After the second occurrence of a leukaemia type illness in a patient in a gene therapy trial in France for X linked severe combined immune deficiency disorder (SCID), the US Food and Drug Administration has halted all trials that use retroviral vectors for inserting genes into bone marrow stem cells.
The move is described as a “precautionary measure” pending investigation. No evidence has been shown of leukaemia in any of the patients in the United States who have had this type of gene transfer, says the FDA.
Last September the French investigators, Dr Alain Fischer and Dr Marina Cavazzanna- Calvo at the Necker Hospital in Paris, reported that one of 11 patients with X linked SCID they were treating had developed T cell leukaemia about three years after receiving the gene transfer.
At that time the FDA suspended the three gene therapy trials of SCID patients in the United States that most closely resembled the French trial and stopped patient enrolment. The UK Department of Health's Gene Therapy Advisory Committee also recommended that additional measures be put in place to protect patients undergoing gene therapy trials (12 October, p 791).
The FDA's latest step puts on hold an additional estimated 27 trials that use retroviral vectors to insert the defective gene into haematopoietic stem cells.
The latest development is disappointing, as the early results of the French trial were so promising. Seven of the patients are in good health, with their immune system restored. One patient was regarded as too ill at the time of the procedure to benefit.
The development is regarded more as a temporary setback than the end of the road for gene therapy. Dr Philip Noguchi, acting director of the FDA office that regulates US gene therapy studies, says he regards gene therapy as a promising treatment for patients who have not benefited from current treatments, such as bone marrow transplantation.
An FDA scientific advisory committee will hold a meeting late in February. Noguchi said the committee will be given the known data and asked to make recommendations.
Supporting the FDA's action, the American Society of Gene Therapy says that a key question is why this has occurred only in trials involving patients with SCID and not in the other clinical trials that use retroviral vectors targeted at haematopoietic stem cells.
The society is conducting its own investigation and will report its findings at its annual meeting in June. It is possible, says the society, that the gene that encodes a T cell growth factor triggers the risk of leukaemia. Other possibilities are the fact that the patients are all infants, the nature of SCID itself, and the gene transfer technique.