
Preclinical
Ph I, II Protein 34
Phase III Post Infection /- rBCG prime Viral
Vector Boost
License
Preclinic
Ph I,II Viral 3
Preclinic
Ph I,II rBCG 2
Preclinic
Ph I,II Viral 4
Preclinic
Ph I,II Viral 5
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Costs for Vaccine Development
2015
2015
2011
2012
2013
2014
2005
2006
2007
2008
2009
2010
4 trials 40,000 subjects 240
production facility 100
License, Launch Distribute
Phase I and Phase II trials
Phase III trial
million US
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Vaccine Budget for Global Plan
Cost
Gap BCG 1300
0 Research translation
1200 490 Preclinical development
15 15 Site Capacity 15
3 Production/scale-up
192 187 Clinical trials
387
341 Preparation of access 1
0 WG Facilitation
6 5 Total
3116 1041
million US
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Vaccine Impact Post-2015
Vaccine introduction
Pre-exposure
Incidence
Post-exposure (e.g. adolescent vaccination
programme)
Post-exposure in a mass-vaccination paradigm
(everybody!)
Time
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Stakeholders

• Government RD Sponsors (NIH, MRC, EU)
• National Public Health Institutions (CDC)
• Scientists
• Regulatory Agencies
• Philanthropy (BM Gates AERAS, Wellcome Trust)
• Pharmaceutical Industry
• Other Stop TB WGs

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Role of the Working Group
preclinical clinical trials manufacture
Gates, EU, NIH, etc
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Needs challenges

• Preclinical Development
• Need for consensus animal testing protocols
• Lack of models to test specific safety
  aspects, e.g. 'Koch phenomenon'
• Clinical Development
• Need for specific training capacity for TB
  vaccine trials
• Lack of a surrogate marker for
  vaccine-mediated protection against TB
• Normative
• Lack of regulatory guidance specific for TB
  vaccine evaluation/licensure
• Insufficient characterization of BCG
  (strain differences, QC, potency assays)
• Vaccine Introduction
• Lack of impact and cost-effectiveness data to
  guide TB vaccine RD
• Absence of global vaccination strategies to
  target adult adolescent populations

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Working Group Activities

• Prepare Scientific Blueprint
• Elaborate Economic Analysis
• Facilitate International Regulatory
  Harmonization
• Provide Preclinical Clinical Standards
• Ensure timely vaccine production/availability
• Prepare accelerated access in countries