Early Results of Phase 2 Trial of Perifosine (KRX-0401) for the Treatment of Recurrent Malignant Gliomas Presented at the 12th A
November 19 2007 - 8:47AM
PR Newswire (US)
Poster presentation highlights response rate in subset of patients
with Anaplastic Gliomas NEW YORK, Nov. 19 /PRNewswire-FirstCall/ --
Keryx Biopharmaceuticals, Inc. (NASDAQ:KERX) today announced that
early results of a phase II single agent trial of perifosine
(KRX-0401) in patients with recurrent malignant gliomas was
presented in a poster presentation on Saturday, November 17, 2007
at the 12th Annual Scientific Meeting of the Society for
Neuro-Oncology, held in Dallas, Texas. The poster, entitled "A
Phase II Trial of Perifosine for Recurrent/Progressive Malignant
Gliomas, provided an update on the clinical activity of single
agent perifosine in patients with malignant glioblastoma (GBM) and
malignant anaplastic gliomas (AA). Ph II Study - Interim Results
Twenty-five patients with advanced malignant gliomas were treated
with a loading dose of 600 mg (150mg x 4) followed by 100 mg daily
dose of perifosine. Patients must have failed prior radiation
therapy and have shown unequivocal evidence for tumor progression
by MRI or CT scan. There was no limitation on the number of prior
relapses or prior therapies and patients with a KPS greater than or
equal to 50 were eligible. Patients were not allowed to take
enzyme-inducing anti-epileptic drugs (EIAED's). Response was
measured by the MacDonald Criteria (PR greater than or equal to 50%
decrease in bidirectional tumor area and SD = between 25% worse to
50% better). Patients were broken out into two groups with results
as follows: Malignant Glioma N Evaluable Partial Stable Overall (PR
Response Disease + SD) All Patients 25 20 2 (10%) 4 (20%) 6 (30%)
Glioblastoma 16 14 0 2 (14%) 2 (14%) Anaplastic Glioma 9 6 2* (33%)
2 (33%) 4 (66%) *1 Patient with Anaplastic Astrocytoma and 1
Patient with Anaplastic Oligodendroglioma The median Progression
Free Survival (PFS) and Overall Survival (OS) in the Anaplastic
Glioma group was 9 wks (range 2 - 50 wks) and 49 wks respectively.
Toxicity was minimal with the following reported events (n): grade
1 nausea (1), grade 1 diarrhea (1), grade 2 pain (1) and grade 4
gout exacerbation (1). The study was designed to enroll at least 12
evaluable GBM patients and at least 10 evaluable AA patients. If at
least 1 patient achieves 6 month PFS, the study would continue to
enroll an additional subset of patients. Therefore, the GBM arm has
been halted and the AA arm will continue to enroll. Final study
updates will be reported at a future meeting. I. Craig Henderson,
MD, President of Keryx Biopharmaceuticals, commented "We want to
further evaluate the role of perifosine in patients with malignant
gliomas. The single agent activity observed in patients with
anaplastic gliomas is of great interest as these patients are in
need of additional therapies. We look forward to expanding this
patient cohort." For copies of the poster which was presented
during the meeting, please contact Keryx Biopharmaceuticals.
Perifosine (KRX-0401) Mechanism of Action and Profile Perifosine
has been shown to inhibit or otherwise modify signaling through a
number of different signal transduction pathways including Akt,
MAPK, and JNK. Akt isoforms have been found to be overexpressed in
renal, breast, prostate, and pancreatic cancers. Elevated levels of
pAkt have been correlated with poor prognosis in patients with
gastric, hepatocellular, endometrial, prostate, renal cell and head
and neck cancers, as well as glioblastoma. The majority of tumors
expressing high levels of pAkt were high-grade, advanced stage or
had other features associated with poor prognosis. The effects of
perifosine on Akt are of particular interest because of 1) the
importance of this pathway in the development of most cancers; 2)
the evidence that it is often activated in tumors that are
resistant to other forms of anticancer therapy; and 3) and the
difficulty encountered thus far in the discovery of drugs that will
inhibit this pathway without causing excessive toxicity. To date,
over 1,500 patients have been treated with perifosine in trials
conducted both in the US and Europe. Its safety profile is
distinctly different from that of most cytotoxic agents. It does
not cause myelosuppression (depression of the immune system) or
alopecia (hair loss) like many currently available treatments for
cancer. In phase I/II trials it has induced tumor regressions
and/or caused disease stabilization in a variety of tumor types.
Responding patients, including stable disease, have been treated
for months to almost 3 years, on both the daily and weekly
schedule. KRX-0401 (perifosine) is in-licensed by Keryx from
Aeterna Zentaris, Inc. (Nasdaq: AEZS; TSX: AEZ) in the United
States, Canada and Mexico. About Malignant Gliomas The American
Cancer Society estimates that 20,500 malignant tumors of the brain
or spinal cord (11,170 in men and 9,330 in women) will be diagnosed
during 2007 in the United States. Approximately 12,740 people
(7,150 men and 5,590 women) will die from these malignant tumors.
This type of cancer accounts for approximately 1.3% of all cancers
and 2.2% of all cancer-related deaths. Both adults and children are
included in these statistics. About Keryx Biopharmaceuticals, Inc.
Keryx Biopharmaceuticals, Inc. is focused on the acquisition,
development and commercialization of medically important, novel
pharmaceutical products for the treatment of life-threatening
diseases, including diabetes and cancer. Keryx's lead compound
under development is Sulonex(TM) (sulodexide oral gelcap),
previously referred to as KRX-101, a first-in-class, oral
heparinoid compound for the treatment of diabetic nephropathy, a
life-threatening kidney disease caused by diabetes. Sulonex is in a
pivotal Phase 3 and Phase 4 clinical program under a Special
Protocol Assessment with the Food & Drug Administration.
Additionally, Keryx is developing Zerenex(TM), an oral, iron- based
compound that has the capacity to bind phosphate and form
non-absorbable complexes. Zerenex is currently in Phase 2 clinical
development for the treatment of hyperphosphatemia (elevated serum
phosphorous levels) in patients with end-stage renal disease. Keryx
is also developing clinical-stage oncology compounds, including
KRX-0401, a novel, first-in-class, oral anti-cancer agent that
modulates Akt, a protein in the body associated with tumor survival
and growth, and a number of other key signal transduction pathways,
including the JNK and MAPK pathways, which are pathways associated
with programmed cell death, cell growth, cell differentiation and
cell survival. KRX-0401 is currently in Phase 2 clinical
development for multiple tumor types. Keryx also has an active
in-licensing and acquisition program designed to identify and
acquire additional drug candidates. Keryx is headquartered in New
York City. Cautionary Statement Some of the statements included in
this press release, particularly those anticipating future the
financial performance and clinical and business prospects for
KRX-0401, may be forward-looking statements that involve a number
of risks and uncertainties. For those statements, we claim the
protection of the safe harbor for forward-looking statements
contained in the Private Securities Litigation Reform Act of 1995.
Among the factors that could cause our actual results to differ
materially are the following: our ability to successfully complete
the Phase 1 and Phase 2 clinical trials for KRX-0401; we may not be
able to meet anticipated development timelines for KRX-0401 due to
recruitment, clinical trial results, manufacturing capabilities or
other factors; and other risk factors identified from time to time
in our reports filed with the Securities and Exchange Commission.
Any forward-looking statements set forth in this press release
speak only as of the date of this press release. We do not intend
to update any of these forward-looking statements to reflect events
or circumstances that occur after the date hereof. This press
release and prior releases are available at http://www.keryx.com/.
The information in our website is not incorporated by reference
into this press release and is included as an inactive textual
reference only. KERYX CONTACT: Lauren Fischer Director - Investor
Relations Keryx Biopharmaceuticals, Inc. Tel: 212.531.5965 E-mail:
DATASOURCE: Keryx Biopharmaceuticals, Inc. CONTACT: Lauren Fischer,
Director - Investor Relations, Keryx Biopharmaceuticals, Inc.,
+1-212-531-5965, Web site: http://www.keryx.com/
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