Keryx Biopharmaceuticals Announces Positive Phase 2 Study Results of Perifosine as a Single Agent for the Treatment of Advanced Waldenstrom's Macroglobulinemia
Data Demonstrating a 35% Overall Response Rate with a Median Progression-Free Survival of 12.6 Months in Patients with Relapsed or Relapsed/Refractory Waldenstrom's Macroglobulinemia to be Published in the February 1, 2010 Issue of Clinical Cancer Research
NEW YORK, Jan. 29 /PRNewswire-FirstCall/ -- Keryx
Biopharmaceuticals, Inc. (NASDAQ:KERX) (the "Company") today announced
that an article entitled "Clinical and Translational Studies of a
Phase II Trial of the Novel Oral Akt Inhibitor Perifosine in
Relapsed or Relapsed/Refractory Waldenstrom's Macroglobulinemia,"
reporting Phase 2 data demonstrating the single agent activity of
KRX-0401 (Perifosine) for the treatment of advanced Waldenstrom's
Macroglobulinemia ("Waldenstrom's"), will appear in the February 1,
2010 issue of Clinical Cancer Research. Perifosine, the Company's
oral PI3K/Akt pathway inhibitor is currently being investigated in
a Phase 3 trial, under Special Protocol Assessment, for the
treatment of Advanced Multiple Myeloma. Similar to Multiple Myeloma
and Non-Hodgkin's Lymphoma, Waldenstrom's is a hematologic disease
in which the cancer cells target the bone marrow. There are
currently no drugs FDA approved for the treatment of
Waldenstrom's.
Dr. Irene Ghobrial, Assistant Professor of Medicine, Bing Center
for Waldenstrom's Macroglobulinemia at Dana-Farber Cancer
Institute, led the Phase 2 study in which thirty-seven patients
were treated with perifosine 150 mg daily for 6 cycles. In this
study, 41% of the patients had 3 or more lines of prior therapy and
78% had 2 or more prior lines of therapy. Such prior therapies
include nucleoside analogues, bortezomib, alkylating agents and
rituximab, which are not approved for, but are often used in the
treatment of Waldenstrom's. The median % involvement of the bone
marrow with lymphoplasmacytic cells was 70%, indicating advanced
disease. Stable or responding patients were allowed to continue
therapy until progression. Of the 37 patients, 4 achieved a partial
response (11%), 9 achieved a minimal response (24%), and 20 showed
stable disease (54%). Overall, 89% (33/37) of patients treated with
single agent perifosine were reported to have stable disease or
better, while 11% (4 patients) demonstrated progression. The median
progression-free survival in the study was 12.6 months (90% C.I.
(10.2, 22.7)), with a median overall survival of 26 months (90%
C.I. (26 - upper limit not reached)). Perifosine was generally
well-tolerated with gastrointestinal symptoms and fatigue reported
as the most common adverse events related to therapy.
Also described in the article are translational studies using
gene expression profiling and immunohistochemistry on pre- versus
post-treatment patient samples conducted by Dr. Ghobrial. Results
showed that in the majority of samples tested, there was a
significant reduction of phospho-GSK3/beta (downstream from Akt)
using immunohistochemistry. Similarly, results demonstrated that
perifosine significantly inhibited the expression of multiple
members of the NF-kB family of genes, confirming previous in vitro
studies showing activity of perifosine targeting this
pathway.
"Perifosine as a single agent holds great promise in the
treatment of patients with relapsed/refractory Waldenstrom's
Macroglobulinemia," commented Dr. Ghobrial, who continued,
"Responses were durable and occurred rapidly. The progression-free
survival of 12.6 months is considered long compared to other
targeted agents used in a similar population such as bortezomib
(Velcade®), where the median time to progression was reported
at 7.9 months. We look forward to further evaluating perifosine's
promise in this disease, either as a single agent or in combination
with agents such as rituximab (Rituxan®) or bortezomib."
Ron Bentsur, Chief Executive Officer of Keryx
Biopharmaceuticals, remarked "We are very excited to see this
single agent activity of perifosine, which further demonstrates its
potential as a targeted agent. This Waldenstrom's data is of
particular interest because, similar to multiple myeloma,
Waldenstrom's is also a bone-marrow-based hematologic tumor.
Moreover, Waldenstrom's represents an unmet medical need for which
there are no approved drugs and therefore could potentially provide
us with an additional registration strategy for perifosine.
Finally, we wish to thank Dr. Ghobrial and her impressive team of
investigators for their dedication to this Waldenstrom's
program."
Perifosine is currently in a Phase 3 trial, under Special
Protocol Assessment (SPA), for the treatment of relapsed/refractory
multiple myeloma, with Orphan Drug Status and Fast Track
Designation granted.
KRX-0401 (perifosine) is in-licensed by Keryx from Aeterna
Zentaris Inc. (Nasdaq: AEZS; TSX: AEZ) in the United States, Canada
and Mexico.
About Waldenstrom's Macroglobulinemia
Waldenstrom's Macroglobulinemia is a distinct
lymphoproliferative disorder characterized by bone marrow
infiltration with lymphoplasmacytic cells, along with an IgM
monoclonal gammopathy. Waldenstrom's affects an estimated 1,500
patients annually in the U.S. Despite advances in the therapy of
Waldenstrom's, the disease remains incurable, thereby necessitating
the development of novel therapeutics. There are no drugs currently
FDA approved for Waldenstrom's, with nucleoside analogues, the
proteasome inhibitor bortezomib (Velcade®), alkylating agents
(chlorambucil) and rituximab (Rituxan®) often used to treat the
disease.
About KRX-0401 (Perifosine)
KRX-0401 (perifosine) is a novel, potentially first-in-class,
oral anti-cancer agent that inhibits the phosphoinositide 3-kinase
(PI3K)/Akt pathway, a key signaling cascade that has been shown to
induce cell growth and cell transformation. KRX-0401 has
demonstrated both safety and clinical efficacy in several tumor
types, both as a single agent and in combination with novel
therapies. KRX-0401 also modulates a number of other key signal
transduction pathways, including the JNK pathway, which are
pathways associated with programmed cell death, cell growth, cell
differentiation and cell survival. The effects of perifosine on Akt
are of particular interest because of the importance of this
pathway in the development of most cancers, with evidence that it
is often activated in tumors that are resistant to other forms of
anticancer therapy, and the difficulty encountered thus far in the
discovery of drugs that will inhibit this pathway without causing
excessive toxicity. High levels of activated Akt (pAkt) are seen
frequently in many types of cancer and have been correlated with
poor prognosis.
Keryx has been granted a Special Protocol Assessment (SPA) from
the FDA for the Phase 3 study of perifosine in multiple myeloma.
Additionally, the FDA has granted perifosine Orphan Drug and Fast
Track designations in multiple myeloma.
About Keryx Biopharmaceuticals, Inc.
Keryx Biopharmaceuticals is focused on the acquisition,
development and commercialization of medically important
pharmaceutical products for the treatment of life-threatening
diseases, including cancer and renal disease. Keryx is developing
KRX-0401 (perifosine), a novel, potentially first-in-class, oral
anti-cancer agent that inhibits the phosphoinositide 3-kinase
(PI3K)/Akt pathway, a key signaling cascade that has been shown to
induce cell growth and cell transformation. KRX-0401 has
demonstrated both safety and clinical efficacy in several tumor
types, both as a single agent and in combination with novel
therapies. KRX-0401 also modulates a number of other key signal
transduction pathways, including the JNK pathway, which are
pathways associated with programmed cell death, cell growth, cell
differentiation and cell survival. KRX-0401 is currently in a Phase
3 trial, under Special Protocol Assessment (SPA), in multiple
myeloma, and in Phase 2 clinical development for several other
tumor types. Keryx is also developing Zerenex(TM) (ferric citrate),
an oral, iron-based compound that has the capacity to bind to
phosphate and form non-absorbable complexes. The Phase 3 clinical
program of Zerenex in the treatment for hyperphosphatemia (elevated
phosphate levels) in patients with end-stage renal disease is
pending commencement under an SPA agreement with the FDA. Keryx is
headquartered in New York City.
Cautionary Statement
Some of the statements included in this press release,
particularly those anticipating future clinical trials and business
prospects for KRX-0401 (perifosine), 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 and cost-effectively complete clinical
trials for KRX-0401, including, but not limited to, the indication
of Waldenstrom's Macroglobulinemia; 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 undertake 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 found on
our website is not incorporated by reference into this press
release and is included for reference purposes only.
KERYX CONTACT: Lauren Fischer Director, Investor Relations Keryx Biopharmaceuticals, Inc. Tel: 212.531.5962 E-mail: lfischer@keryx.com
Source: Keryx Biopharmaceuticals, Inc.
CONTACT: Lauren Fischer, Director, Investor Relations,
Keryx
Biopharmaceuticals, Inc., +1-212-531-5962, lfischer@keryx.com
Web Site: http://www.keryx.com/
Posted: January 2010
