QUÉBEC CITY, June 5, 2012
/PRNewswire/ - Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZ)
(the "Company") today announced that Phase 1 trial results for
the Company's oral anticancer compound, perifosine, in multiple
myeloma, have been published in the online May 2012 issue of the British Journal of
Haematology. The article outlines the safety profile and
encouraging clinical activity of perifosine when combined with
lenalidomide and dexamethasone in relapsed and relapsed/refractory
multiple myeloma.
The Study
Thirty-two patients were enrolled in this single-arm, open label
Phase 1 trial across 4-dose cohorts. Patients received escalating
doses of perifosine 50-100 mg daily and lenalidomide
15-25 mg once daily on days 1-21 of each 28-day cycle,
plus dexamethasone 20-40 mg weekly thereafter, as indicated.
The primary objectives of the trial were to determine the safety,
maximum tolerated dose (MTD) and response -rate (clinicaltrials.gov
NCT00415064).
Results
Among 30 evaluable patients for efficacy, 73% achieved a minimal
response or better, including 50% with a partial response or
better. Median progression-free survival was 10.8 months and
median overall survival was 30.6 months.
Among the 31 evaluable patients for safety and tolerability, the
most common all-causality grade 1-2 adverse events were
fatigue (48%) and diarrhea (45%), and grade 3-4 adverse events were
neutropenia (26%), hypophosphataemia (23%), thrombocytopenia (16%),
and leucopenia (13%). No grade 3-4 peripheral neuropathy or deep
vein thrombosis were reported.
Exploratory pharmacodynamic study data suggest that the clinical
efficacy of perifosine + lenalidomide + dexamethasone is positively
associated with phospho-Akt; the activity of the 3-drug combination
appeared to be greater in patients with higher baseline
phospho-Akt. Although this observation is based on just a few
patients, the correlative data could represent the first steps
towards the rational selection of individualized therapy with Akt
inhibitors. The data also suggest that perifosine may be
particularly effective in patients with Akt-dependent multiple
myeloma, a subgroup of multiple myeloma (Zollinger et
al,2008). Additional studies are ongoing to investigate the
potential relationship between perifosine activity and phospho-Akt.
Findings may show whether patients with an activated Akt genotype
would benefit in particular from the addition of perifosine,
therefore raising the possibility of individualized therapy
according to a patient's phospho-Akt status. The authors concluded:
"Perifosine + lenalidomide + dexamethasone was well tolerated and
demonstrated encouraging clinical activity in relapsed and
relapsed/refractory multiple myeloma".
Juergen Engel, PhD, President and
CEO of Aeterna Zentaris stated, "Results of this study including
the new exploratory pharmacodynamic data are one of the reasons
which encouraged us to continue our Phase 3 study with perifosine
in multiple myeloma."
These data were presented previously; see Blood (ASH Annual
Meeting Abstracts) 116: 2010 (abstract 3064).
About Multiple Myeloma
Multiple myeloma is the second most common blood cancer.
According to Decision Resources, there will be approximately
180,830 cases of multiple myeloma diagnosed in the main G7 markets
in 2012. Research shows that the majority of patients diagnosed
with multiple myeloma are age 65 and older. Approximately 2,500
more males are diagnosed with this cancer than females each
year.
About Perifosine
Perifosine is a novel, oral anticancer compound that inhibits
Akt activation in the phosphoinositide 3-kinase (PI3K) pathway. It
works by interfering with membranes of cancer cells, thereby
inhibiting Akt signaling which then affects cell death, growth,
differentiation and survival. Perifosine is currently in a Phase 3
trial in multiple myeloma. In this indication, it has been granted
Orphan Drug and Fast Track designations by the Food and Drug
Administration. It has also received positive Scientific Advice and
Orphan Medicinal Product designation from the European Medicines
Agency. Rights for perifosine have been out licensed to Yakult
Honsha Co. Ltd. for Japan, to
Handok Pharmaceuticals Co. Ltd. for Korea and to Hikma
Pharmaceuticals PLC for the Middle
East and certain countries in North Africa. Aeterna Zentaris holds rights
for the rest of the world.
About Aeterna Zentaris
Aeterna Zentaris is an oncology and endocrinology drug
development company currently investigating treatments for various
unmet medical needs. The Company's pipeline encompasses compounds
at all stages of development, from drug discovery through to
marketed products. For more information please visit
www.aezsinc.com.
Forward-Looking Statements
This press release contains forward-looking statements made
pursuant to the safe harbour provisions of the U.S. Securities
Litigation Reform Act of 1995. Forward-looking statements involve
known and unknown risks and uncertainties that 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 risk that safety and efficacy data from any of our
Phase 3 trials may not coincide with the data analyses from
previously reported Phase 1 and/or Phase 2 clinical trials, 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 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, unless
required to do so by a governmental authority or by applicable
law.
SOURCE AETERNA ZENTARIS INC.