Geron Announces Publication of Phase 1-2 Telomerase Vaccine Study Results in Patients With Metastatic Prostate
Cancer
MENLO PARK, Calif.--(BUSINESS WIRE)--March 4, 2005--Geron
Corporation (Nasdaq:GERN) announced today the publication of results
of a completed Phase 1-2 clinical trial of its telomerase therapeutic
vaccine administered to patients with metastatic prostate cancer at
Duke University Medical Center. Senior author, Dr. Johannes Vieweg,
and colleagues from Duke published the results in the Journal of
Immunology, available today online at jimmunol.org.
The results show that the vaccination protocol successfully
generated telomerase-specific T-cell responses in 19 of 20 subjects.
The vaccine was well tolerated with no major treatment-related
toxicities. Peak immune responses to vaccination were remarkably high
with 1% to 2% of circulating CD8+ T-cells demonstrating
anti-telomerase specificity. Vaccination was associated with a
significant increase in PSA doubling time and clearance of circulating
tumor cells.
Characteristics of the Immune Response in the Low-Dose Group
Twelve subjects each received three weekly injections of the
vaccine. Eleven responded with significant levels of
telomerase-specific CD8+ T-cells and nine developed significant levels
of telomerase-specific CD4+ T-cells. Subjects who were vaccinated with
a modified vaccine containing a lysosomal targeting sequence responded
with higher frequencies and magnitudes of CD4+ telomerase-specific
T-cells than those vaccinated with the unmodified vaccine. The
telomerase-specific cytotoxic T-lymphocytes (CTLs) isolated from the
peripheral blood of vaccinated study subjects killed telomerase
targets in vitro. CTLs from subjects vaccinated with the modified
vaccine demonstrated greater killing activity against telomerase
targets than CTLs from subjects treated with the unmodified vaccine,
suggesting that the improved CD4+ response augments CTL activity.
Characteristics of the Immune Response in the High-Dose Group
Eight subjects were treated with six weekly injections of the
vaccine to determine if the magnitude of the immune response seen
after three weekly injections could be further enhanced. Six weekly
vaccinations resulted in robust CD8+ T-cell responses that peaked two
to four weeks after the sixth injection, reaching levels of 1% to 2%
of circulating CD8+ T-cells exhibiting anti-telomerase specificity.
This high frequency of antigen-specific T-cell responses is comparable
to those seen after vaccination for infectious diseases that result in
clearance of the infection. The CD8+ telomerase-specific T-cells
generated in patients immunized with the modified vaccine exhibited
characteristics consistent with the development of central T-cell
memory, a finding with important implications for designing an
optimized schedule for boosting injections to prolong the duration of
the vaccine response.
Clinical Response to Vaccination
Five subjects in the high-dose group were available for follow-up
PSA analysis for at least two months after therapy. The median
pre-treatment PSA doubling time in the high-dose group was 2.9 months.
After six vaccinations, the median PSA doubling time increased to 100
months, a statistically significant change (p = 0.04). No significant
change in PSA doubling time was seen in seven evaluable patients from
the low-dose group.
Eighteen subjects were evaluated for the presence of circulating
PSA-expressing prostate cancer cells in their blood before and after
therapy. A total of 10 patients exhibited significant levels of
circulating prostate cancer cells before therapy (four from the
modified vaccine group and six from the unmodified vaccine group).
Four out of four and five out of six of these patients, respectively,
exhibited reduction or clearance of circulating prostate cancer cells
after vaccination.
Implications of the Data
These data show that telomerase vaccination was associated with a
significant impact on PSA doubling time and a reduction or elimination
of circulating tumor cells during the time that a measurable,
telomerase-specific T-cell response was detectable in the patient's
blood. The modified vaccine produced a central T-cell memory response
which should enable recall responses to additional vaccinations. These
observations suggest that continued vaccination (boosting) to maintain
the telomerase-specific T-cell response may enhance clinical impact.
"These results are very exciting," said Dr. Vieweg. "The high
levels of telomerase T-cell immunity generated in these advanced
cancer patients is striking. The temporal association between immunity
and surrogate clinical response suggests a potential clinical impact
of the vaccine. We are currently optimizing the vaccination protocol
to extend the durability of the immune response to telomerase."
"We are obviously pleased with these results," said Thomas B.
Okarma, Ph.D., M.D., Geron's president and chief executive officer.
"Generating high levels of telomerase-specific killer T-cells in
advanced cancer patients without causing toxicity was the primary
objective of this study. We look forward to the results of our current
studies designed to augment the response to vaccination and hopefully,
to provide further evidence of clinical impact."
Geron is a biopharmaceutical company developing and
commercializing three groups of products: i) therapeutic products for
oncology that target telomerase; ii) pharmaceuticals that activate
telomerase in tissues impacted by senescence, injury or degenerative
disease; and iii) cell-based therapies derived from its human
embryonic stem cell platform for applications in multiple chronic
diseases.
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 that involve risks and uncertainties, including, without
limitation, risks inherent in the development and commercialization of
potential products, need for future capital and 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 annual report on Form
10-K for the year ended December 31, 2004.
CONTACT: Geron Corporation
David L. Greenwood, 650-473-7765 |
