With the risk of sounding like a broken record, all the positive indications coming from GVAX are far from being concrete evidence. Showing efficacy and good safety profile in numerous small clinical trials is never a substitution for large phase III trials, which often have contradicting results to earlier clinical trials. Bearing this in mind, there seems to be a great deal of consistency in GVAX’s case.
Chronic Myelogenous Leukemia [CML] is a common type of leukemia, in which certain types of white blood cells multiply in an uncontrolled manner in the bone marrow. Currently, there are approximately 30,000 people living with CML in the US, with more than 4500 cases diagnosed per year. Mortality rate is relatively low, with a five-year survival rate among leukemia patients recently reported to be 89%. The low mortality rate is achieved thanks to continuous treatment with Novartis’ Glivec, a potent inhibitor of the protein BCR-ABL, which was approved in 2001. BCR-ABL has been proven to be essential for the development of the disease, making it a desirable target for inhibition. It is also considered to be an accurate genetic marker for assessing disease stages and progression.
Pancreatic cancer represents a major challenge for the drug development industry. It is the fourth leading cause of cancer death in the United States, with 37,000 people forecasted to be diagnosed every year in the US alone. In its early stages, pancreatic cancer can be treated with surgery (resection), unfortunately, however, there are still no reliable means for early detection of the disease. Consequently, only patients who are diagnosed at the disease’s early stages (20% of diagnosed patients) can actually undergo surgery, with the remaining 80% left with no real alternative. Currently, the mean life expectancy is 15-18 months for patients with early local disease and 3-6 months for patient with advanced metastatic disease. In addition to the lack of tools for early detection, pancreatic cancer cells are naturally resistant to the majority of current chemotherapies and radiation therapies. Thus there is an urgent need for new non-chemo/radio therapeutic treatments targeting both early and advanced stages.
GVAX for prostate cancer is Cell Genesys’ most promising and advanced-stage candidate. It is composed of two prostate cancer cell-lines that contain many common antigens found in metastatic prostate cancer. The need for better treatment for this deadly disease, which is the second leading cause of cancer death in men in the United States, is obvious, especially among patients with advanced-stage disease. GVAX is currently being evaluated in two phase III trials for the treatment of prostate cancer in its advanced (metastatic) stages, after patients cease to respond to hormone therapy and radiation. This state is referred to as metastatic Hormone Refractory Prostate Cancer (mHRPC) and is generally associated with poor prognosis. With a yearly death toll reaching 60,000 men in the US & Europe, the potential of an effective treatment that results in prolonged survival is huge.
One of the most important features in GVAX is its universality. The concept behind GVAX is applicable to numerous cancer types, since theoretically, any type of cancer cell can be genetically modified to secrete GM-CSF, making it a potential cancer vaccine. For example, in order to create GVAX for pancreatic cancer, Cell Genesys chose a pancreatic cancer cell-line, inserted the GM-CSF gene into the cells, irradiated them and the vaccine was ready. For the treatment of leukemia, the company did the same with leukemia cells and so on. However, each type of cancer includes so many types of available cell-lines, that choosing the right cell-line is of extremely high importance. Furthermore, since it is possible to combine more than one cell-line per vaccine, GVAX’s diversity potential, as a platform, is tremendous.
GVAX is similar to traditional vaccines against pathogens like bacteria and viruses. Such traditional vaccines involve the injection of a weakened pathogen or some structural part of it, which is identified and recognized by the immune system. A minor immune response against the vaccine results in immunity towards the pathogen so that next time it enters the body, there will be a swift, strong and systemic response against it. Cell Genesys is taking a similar approach but with some differences. First, the pathogens in this case are cancer cells which are not external pathogens but self derived cells. Second, the vaccine is not given to healthy people but only to people who already have advanced stage prostate cancer. Third, whereas most pathogens can be recognized by the immune system even without any external help, (vaccines simply give the immune system a nice head start), the ultimate goal with GVAX is to make the immune system recognize those cancer cells which it cannot recognize in the first place.
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