Summary of Gene Therapy ICH Workshop September 9,2002

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Summary of Gene Therapy ICH Workshop- September
9,2002

• Stephanie Simek
• Branch Chief, Gene Therapy Branch
• Division of Cellular and Gene Therapies
• Office of Cellular, Tissues and Gene Therapies
• CBER/FDA

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Introduction/Background

• Brussels SC meeting (2/02)
• Update on organization of workshop
• SC members provide comments and speakers
• Tokyo SC meeting (5/02)
• Satellite meeting on biotechnology and gene
  therapy
• 3 regions currently harmonized on scientific
  principles

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Introduction/Background-cont.

• Tokyo SC meeting
• Mechanism to exchange scientific expertise and
  experience to foster harmonization
• Three critical point identified as priority areas
  for exchange
• Reference materials standardization for dosing
• Virus shedding
• Germ-line integration

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ICH Workshop on Gene Therapy- Washington DC,
September 2002

• 1st open scientific meeting on gene therapy
• Discussion on utility of using adenoviral
  reference material (ARM)
• Discuss adenoviral shedding issues
• Safety issues regarding the use of Lentiviral
  vectors

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Adenoviral Reference Material

• 1999 Death of a subject enrolled in Adenovirus
  gene therapy clinical trails
• Collaborative effort between industry/academia
  /FDA manufactured wt adenovirus type 5
• Concern over precision and accuracy of adenoviral
  titers
• Provide safety information regarding dose-related
  toxicity
• Safety in regards to amount of replication
  competent adenovirus

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Importance of Reference Material

• Production of more consistent, safer, quality
  adenoviral vectors
• Allow comparability between preclinical studies
• Allow comparability between clinical studies
• Development of regulatory policy

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Adenoviral Vector Shedding

• Addressed intrinsic safety properties of the
  products
• Safe handling in relation to the environment and
  human population
• ICH experts encouraged collection of data
• Decided no specific safety issue at this time
  identified

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Novel Vector Systems Lentiviral Vectors

• Safety issues
• Generation of replication competent virus (RCL)
  during manufacture
• Insertional mutagenesis
• Potential for germ line transmission
• Mobilization of integrated Lentiviral vector and
  recombination with wt-HIV

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Novel Vector Systems Lentiviral Vectors- cont.

• Discussion on importance of developing
  appropriate controls for RCL assays
• Discussion on vector design
• Developing appropriate in vivo animal models to
  study mobilization, potential risk of insertional
  mutagenesis

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Conclusions

• ICH discussion group agreed that investigators
  should use ARM to measure virus particles and
  infectious titer
• Review of accrued data used to correlate safety
  information
• Dose related toxicity
• Level of RCA

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Conclusions cont.

• Recommended collection of adenovirus shedding
  data - revisit topic at a later date
• Recommended tests for RCL be developed
• Recommended development of appropriate in vivo
  animal models for lentiviral vectors
• Agreed Lentiviral vectors could be used in
  clinical applications based on risk/benefit
  considerations.
• Agreed to further discussion at 6th ICH meeting
  in Japan