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GENE THERAPY ADVISORY COMMITTEE Health Departments of the United Kingdom 2000 22501868850 GENE THERAPY ADVISORY COMMITTEE SIXTH ANNUAL REPORT January 1999 — December 1999 Health Departments of the United Kingdom 2000 The GTAC Secretariat may be contacted at: Department of Health 652C Skipton House 80 London Road LONDON SEI 6LH Tel: 020-7972 1518 Fax: 020-7972 1717 EMail: [email protected] Gene Therapy Advisory Committee - Sixth Annual Report FOREWORD The first gene therapy clinical trial to be approved this opportunity to thank the NETS subgroup of started in September 1990. Since then, more than GTAC for their input into updating the guidance 400 clinical protocols have been approved worldwide. notes for investigators and reviewing the new More than 10% of these have taken place in the UK, developments. accounting for around 50% of all European studies. Applications to GTAC this year have focussed on gene GTAC also owes enormous gratitude to the external therapy approaches to develop potential treatments experts who review proposals to conduct gene for cancer. therapy research and to the expert advisors with whom the Committee consult. | would like to take As we reach the end of this first decade of gene this opportunity to thank all our external advisors for therapy research, | am pleased to note encouraging their efforts over the reporting year. evidence of positive clinical results has emerged from trials for severe combined immune deficiency (SCID- Finally, it gives me immense pleasure to welcome Dr IX) and for haemophilia. As well as for its successes, Sohaila Rastan, Ms Caroline Benjamin and Mr Michael the past year will also be remembered as that in Harrisonw,ho joined GTAC in December 1999. which the first gene therapy treatment-related death occurred in the USA. In September 1999 an |8-year- old man died as a consequence of participating in a phase | gene therapy trial using an adenovirus vector to correct an ornithine transcarbamylase deficiency (OTC), serving to highlight the importance of effective and efficient monitoring of patients involved in gene therapy trials. In the spring of 1999 GTAC had already commenced a review of serious adverse events and issues related to the monitoring of patients involved in gene therapy research.As a consequence of information received in relation to the USA OTC study, the GTAC review focussed on the adenoviral gene therapy trials. Professor Norman C Nevin Although no major life-threatening toxicity had 2000 occurred with the use of adenoviral vectors, it was decided to convene a working group to develop recommendations for patient monitoring in adenoviral gene therapy studies. GTAC has been concerned about the lack of provision for long-term follow-up of patients who have received gene therapy. This year, with the co- operation of clinical investigators, GTAC have established a confidential mechanism which will operate via the National Health Service Central Register and provide for the long-term follow-up of UK participants in gene therapy research. Gene therapy clinical trials must continue to be conducted to the highest scientific and ethical standards with patient welfare and safety being paramount. GTAC’s first guidance notes were published in 1994 and | welcome the publication of GTAC’s updated guidance to proposers. |w ish to take aaa ye 7 -_ mo yore: toe 1d oa? PO) setbrseged ata gian a= EO satan Zines ho in FGI rit? WHS are rion a ee Is vis 305 : ,- re ny @ a wif atl sD ee a ae 2 tw vee oon! rerio) arws eeeene ay PATS?” a eeegiviem. ieseat5 to wigs co & Aw aos ialyevgiltrens st Gene Therapy Advisory Committee - Sixth Annual Report CONTENTS PAGE Part | GTAC Sixth Annual Report SE CCIOII NN ME COLO COS CADE OV OUR MI 9D oree eaeG a Seare xerp tesoee scdncacsa ndc nsa,denannnctadeecetne nsaveracesedeoses 3 e@ Phase | trial of immunotherapy with adenovirus-interferon-y in malignant melanoma.............++ 3 @ Gene directed enzyme pro-drug therapy for the treatment of head and neck cancer... 4 e@ Gene directed enzyme pro-drug therapy for the treatment of liver CANCE? .......eeeeesseseeeeeeeeeeeeeees 4 e A phase Il trial of preoperative intratumoural injection with Onyx-015 in patients with resectable squamous cell tumours of the head and neck.............ssscssscsssscsssscessecssecessseescsecseeeees 4 e A study of the potential efficacy of modified Herpes simplex virus following IneracuMOULral INjECtion MtO Primary Malignant SOMA ...4.......:..<<0c<ccsenceosscenasaraeoreoeensnssossnsescorsensnsnenondes 4 e@ A phase II/IIl trial of chemotherapy alone versus chemotherapy plus SCH58500 in newly diagnosed stage III ovarian Cancer patients ...............s.cecccsscssecesessesesecossesesecsesececsssecesscseseseeresees 5 Section 2. Protocols still under review at the end of December 1999. e@ Gene therapy protocol for the use of MetXia-P450 for the treatment of ovarian cancet........... 6 e@ Angiogenic gene therapy for peripheral arterial occlusive disease.............ssesssscsssssssessssessesesseeseseeees 6 Séction 3.5 Amendment CO Previously approved PPOtOCOls <oc.5..cesstse csecseccnsceens cccrscnsontoneessese nebesuecséuncbscesuasecnshenncnscte 1 SE CCIONN A MMLC OUI AE ON VuI SSEICS eg te heaton cetacean fee on coach cue one nace marae tne easecesteeb as Sesbaswcsnc natn outatpauertncaacdosayencvee 8 Section 5. The GTAC New & Emerging Technologies Subgroup (NETS). ............cssssessssscecessssccesssseeeseesseeeeeses 10 SECU MI Ome ROLCLT C OS sorcerer Nas usa en ercene Pot copes ea on te celcnat bacas neceocen nce dhecebsncennedbsnisnssachernetines 2 SGCEIOTI gem SS 2 yr cee eects eran ene enns gee cece ae tee sesteacteredetpcanns TooaSes eons se oeMAos ae aeaneiewiovonesoebis 13 PART 2 GTAC Guidance Documents SECCION Le mC LAN SUCROSSEOS C ES parece creer ste acca see tees scien conan eatonsea ca sbeheeveon teas spico nh pent sn vassnibeksasassebvesuiens 17 SECtiON? Z-qm RCDOFE, OF UG AAGEMOVINUS. VVOFKITIS PAINY acc casctexsapscucsscopnutereststesvtes-ontewsantesccovsnccoenesascelen-anctocdsurcsnsdossons 30 ANNEXES | OL COCML IVIS TO PRETO LOIRE eter teeter tig cece acer ss ceca een ye canee cs ad lcs gmsny prs comsta sadovocrestyvansenjansecewonriensnnensnabiins 34 2 Ieriaber state: Ob. 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