QUEBEC CITY, June 8 /CNW Telbec/ - AEterna Zentaris Inc. (NASDAQ: AEZS,
TSX: AEZ), a global biopharmaceutical company focused on endocrine therapy and
oncology, today disclosed preliminary results for the Company's European
multi-center Phase 2 trial in non-small cell lung cancer (NSCLC) with its
novel, first-in-class, oral signal transduction inhibitor compound,
perifosine. In 177 patients receiving radiotherapy for inoperable NSCLC, this
randomized, double-blind, placebo-controlled trial assessed the radioenhancing
activity and safety of perifosine co-administration.
About the Phase 2 Trial
Starting one week before the onset of a 4-week course of radiotherapy (51
Gy in 17 fractions), patients with non-metastatic but inoperable NSCLC, mainly
Stage III, received a 5-week course of 150 mg perifosine daily or placebo.
After end of radiotherapy, patients were followed up to determine the time to
tumor recurrence or progression in the area that had been irradiated, the so
called "local control". The primary endpoint of this trial was the extent and
duration of local control, specifically the proportion of patients with
absence of recurrence or progression 12 months after the end of treatment. The
study was planned under the basic assumption that radiotherapy alone would
result in a 35% local control rate, one year after end of therapy in the
placebo group. It was hypothesized that the addition of perifosine would
sensitize tumor cells to the tumor-killing effect of the radiotherapy, leading
to a 15% higher rate of local control. Secondary efficacy parameters included
the times to loco-regional or distant/systemic failure, the tumor response
rate, and overall survival. Safety investigations included the monitoring of
clinical laboratory, electrocardiograms, lung function, and adverse events.
The trial was conducted in collaboration with the Netherlands Cancer
Institute. The lead investigator was Marcel Verheij, MD, Ph.D., Head of the
Department of Radiation Oncology and group leader at the Division of Cell
Biology of The Netherlands Cancer Institute in Amsterdam. In all, 22 study
sites in The Netherlands, Bulgaria, Romania, Macedonia, and Belarus
participated in this trial.
A total of 177 patients were randomized and treated, of whom only 26
reached the milestone of one year post-treatment follow-up without disease
relapse or progression, 14 of 95 patients (14.7%) in the perifosine and 12 of
82 patients (14.6%) in the placebo control group. No difference between
treatment groups could be shown for local, loco-regional and overall disease
control. Also the tumor response rate, as assessed after the end of the
radiotherapy, was not different between the groups.
In contrast to the lack of an observed local effect, patients in the
perifosine group, particularly the subgroup of patients who entered the study
without prior chemotherapy, showed a trend towards longer survival than
patients of the placebo control group despite the short duration of treatment
(5-week course of 150 mg perifosine daily).
There were no safety signals that would lead to an amendment of the
current safety data or risk benefit assessments of perifosine. The type and
severity of side effects were in the expected range.
Marcel Verheij, M.D., Ph.D., lead investigator, "The neutral outcome of
this study is related to the unexpectedly high number of distant failures and
premature discontinuations for other reasons, which heavily compromised the
power of the study to show any effect on the local control rate at one year."
Paul Blake, M.D., Senior Vice President and Chief Medical Officer at
AEterna Zentaris,"In light of these neutral results and an unchanged safety
profile, we can concentrate our efforts on the disease targets of both
multiple myeloma and metastatic colon cancer where, unlike the non-small cell
lung cancer study design, perifosine is dosed 50mg or 100mg daily until
progression. Recently, positive Phase 2 data for multiple myeloma and
metastatic colon cancer were presented at ASH and ASCO meeting, respectively."
Perifosine is a novel, first-in-class, oral anti-cancer agent that
modulates several key signal transduction pathways, including Akt, MAPK, and
JNK that have been shown to be critical for the survival of cancer cells.
Perifosine has demonstrated single agent anti-tumor activity in Phase 1 and
Phase 2 studies and is currently being studied as a single agent and in
combination with several forms of anti-cancer treatments for various forms of
cancer. Most recently, positive results were reported for the single agent use
of perifosine in patients with advanced metastatic renal cancer and in
combination with capecitabine for advanced metastatic colon cancer
(placebo-controlled), as well as for perifosine in combination with bortezomib
+/- dexamethasone in relapsed and refractory myeloma.
About AEterna Zentaris Inc.
AEterna Zentaris Inc. is a global biopharmaceutical company focused on
endocrine therapy and oncology, with proven expertise in drug discovery,
development and commercialization. News releases and additional information
are available at www.aezsinc.com.
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, and 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 requested to
do so by a governmental authority or applicable law.
For further information:
For further information: Investor Relations: Ginette Vallières, Investor
Relations Coordinator, (418) 652-8525 ext. 265, email@example.com; Media
Relations: Paul Burroughs, Director of Communications, (418) 652-8525 ext.