Keryx Biopharmaceuticals Announces Positive Phase 2 Study Results of Perifosine as a Single Agent for the Treatment of Advanced
January 29 2010 - 8:30AM
PR Newswire (US)
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: DATASOURCE:
Keryx Biopharmaceuticals, Inc. CONTACT: Lauren Fischer, Director,
Investor Relations, Keryx Biopharmaceuticals, Inc.,
+1-212-531-5962, Web Site: http://www.keryx.com/
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