Kaiser's "Death Prompts a Review of Gene Therapy Vector" 2010

A patient receiving experimental gene therapy for arthritis died
- Triggered a review of all trials using the same vector (vehicle used to transfer genetic material into a target cell)
- First fatality in a trial not studying a life-threatening disease (3 patients actually acquired leukemia)
Company doesn’t know what caused the death
- Company not expecting it to be the vector since it has been proven safe for hundreds of patients
- Investigation being carried out by the company and the FDA
- Investigation could take weeks
Gene therapy trial built on the success of Enbrel (protein-based treatment for rheumatoid arthritis that inhibits TNF-alpha (pro-inflammatory cytokine))
- Drug effective but doesn’t always penetrate all joints
- Must be administered regularly
- Adeno-associated virus (AAV) gene used to shuttle the drug directly into the joints
  - Approach safe in rats and primates
- Trial enrolled 127 patients (32 on placebo)
  - 74 received second injection
    - 1 patient died
      - FDA reviewing 28 other trials using AAV
      - One suspect is the gene product
      - Not likely that it’s the AAV vector
        Vector has been used in over 500 patients
        Difference: patients in the RA trial received more than one dose
        Patients could be becoming sensitized to the vector, causing an adverse reaction
Gene therapy has restored health for about 20 SCID patients
- Approach is also showing promise in cancer