Note of the 56th GTAC meeting held on 7 December 2005 in London

Present: Professor Norman Nevin (Chair), Professor Terry Hamblin, Professor Alex Markham, Mrs Fiona Sandford (from item 6), Mr Michael Harrison, (to item 10), Professor David Harrison, Mrs Debbie Beirne, Professor Jim Neil, Professor Martin Gore, Dr Caroline Benjamin, Dr Adrian Lepper, Professor Nick Lemoine, Dr Michael Waterhouse, Dr Richard Ashcroft, Professor Andrew Baker and Professor Mary Collins (afternoon only).

Secretariat: Dr Monika Preuss, Dr Jayne Spink, Mr Daniel Gooch and Miss Joanna Edwards

Observers: Dr Paul Logan (HSE) (Item 5+)

Apologies: Dr Peter Harris, Professor Andrew Lever and Bishop Dr Lee Rayfield

1: Welcome

The Chair welcomed the Committee to its 56th meeting.

The Chair thanked Professor James Neil and Dr Caroline Benjamin both of whose terms were due to finish with the committee for their commitment and expertise during their tenure with GTAC. Thanks were also given to Dr Jayne Spink who after a total of 40 meetings was leaving the secretariat.

The Chair then welcomed two new members to the committee: Professor Andrew Baker who is GTAC's new Cardiovascular expert and Professor Mary Collins who has joined as the Virology expert and was present for the afternoon session. A welcome was also given to Joanna Edwards who has recently joined the secretariat.

2: Minutes of the 55th meeting of GTAC

The minutes were agreed as an accurate and true record of the 55th meeting.

3: Matters Arising

A number of letters were sent out and received, concerning correspondence arising from the last meeting, none of which gave rise to any discussion.

4: Report from the GMP gene therapy vector production workshop

There was a small discussion arising from the gene therapy vector production workshop run by the Department of Health.

5: Update on GTAC's role as UKECA recognised MREC

GTAC received REC recognition on 15 November.

6: Update on lentiviral vectors

The members received a presentation on lentiviral vectors which gave rise to limited discussion.

7: A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multi-Center Study of Ad2/Hypoxia Inducible Factor (HIF)-1a/VP16 Administered by Intramuscular Injection to Patients with No or Poor Option Chronic Critical Limb Ischemia

This is a new trial with a product that is well known to GTAC, an adenovirus, which produces the protein hypoxia induced factor-1a.

Patients with peripheral arterial disease and atherosclerosis frequently suffer critical limb ischemia, which develops when the blood flow does not meet the metabolic demands of tissue at rest. This new study proposes to administer hypoxia induced factor-1a (HIF-1a) via an adenoviral vector.

The Committee conditionally approved the new trial.

8: Consultation on future design of retroviral vectors

At the last meeting, there was a brief discussion about a draft open letter from GTAC to gene therapists regarding the recommendation by GTAC/CSM that there should be a move towards the use of self-inactivating (SIN) vectors and non-viral promoters to drive therapeutic genes and others. A letter was sent to UK gene therapists, BSGT, ESGT, ASGT, BIA, FDA and RAC on 26 November for consultation. The responses were given in the meeting papers. The committee concluded that it did not appear that it was the correct time to move towards the use of SIN vectors but that they would like to revisit the issue when more evidence is available on their safety.

9: Chairman's Actions

Six Chairman's letters were sent out since the last meeting which produced little discussion

10: SUSAR Update

There has only been one new SUSAR (#185) received since the last meeting. There was no discussion around this issue.

11: Substantial Amendment to GTAC 084:
A Phase I study of immunotherapy for patients with metastatic melanoma using dendritic cells transfected with a plasmid encoding two melanoma antigens

This concerns an application for approval of a substantial amendment to the GTAC 084 melanoma study. It was a request to extend the current cohort to include an additional 15 patients to 25 in total. The additional patients will be treated in the same way as previous patients.

Approval was given for this substantial amendment.

12: Substantial Amendment to GTAC 079:
An open label pilot study to evaluate the safety and immunogenicity of MVA.HIVA, in HIV-1 seropositive adult subjects receiving HAART

The second application for approval of a substantial amendment was for the GTAC 079 HIV study. This covered:

The addition of an "Extension Phase" to include a third, higher dose of MVA.HIVA to be delivered by intradermal injection to sixteen HIV+ subjects.

The committee also discussed some minor comments on the Patient Information Leaflet. The amendment was approved.

13: Additional agenda item:
Application for amendment to the inclusion criteria of GTAC 073 (gene therapy for ADA-SCID)

GOSH came forward with an application to amend the inclusion criteria for patients into the ADA-SCID trial.

GOSH argued that there are a number of recent papers which suggest that maintaining patients on long-term PEG-ADA may result in prolonged immunodeficiency and increased susceptibility to infection.

They proposed that children without a matched donor should be treated by gene therapy without starting PEG-ADA (if clinical condition is stable) or be stabilised on PEG-ADA and then treated by gene therapy regardless of the extent of immune recovery.

The committee declined this amendment at this current time. GOSH were invited to come forwards with further clarification.

Item 14 - Gene therapy for CGD
Update and new application for enrolment (GTAC 046)

The German CGD trial

At the recent European Society for Gene Therapy Conference, Professor Manuel Grez presented new data on the German/Swiss trial for CGD which uses the same vector as the UK study. Data on two patients was presented.

Professor Grez attended the meeting to inform the committee on the following item and to provide an update on the German CGD trial.

New application to enrol CGD patient

This item produced little discussion as the general agreement was that the patient in question could benefit greatly from the procedure and there were no other options for the patient at this time. The application was approved.

Item 15 - Any other business

Members were provided with information on the new EU regulations on advanced therapy medical products which cover gene therapy, somatic (stem) cell therapy (including animal cells), and tissue engineering.

NEXT MEETING - 15 February

GTAC Secretariat
December 2005

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