SAAVI VTN

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Connecting the Chain SAAVIs Vaccine R D
ProgrammePeter T. Manyike, Ph.D.Scientific
and Clinical Affairs Advisor
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Brief History

• Established in 1999 by the national South African
  government and Eskom
• Lead programme of the Medical Research Council of
  South Africa (MRC) based in Parow, Cape Town
• Primary funding
• Department of Health
• Department of Science and Technology
• Eskom
• Additional Funding
• Transnet, Implats, EU

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SAAVIs Mandate

• SAAVI is tasked with developing an affordable,
  effective and locally relevant preventative (and
  therapeutic) HIV vaccine for southern Africa

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SAAVIs Main Activities

• Laboratory Sciences
• Vaccine design, construction and characterisation
• Animal safety and immunology studies
• Non-human primate challenge studies
• GLP-compliant regulatory studies
• Clinical Trials
• Enabling clinical trial environment
• Core clinical trial site financial support
• Community involvement, social science, ethics and
  law
• Community involvement and consultation
• Capacity building
• Others
• Manufacturing
• Bio-Informantics
• Data management
• Actuarial assessments
• Non-human primate centre

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Distribution of SAAVI-affiliated Research Sites
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Directorate staff
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How Vaccines are Developed
Preclinical development Manufacture (GMP)
Basic research
Clinical trials
Phase I/II
Phase III
Phase IV
Laboratory
Human research
in vitro animal studies
Safety, Immunogenicity
Discovery
Exploration
Efficacy
Vaccine concept
Experiments in rodents and primates
Human trials
Safety, immunogenicity
Likelihood of protection in humans
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Clinical trial phases in humans
n of participants

• Phase

Objectives
Safety (Immune reaction)
20-150 / trial
Additional Safety - Immune reactionDose
finding - Administration route Vaccination
schedule
100s / trial
Efficacy (against infection or disease)
1000s/ trial
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SAAVIs Vaccine R D Process
Phase III Efficacy
Characterisation of HIV-1 epidemic
Phase I / II
Vaccine strain selection
MCC/Regulatory
Vaccine Construction And Characterisation
Toxicity Testing
cGMP Production
Potency assay
A-L. Williamson et al.
Pre-clinical Immunogenicity
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Clinical Trials (Jun 2006)

• Phase I
• HVTN 042 (VEE, gag C) (Nov 2003, enrolm compl) -
  Alphavax
• IAVI 001 (MVA, Gag/CTL ep. A) (Nov 2003,
  enrolment compl) - Oxford
• HVTN 050 (Ad5, gag B) (Oct 2004) - Merck
• HVTN 059 (VEE, gag C) (Feb 2005) - Alphavax
• Phase II
• IAVI A002 (AAV) (Nov 2005, ongoing) Targeted
  Gen.
• FIT Biotech (Apr 2006, ongoing) Therapeutic
  Vaccine
• HVTN 204 (DNA / Ad5 ABC) (Q2 2006, to start soon)
  - VRC
• Planned
• SAAVI (Phase I) - DNA / MVA (C) (Q3 2007)
• HVTN 503 (Phase IIB) - (DNA / Ad5 polyvalent
  B) (Aug 2006)

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SA Regulatory Environment

• Medicines Control Council (MCC)
• Formal review and approval meetings every 2
  months (6 times/year)
• MCCs Clinical Trial Committee
• HIV Vaccine Task Group (HVTG)
• Pre-submission meetings
• Review of preclinical data and proposed clinical
  development programme
• Meets every 2 months
• Legally non-binding recommendations

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Manufacturing

• DNA / MVA Manufacturing skills/facilities not
  yet available in the country
• Priority area for local skills development
• Technology transfer
• Clinical lots
• Good Manufacturing Practices (cGMP)
• Commercial lots scale-up
• Regulatory challenges bridging studies?

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Vaccine Manufacturing
SAAVI Directorate
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Strategic alliances

• AAVP
• NIH
• HVTN
• IAVI
• EU
• Others

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Challenges

• Clinical trials - adolescents Regulatory
  framework
• Trial site preparation expansion and new sites
  development
• Funding international collaborators
• Manufacturing local capacity development
• Liability considerations multinational sites
• IP and patents expensive product access
• Clinical trial specimen storage local sample
  analysis

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Conclusions

• Continues to produce as well as ensure testing of
  vaccines
• SAAVI - a national biotech R D asset
• Independent, yet collaborative networking
• Expand to successfully exercise mandate
• Clinical trials
• Local community involvement
• Development of new clinical sites
• Manufacturing
• International bio-manufacturing collaborators
  (USA)
• Long-term local manufacturing capabilities
• Community Involvement
• Strong community links, including at clinical
  trial sites

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Thank you