Haemophilia gene therapy trial stopped

A US biotechnology firm announced last week that it is discontinuing its haemophilia trial, citing technical and safety reasons. Avigen said that it was stopping the trial so it could concentrate on neurological diseases, but it also said that the gene therapy treatment for haemophilia faced 'certain scientific, regulatory and clinical hurdles'.

The company is trying to develop new treatments for haemophilia B, a blood clotting disorder caused by the lack of a crucial protein called Factor IX. Avigen aimed to replace this missing protein by using a virus to deliver the Factor IX gene into a liver artery. The treatment has already proved successful in dogs affected by the disorder. However, Avigen halted the human trial after two of the seven patients developed mild side effects. Both participants had slightly raised levels of liver enzymes, which suggests that the virus used, an adeno-associated virus (AAV), triggered an immune response in the body.

Study leaders Mark Kay and Katherine High hope that they can modify the trial, and carry on testing the therapy. 'In terms of the science, I think things are going pretty well', High told the journal Science. Kay says the first step is to confirm that the AAV gene delivery system did trigger the immune response, and then perhaps to start another trial, in which patients are treated briefly with immunosuppressive drugs at the same time as the gene therapy treatment.

Gene therapy researchers say that Avigen's decision to stop the trial isn't a major setback to the field, because the safety problem was minor, and seems to be specific to the haemophilia trial. Some other trials are also using AAVs to deliver genes, but most are injecting small doses into particular tissues, rather than arteries. This approach is less likely to trigger side effects, says US gene therapy expert Savio Woo.

The US National Haemophilia Foundation (NHF) remains optimistic about the potential for gene transfer for haemophilia, and says it will continue to fund such research. 'This is a time to redouble our efforts to support promising research so that breakthroughs for haemophilia and all genetic diseases will happen sooner rather than later', said NHF president Richard Metz.