Advantagene’s second lead product, GliAtak™ is for treatment of primary brain tumors, a relatively common malignancy for which there is no effective treatment.  There were an estimated 17,000 new cases in the USA and 13,100 deaths from primary nervous system tumors in 2002, the majority of which were malignant gliomas (American Cancer Society, 2002). Slower growing, less aggressive gliomas are referred to as low grade or benign whereas higher grade, malignant gliomas include malignant astrocytomas (36% of gliomas) and glioblastoma multiforme (GBM; 47% of gliomas and 21.7% of all primary brain tumors). Current therapies for this disease, including surgery, radiation and chemotherapy, are essentially palliative.

Many malignant gliomas located within or close to key areas of the brain are not resectable.  Radiation therapy is the major therapy for non-resectable masses as well as for post-resection adjuvant therapy. Its efficacy is limited by the low radiation sensitivity of tumor cells and the inclusion of normal brain tissue within radiation fields.  The median survival time for patients with glioblastoma multiforme is 10 months and the 3-year survival rate is only 6%.  Alternative radiation therapy approaches and combinations with various chemotherapy agents have not significantly improved survival: median survival for GBM treated with combinations of radiation and chemotherapy still range from only 10 to 15 months.  Because of this very poor prognosis, additional tools for its treatment are desperately needed and even small improvements in survival or quality of life provide a potentially valuable product for patients with malignant brain tumors.

Our first clinical study (link to “Table 2”) established a safe dose range for GliAtak™ and gave encouraging efficacy indications in terms of prolonged survival by several subjects. Since then we have focused our efforts on improving the clinical applicability of the AdV-tk approach by combining it with standard cancer treatments such as surgery and radiation therapy.  Following on the experience from the Phase I study in brain tumors and based on preclinical studies in animal brain tumor models, a Phase Ib/II clinical trial of GliAtak™ in conjunction with radiation, in newly diagnosed malignant gliomas has been developed. This is planned to be conducted at several premier academic centers including Massachusetts General Hospital and Ohio State University.

Results from other investigators using a similar agent have also shown positive trends in efficacy with a doubling in survival time and support going forward with this indication.