>>ORLANDO, Fla., May 19 /PRNewswire-FirstCall/ -- Cell Genesys, Inc. (Nasdaq: CEGE - News) today reported encouraging long term survival data from a Phase II multicenter clinical trial of GVAX® prostate cancer vaccine which demonstrates a dose-dependent trend toward prolonged survival in patients with hormone refractory prostate cancer metastatic to bone. In the 34-patient study, seven of 10 (70 percent) patients receiving the higher dose level of the vaccine are alive 2.5 years after treatment (median survival greater than 30 months). Of the 24 patients receiving the lower dose of the vaccine, nine of 22 patients (41 percent) are alive 2.5 years after treatment (median survival 22 months), and two were lost to follow-up. These results compare favorably to the reported median survival of seven to 11 months for hormone refractory prostate cancer patients with bone metastases who are treated with chemotherapy, the current standard of care for this patient group. The dose-dependent improvement in survival was consistent with a previously reported improvement in time to disease progression measured by both radiologic and prostate-specific antigen (PSA) endpoints also in favor of the high dose group. Treatment with GVAX® vaccine was safe and well tolerated. These data were presented at the American Society of Clinical Oncology (ASCO) Meeting in Orlando, FL by Jonathan Simons, M.D., of Emory University.
The study reported at ASCO employed a six-month treatment regimen in which patients received an initial "priming" dose of GVAX® prostate cancer vaccine followed by 12 biweekly "booster" doses using either a high dose or threefold lower dose regimen. The two dose groups were comparable with respect to disease stage, duration and prior treatment for their prostate cancer as well as other demographic criteria. The vaccine, which is a non patient-specific, "off-the-shelf" product was administered by an intradermal injection into the skin of the arms and legs in an outpatient clinic setting. Patients were observed for evidence of vaccine efficacy and safety using standard clinical and radiologic tests. No other cancer therapies aside from the GVAX® vaccine were administered during either the six-month treatment or post treatment follow-up period.
"These encouraging data have prompted Cell Genesys to plan a Phase III trial of GVAX® prostate cancer vaccine which we expect to initiate in the first half of 2003. Prior to initiating this trial, we will have the necessary manufacturing and quality control infrastructure in place to ensure the highest quality of product will be available for our Phase III trials and potential subsequent market launch," stated Joseph J. Vallner, Ph.D., president and chief operating officer of Cell Genesys. "Given the data presented today, we believe that GVAX® prostate cancer vaccine may provide an attractive alternative to chemotherapy which is the only treatment option currently available to patients with metastatic hormone refractory prostate cancer."
Based on the compelling dose response data in the Phase II trial of GVAX® prostate cancer vaccine, Cell Genesys is currently conducting Phase I/II clinical trials to evaluate a high potency GVAX® prostate cancer vaccine that secretes five to tenfold greater levels of the immune stimulatory hormone which is an active ingredient of all GVAX® products. These ongoing trials are also testing alternate schedules of administration for the high potency product and will be completed prior to its advancement into Phase III trials during the first half of 2003.
In preparation for the company's Phase III GVAX® prostate cancer vaccine clinical trial, Cell Genesys is constructing a 41,000 square-foot manufacturing facility in nearby Hayward, CA, which will be used for the manufacturing of multiple GVAX® cancer vaccine products for large scale clinical trials and potential market launch. The new GMP (Good Manufacturing Practices) facility, which is expected to be on-line in late 2002, is in addition to the company's two other GMP manufacturing facilities -- a facility in San Diego, CA for manufacturing the company's viral based products such as oncolytic virus therapies, and a facility under construction in Memphis, TN for manufacturing the company's patient-specific GVAX® lung cancer vaccine, which is expected to enter Phase III trials in late 2002.
Cell Genesys' GVAX® cancer vaccines, which are designed to stimulate an immune response against the patient's tumor, are comprised of tumor cells that have been irradiated and genetically modified to secrete GM-CSF, an immune hormone which plays a key role in stimulating the body's immune response to vaccines. GVAX® cancer vaccines have demonstrated antitumor effects against every type of human cancer against which they have been tested to date and are currently being evaluated in five types of cancer -- lung, prostate, pancreatic, leukemia and myeloma. Currently, Cell Genesys is evaluating non patient-specific, off-the-shelf GVAX® vaccines for prostate cancer and pancreatic cancer and patient-specific, individualized vaccines for lung cancer, leukemia and myeloma.
GVAX® prostate cancer vaccine is one of two types of products targeting prostate cancer currently in clinical development at Cell Genesys. In addition to GVAX® prostate cancer vaccine which is an immune-based therapy administered as a single agent, Cell Genesys is also developing oncolytic virus therapies for prostate cancer which are genetically modified adenoviruses engineered to selectively destroy prostate cancer cells and which will be administered in combination with radiation or chemotherapy. During 2002, it is projected that in the U.S. alone, approximately 189,000 new cases of prostate cancer will be diagnosed, approximately one million men are living with prostate cancer, and about 30,200 men will die of this disease. Prostate cancer is the second leading cause of cancer death in men, exceeded only by lung cancer.<<
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Comparing this superficially with Abbott's Atrasentan in a similar (though much larger population), GVAX kicked butt. Caveats: 1) Abbott's trial was not powered for survival. 2) In Abbott's trial the controls survived much longer, thus making Atrasentan results look less dramatic. The difference was that no other therapies were administered during the GVAX trial, while in the Atrasentan trial "All patients also received standard of care, which is a continuation of hormone therapy plus supportive care, when appropriate." So not an apples to apples comparison. If one assumes a similar control group for GVAX, it still beat Atrasentan, but that might be because the Atrasentan cohort hasn't been studied long enough yet; the PR is not clear about that, and follow-up data may show the survival times getting longer. Regardless, using the same control group, GVAX still seems to offer a noticeable survival benefit. The relevant snip from Abbott's PR follows:
>>The data, presented by Michael Carducci, M.D., associate professor at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and a co-lead investigator in the study, show that men who fully adhered to the protocol and received atrasentan experienced a median survival benefit of approximately three months compared to those who received placebo. All patients also received standard of care, which is a continuation of hormone therapy plus supportive care, when appropriate. Atrasentan is currently under further investigation in two, large, multinational Phase III clinical trials.
"Although this study was not designed to assess survival, we are optimistic about the potential survival advantage demonstrated with atrasentan in this trial," said Joel Nelson, M.D. professor and chairman of urology, University of Pittsburgh Cancer Institute, and the other co-lead investigator in the study. "These data further substantiate the potential clinical benefit of atrasentan for men with advanced prostate cancer. We look forward to further understanding the potential for atrasentan based on ongoing Phase III trials."
The data presented are from a Phase II study of 288 patients randomized to receive an oral, once-daily dose of 2.5 mg or 10 mg of atrasentan, or placebo together with standard of care. All patients participating in the study had prostate cancer that had metastasized (spread beyond the prostate gland) and was hormone-refractory (no longer responded to hormone therapy). After completion of the Phase II study, patients were eligible to receive atrasentan therapy in an open-label extension study.
In 244 evaluable patients, average survival was 583 days for those who received atrasentan compared to 500 days for those who received standard of care (p<0.05). The evaluable group, which was defined prior to study unblinding, included patients who met prespecified inclusion criteria and did not have any major violations of the study protocol. A similar survival trend was noted in the intent-to-treat group (which included all 288 patients originally enrolled in the study, regardless of meeting inclusion criteria or protocol violations) . . .
Adverse events were mild to moderate in severity. The most common adverse events associated with the 10 mg dose of atrasentan compared to placebo were peripheral edema (swelling, 35 percent vs. 14 percent), rhinitis (runny nose, 28 percent vs. 13 percent) and headache (20 percent vs. 10 percent) and were associated with only one treatment discontinuation.<<
No mention of adverse affects of GVAX in CEGE's PR.
If I've made any mistakes, obvious or otherwise, in this analysis, please, please correct me. I must say, that ethically, since the addition of standard of care treatment obviously helps, I like that design -- used by Abbott in their trial. But it does muddy the results a bit.
Cheers, Tuck |
