Monday June 7, 7:30 AM EDT
MENLO PARK, Calif., Jun 7, 2004 (BUSINESS WIRE) -- Geron Corporation (GERN) today announced the presentation of new positive results from a Phase I/II clinical trial of its telomerase therapeutic vaccine in metastatic prostate cancer. The presentation was given yesterday at the American Society of Clinical Oncology (ASCO) annual meeting in New Orleans, Louisiana, by the principal investigator of the trial, Johannes Vieweg, M.D., Associate Professor of Urology and Associate Professor of Immunology at Duke University Medical Center.
Vaccination Induces Vigorous Immune Responses Without Side Effects
Dr. Vieweg's presentation summarized the laboratory and clinical findings from the 20 patients who have been enrolled in the trial. Nineteen of the twenty patients responded to the vaccine by generating telomerase specific cytotoxic T-cells. None of the patients experienced any treatment-related side effects. Patients in the high dose group (those receiving 6 weekly injections) responded with a dramatic telomerase-specific T-cell response that increased over the treatment course and peaked 2 to 4 weeks after the final dose. Peak levels of their telomerase-specific T-cells were remarkably high, ranging from 0.9% to 1.8% of the total circulating cytotoxic T-cell pool. Telomerase-specific T-cells were detected for at least 16 weeks after vaccination.
High Dose Patient Group Shows Statistically Significant Increase in PSA Doubling Time
Although designed primarily as a safety study, it was observed that patients in the high dose group experienced a statistically significant increase in their PSA doubling time during the post-vaccination period when telomerase-specific T-cells were present. PSA doubling time (the rate of increase in PSA levels, expressed as the time it would take for a patient's PSA levels to double) is a clinically used surrogate marker of disease progression. The median PSA doubling time in the high dose group before vaccination was 2.9 months. After vaccination, the median PSA doubling time improved to 100 months. Moreover, of the 10 patients who were found to have elevated levels of circulating prostate cancer cells at the onset of the study, 9 exhibited substantial reduction or complete clearance of their circulating tumor cells during the period in which telomerase specific T-cells were detected in their blood.
"These results are important," said Dr. Vieweg. "First, we are confident in the reliability of the ex vivo cell processing protocol. Second, the effectiveness of the vaccine is very high, with 19 of 20 subjects responding appropriately with the generation of telomerase-specific cytotoxic T-cells in their blood. The clinical utility of the vaccine-induced anti-telomerase immunity is reflected by the clearance of circulating prostate cancer cells from the blood and by the statistically significant prolongation of the PSA doubling time in the patients in the high dose group, which correlated with the time course of anti-telomerase immunity. We are eager to now begin the next series of studies in which patients will also receive monthly booster vaccinations in order to extend the period of telomerase immunity and to establish durable clinical effectiveness."
Significance of the Findings
The goal of therapeutic cancer vaccines is to instruct the patient's own immune system to attack cancer cells while sparing normal cells, by exposing the immune system to a substance (an antigen) that is specific to the cancer cells, thus inducing an immune response to cancer cells that present that antigen. As reported in several publications, academic groups using alternative methods to generate anti-telomerase T-cells in cancer patients have demonstrated that such cells exhibit killing activity against renal, breast, colon, lung, melanoma and hematologic cancers, consistent with the widespread expression of telomerase in all major cancer types. The Duke clinical trial uses an ex vivo (outside the body) process in which dendritic cells (the most efficient antigen-presenting cells in the body) are isolated from the patient's blood, pulsed with telomerase RNA, and then used to vaccinate the patient. With the platform used at Duke, sufficient cells can be generated from one blood draw to manufacture 12 to 15 doses of vaccine.
The new data presented yesterday show that increasing the vaccination schedule from 3 to 6 weekly injections resulted in a significant increase in the level and duration of telomerase specific cytotoxic T-cells without any apparent clinical or laboratory toxicity. The clinical effectiveness of these circulating telomerase cytotoxic T-cells was suggested by two independent surrogate markers which correlated fully with the kinetics of the induction of telomerase immunity: 1) clearance of circulating prostate cancer cells from the patient's blood and 2) significant prolongation of the PSA doubling time.
The ex vivo dendritic cell technology used in this clinical trial, developed at Duke by Dr. Vieweg and Dr. Eli Gilboa and their colleagues, was licensed by Duke to Merix Bioscience, Inc., which has supplemented it with other related technologies. Geron recently acquired from Merix co-exclusive rights to use the Merix technology in cancer vaccines using defined antigens, including telomerase. Geron holds numerous patents on telomerase and its use, including an issued U.S. patent covering the use of telomerase in an ex vivo cancer vaccine. Geron thus has exclusive rights for the use of telomerase in vaccines such as the one tested in the Duke trial.
"We are very pleased with these results, which confirm the potency and utility of the dendritic cell-based telomerase vaccine," said Thomas B. Okarma, Ph.D., M.D., Geron's president and chief executive officer. "This is an extremely vigorous T-cell response for a cancer vaccine trial. These high levels of T-cell responses are comparable to those seen after vaccination for infectious diseases that result in clearance of the infection. The absence of toxicity confirms the specificity of the anti-telomerase T-cells and the selective expression of telomerase in cancer cells. The most exciting aspect of the new data is the impact of the vaccine on clearing metastasizing prostate cancer cells and on prolonging patient's PSA doubling times. Our next step is to prolong the anti-telomerase immunity by the use of intermittent vaccination booster injections. We believe that we are developing a vaccination approach that will prove to be clinically meaningful not only in prostate cancer but in other tumor types as well."
The clinical trial conducted by Duke was funded by a grant from the National Institutes of Health.
Geron is a biopharmaceutical company focused on developing and commercializing therapeutic and diagnostic products for cancer based on its telomerase technology, and cell-based therapeutics using its human embryonic stem cell technology.
This news release may contain forward-looking statements made pursuant to the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that such forward-looking statements in this press release regarding potential applications of Geron's technology constitute forward-looking statements involving risks and uncertainties, including, without limitation, risks inherent in the development and commercialization of potential products, reliance on collaborators, need for additional capital, need for regulatory approvals or clearances, and the maintenance of our intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements. Additional information on potential factors that could affect our results and other risks and uncertainties are detailed from time to time in Geron's periodic reports, including the quarterly report on Form 10-Q for the quarter ended March 31, 2004.
SOURCE: Geron Corporation
CONTACT: Geron Corporation
David L. Greenwood, 650-473-7765
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