BioWorld International Correspondent
LONDON - The gene therapy company Ark Therapeutics Ltd. said EG009, a combination of a gene and a prodrug, doubled patient survival time in a Phase I/IIa trial in patients with malignant glioma.
Alan Boyd, director of development, told BioWorld International, "This is really encouraging, and is showing everyone we have developed the capacity of turning genes into medicines."
A larger Phase IIb trial, which will recruit 60 patients, is already under way in Finland, with results expected around the end of 2001. "We will wait for the data before deciding if we should apply for approval after this trial," Boyd said. "As the other treatments for glioma are not much good, we could get approval at this stage."
EG009 consists of a herpes simplex vector carrying a gene for the enzyme thymidine kinase that is injected into the brain following surgical removal of the glioma. Cells transfected with the gene produce thymidine kinase, which converts intravenously administered ganciclovir into a toxic nucleotide analogue. This blocks DNA replication and kills the cells if they try to divide. The nucleotide also migrates to and kills surrounding, but nontransfected, brain cells. Healthy neurons rarely divide, and thus are not affected.
The controlled, open-label study was carried out in 21 patients at the Department of Neurosurgery at the University of Kuopio in Finland. The mean survival time for the EG009 patients was 15 months, compared with 8.3 months for the controls. The treatment was well tolerated.
Ark Therapeutics, based in London, has now completed nine clinical trials of gene therapeutics. In November the company was granted orphan drug status by the FDA for Trinam (EG004) for the prevention of intimal hyperplasia (the overgrowth of smooth muscle cells) in certain vascular anastomoses. Boyd said a U.S. Phase II/III trial will begin later this year. Trinam uses a biodegradable collar/reservoir delivery device fitted at the time of surgery to deliver a vascular endothelial growth factor (VEGF) gene using a lipid vector.
Delivery in this way is aimed at enhancing local gene delivery while limiting systemic exposure. The lipid vector is produced by Valentis Inc., of Burlingame, Calif. Hyperplasia is a frequent complication after vascular surgery, resulting in the blockage of the vessels in up to 60 percent of patients. It is triggered by the surgery and insult to the vessels. The VEGF protein increases the production of nitric oxide in the endothelium, which, in turn, is responsible for inhibiting smooth muscle cell proliferation.