AEterna Zentaris Partner Keryx Announces Positive Phase 2 Results for Perifosine as a Single Agent for the Treatment of Advanced
January 29 2010 - 8:35AM
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 the Journal of Clinical
Cancer Research QUEBEC CITY, Jan. 29 /PRNewswire-FirstCall/ --
AEterna Zentaris Inc. (Nasdaq: AEZS; TSX: AEZ) (the "Company"), a
late-stage drug development company specialized in oncology and
endocrinology, 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 perifosine (KRX-0401)
for the treatment of advanced Waldenstrom's Macroglobulinemia
("Waldenstrom's"), will appear in the February 1, 2010 issue of the
Journal 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 Multiple Myeloma. Like 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 FDA
approved drugs for the treatment of Waldenstrom's. Keryx
Biopharmaceuticals, Inc. (NASDAQ:KERX) is AEterna Zentaris' partner
and licensee for perifosine in the United States, Canada and
Mexico. Perifosine is also out-licensed to Handok in South Korea
while AEterna Zentaris retains rights for the rest of the world.
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 37 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/b (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(R)) 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 or bortezomib." Juergen Engel,
President and CEO of AEterna Zentaris stated, "We are very pleased
with these results as they provide additional evidence of
perifosine's potential as a novel approach in treating multiple
types of cancer, both as a single agent and in combination therapy.
We now look forward to the future late-stage development of this
compound in Waldenstrom's Macroglobulinemia, metastatic colon
cancer as well as in multiple myeloma, for which perifosine is
currently in an ongoing Phase 3 registration trial." 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 currently no FDA
approved drugs for Waldenstrom's, with nucleoside analogues, the
proteasome inhibitor bortezomib (Velcade(R)), alkylating agents
(chlorambucil) and rituximab (Rituxan(R)) often used to treat the
disease. About Perifosine Perifosine is a novel, potentially
first-in-class, oral anticancer agent that modulates Akt and a
number of other key signal transduction pathways including the JNK
pathway, all of 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. Perifosine is
currently in a Phase 3 trial, under Special Protocol Assessment
(SPA), in multiple myeloma for which it has received Orphan Drug
and Fast Track designations from the FDA in this indication.
Perifosine is also in Phase 2 clinical trials for several other
tumor types. About AEterna Zentaris Inc. AEterna Zentaris Inc. is a
late-stage drug development company specialized in oncology and
endocrinology. News releases and additional information are
available at http://www.aezsinc.com/. Forward-Looking Statements
This press release contains forward-looking statements made
pursuant to the safe harbor provisions of the U.S. Securities
Litigation Reform Act of 1995. Forward-looking statements involve
known and unknown risks and uncertainties, which could cause the
Company's actual results to differ materially from those in the
forward-looking statements. Such risks and uncertainties include,
among others, the availability of funds and resources to pursue
R&D projects, the successful and timely completion of clinical
studies, the ability of the Company to take advantage of business
opportunities in the pharmaceutical industry, uncertainties related
to the regulatory process and general changes in economic
conditions. Investors should consult the Company's quarterly and
annual filings with the Canadian and U.S. securities commissions
for additional information on risks and uncertainties relating to
the forward-looking statements. Investors are cautioned not to rely
on these forward-looking statements. The Company does not undertake
to update these forward-looking statements. We disclaim any
obligation to update any such factors or to publicly announce the
result of any revisions to any of the forward-looking statements
contained herein to reflect future results, events or developments
except if we are required by a governmental authority or applicable
law. DATASOURCE: AETERNA ZENTARIS INC. CONTACT: Investor Relations:
Dennis Turpin, SVP and CFO, (418) 652-8525 ext. 242, ; Media
Relations: Paul Burroughs, Director of Communications, (418)
652-8525 ext. 406,
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