GenStar Reports Successful Repeated Administration of MAX-AD FACTOR VIII in Pre-Clinical Models at American Society for Hematology Meeting
ORLANDO, Fla.--(BW HealthWire)--Dec. 10, 2001--GenStar Therapeutics (Amex: GNT - news)--
Update Provided on Expression of Factor VIII in First Treated Patient
GenStar Therapeutics (Amex: GNT - news) today announced pre-clinical and clinical data from the Company's ongoing gene therapy studies to treat hemophilia A. In this disease, a defect in the Factor VIII gene results in a decrease in the production of the Factor VIII protein essential for blood clotting. In both a pre-clinical and clinical setting, Genstar's researchers have administered the Company's MAX-AD FACTOR VIII gene therapy product, a gene delivery system derived from a common cold virus, in order to increase expression of circulating Factor VIII and correct the bleeding abnormality.
According to a presentation at the 48th Annual Meeting and Exposition of the American Society for Hematology, one patient treated with MAX-AD FACTOR VIII gene therapy demonstrated expression of Factor VIII (approximately 1%) that was sustained for 4 months despite the presence of neutralizing antibodies against adenoviruses (titer 1:4,000). This finding was further supported by pre-clinical results in animal models showing that MAX-AD Factor VIII treatment for hemophilia A led to increased and sustained therapeutic levels of Factor VIII protein despite the presence of neutralizing anti-adenoviral antibodies. In the animal studies, administration of MAX-AD Factor VIII in conjunction with immunomodulators permitted successful repeated administration and was associated with lower total and neutralizing anti-vector antibody responses.
Robert E. Sobol, M.D., Chief Executive Officer of GenStar, stated, ``We are pleased to observe sustained expression of Factor VIII in our first patient and to demonstrate successful repeated therapy in pre-clinical studies. Being able to re-administer therapy is key in chronic diseases, such as hemophilia, where patients may need to receive therapy throughout their lives''.
GenStar's clinical study is open for accrual and will be evaluating additional patients. Transient liver and hematologic laboratory abnormalities observed in the first patient have returned to normal values and the trial has resumed at a lower dose with a dose escalation design.
GenStar's pre-clinical study was designed to determine if the antibody response against MAX-AD Factor VIII upon re-administration could be inhibited by transient immune suppression. In the study, mice were pre-treated with immune modulating factors (anti-CD4, anti-CD40 ligand (CD40L), or anti-CD19) or a control, and then received MAX-AD Factor VIII. With each of these modulators targeted against different components of the immune system, a decrease in antibodies against the vector were observed compared to the controls where they were not administered and resulted in therapeutic levels of Factor VIII.
Hemophilia A is a potentially life threatening hereditary disease that affects over 50,000 people in the United States and Europe. The disease results from a defect in the Factor VIII gene, which produces the Factor VIII protein essential for blood clotting. Current therapies for Hemophilia A are based upon intermittent injections of the Factor VIII protein that do not provide the sustained levels of Factor VIII needed to prevent bleeding episodes characteristic of the disorder. GenStar's product carries the entire human Factor VIII gene sequence and uses a molecular switch with a genetic sequence designed for increasing Factor VIII expression in the liver, one of its normal biological sites of production.
GenStar's MAX-AD FACTOR VIII gene therapy product for Hemophilia A is a gene delivery system derived from a cold virus. In contrast to earlier gene delivery approaches, GenStar's product has been engineered to remove all the viral genes, providing a large DNA-delivery capacity for therapeutic genes that are responsible for the production of Factor VIII. MAX-AD has a larger gene delivery capacity compared to earlier generation vectors.
GenStar Therapeutics is a biotechnology company currently developing gene therapy products for the treatment of hemophilia A, prostate cancer, and HIV/AIDS. The company's lead product for the treatment of hemophilia is being developed in collaboration with Baxter International and its hemophilia, prostate cancer and HIV/AIDS product development programs are supported, in part, by grants from the National Cancer Institute and the National Institutes of Health. MAX-AD, the company's core technology is a gutted adenoviral vector that can be applied broadly across gene-based applications. For more information, please visit the company's website at genstar-rx.com. |
