Geron Initiates Phase 2 Clinical Trial of Imetelstat in Essential Thrombocythemia
MENLO PARK, Calif., Jan 19, 2011 (BUSINESS WIRE) -- Geron Corporation (GERN)
today announced enrollment of the first patient in a Phase 2 clinical trial to
evaluate the activity of the company's telomerase inhibitor drug, imetelstat
(GRN163L), in patients with essential thrombocythemia (ET). ET is a chronic
disorder that arises in the hematopoietic (blood) stem cells in the bone marrow.
The leukemic stem cells produce aberrant clones of platelet-forming cells
(megakaryocytes), which results in increased numbers of circulating platelets.
"Our Phase 2 clinical trials of imetelstat are focused on malignancies in which
cancer stem cells are thought to play an important role in disease progression,
including breast and lung cancers, multiple myeloma and myeloproliferative
neoplasms, such as essential thrombocythemia," said Stephen M. Kelsey, M.D.,
Geron's executive vice president and chief medical officer, oncology. "In ET, we
think that targeting the leukemic stem cell with imetelstat might impact the
biology of the disease, which is not possible with current standard treatments."
Rationale for the Clinical Trial
Data from Phase 1 clinical trials and preclinical studies of imetelstat provide
the rationale for evaluating the effect of the telomerase inhibitor drug in
patients with ET.
Preclinical studies have demonstrated imetelstat's activity against a broad range
of cancer stem cells from both solid and hematological tumor types. In addition,
leukocytes from patients with ET have notably high telomerase activity and short
telomeres, providing further rationale for evaluating the effects of inhibiting
telomerase with imetelstat in these patients.
Phase 2 Trial Design
The clinical trial is a Phase 2, open-label study of imetelstat as a single agent
in patients with ET who have failed or are intolerant to at least one prior
therapy or who refuse standard therapy, such as hydroxyurea, anagrelide or
interferon-alpha.
The primary efficacy endpoint is best overall hematologic response rate,
determined by a normalization or reduction in platelet counts. Approximately half
of patients with ET have a molecular mutation in the JAK2 or MPL genes. The rate
of molecular response is a secondary endpoint in patients who have one or both of
these mutations at baseline. A molecular response is determined by a reduction in
the percentage of mutant JAK2 or MPL alleles detected in patients' granulocytes.
Safety and tolerability will also be assessed.
Patients in the trial will be stratified based on the presence or absence of
mutations in the JAK2 and MPL genes. Imetelstat is administered at an initial
dose of 7.5 mg/kg weekly in a 28 day treatment cycle. The dose may be escalated
to 9.4 mg/kg and up to a maximum of 11.7 mg/kg weekly, depending on hematologic
response and tolerability. Dose and dosing schedule will be titrated based on
platelet counts. Phase 1 clinical trials of imetelstat have demonstrated that
doses of 7.5 mg/kg and higher allow exposure to imetelstat that exceed the levels
associated with efficacy in xenograft models of human cancers and telomerase
inhibition in tissue samples from patients.
The trial will be conducted at clinical sites in the U.S. and EU. The lead
principal investigator is Srdan Verstovsek, M.D., Ph.D., at The University of
Texas MD Anderson Cancer Center in Houston, Texas. For further information about
this clinical trial, please visit
clinicaltrials.gov.
About Essential Thrombocythemia
Essential thrombocythemia (ET, also known as essential thrombocytosis) is a
chronic blood disorder characterized by increased numbers of platelets in the
blood. These platelets may have abnormal function, which can lead to an increased
risk of thrombotic or hemorrhagic complications. Patients with ET may also
develop myelofibrosis or acute myeloid leukemia.
The precise cause of ET is not known, though approximately half of patients have
mutations in the genes for Janus kinase 2 (JAK2) or, less frequently,
myeloproliferative leukemia (MPL). These gene mutations result in stable
activation of the JAK-STAT signaling pathway and lead to megakaryocytic
hyperplasia and thrombocytosis.
In the United States, there are approximately 7,200 new cases of ET annually.
Life expectancy may be normal in the majority of patients with ET in the first
decade after diagnosis, but subsequently survival is reduced approximately
two-fold compared with the general population. Currently used treatments (such as
hydroxyurea, anagrelide or interferon-alpha) can be effective in reducing
platelet counts in patients with ET, but do not alter the biology or eliminate
the disease. Moreover, clinical resistance or intolerance to these standard
agents occurs in a proportion of patients.
About Telomerase
Telomerase is a critical and broadly applicable tumor target. The enzyme is
expressed in a wide range of malignant tumors, and its activity is essential for
the indefinite replicative capacity of cancer that enables malignant cell growth.
Telomerase is absent or expressed only transiently at low levels in most normal
adult tissues. Telomerase has now also been shown to be a target for cancer stem
cells. Cancer stem cells are rare populations of malignant cells with the
capacity for endless self-renewal found in many types of cancer and are believed
to be responsible for the growth, recurrence and metastasis of tumors. Their
resistance to chemotherapy and conventional anti-cancer agents make them
important targets for novel therapies.
About Imetelstat (GRN163L)
Imetelstat is a lipidated short chain oligonucleotide that binds with high
affinity and specificity to the catalytic site of telomerase, resulting in
competitive inhibition of enzyme activity. Proprietary manufacturing chemistry
and the addition of a 5' lipid chain have enabled the molecule to penetrate cells
and tissues throughout the body.
Imetelstat has demonstrated anti-tumor effects in a wide range of preclinical
xenograft models of human solid and hematological tumors, and potent activity
against cancer stem cells derived from primary patient samples or cancer cell
lines from multiple tumor types.
Imetelstat has been tested in six Geron-sponsored Phase 1 clinical trials at 22
U.S. medical centers treating over 180 patients examining the safety,
tolerability, pharmacokinetics and pharmacodynamics of the drug, alone or in
combination with other standard therapies, in patients with different
hematological and solid tumors.
Two randomized Phase 2 clinical trials of imetelstat have been initiated - the
first in non-small cell lung cancer and a second was recently initiated in breast
cancer. A single arm Phase 2 clinical trial in multiple myeloma is open to
enrollment. All the trials focus on malignancies in which cancer stem cells are
believed to play an important role in disease progression and relapse after
standard therapy. For further information about clinical trials using imetelstat,
please visit clinicaltrials.gov.
About Geron
Geron is developing first-in-class biopharmaceuticals for the treatment of cancer
and chronic degenerative diseases. The company is advancing anti-cancer therapies
through multiple Phase 2 clinical trials in different cancers by targeting the
enzyme telomerase and with a compound designed to penetrate the blood-brain
barrier (BBB). The company is developing cell therapy products from
differentiated human embryonic stem cells for multiple indications, including
central nervous system (CNS) disorders, heart failure, diabetes and
osteoarthritis, and has initiated a Phase 1 clinical trial in spinal cord injury.
For more information, visit geron.com.
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 statements in this press release regarding potential
applications of Geron's telomerase and oncology technology constitute
forward-looking statements that involve risks and uncertainties, including,
without limitation, risks inherent in the development and commercialization of
potential products, uncertainty of clinical trial results or regulatory approvals
or clearances, need for future capital, dependence upon collaborators and
protection 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
September 30, 2010 and annual report on Form 10-K for the year ended December 31,
2009.
SOURCE: Geron Corporation
Geron Corporation
Anna Krassowska, Ph.D., 650-473-7765
Investor and Media Relations
info@geron.com |
