QUÉBEC CITY, Feb. 3, 2012
/PRNewswire/ - Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZ)
(the "Company") today reported positive updated results for the
Phase 1 portion of its ongoing Phase 1/2 study in castration- and
taxane-resistant prostate cancer (CRPC) with AEZS-108 (zoptarelin
doxorubicin), the Company's targeted cytotoxic luteinizing
hormone-releasing hormone (LHRH) analog. Data showed that AEZS-108
was well tolerated and demonstrated early evidence of antitumor
activity in men with CRPC. Data were presented by Jacek Pinski, MD, PhD, Associate Professor of
Medicine at the Norris Comprehensive Cancer Center of the
University of Southern California,
during a poster session at the American Society of Clinical
Oncology Genitourinary Cancers Symposium which is being held in
San Francisco. Prior interim data
on this study were presented at the European Society of Medical
Oncology Congress in September 2011.
The trial is being supported by a three-year US$1.6 million grant from the National Institutes
of Health to Dr. Pinski.
Dr. Pinski stated, "Overall, AEZS-108 has been very well
tolerated in this heavily pre-treated population, though we have
met some hematologic toxicity at the higher dose levels. The
efficacy of this agent, even at lower doses, is impressive and we
are eager to complete the Phase 1 and begin the Phase 2
portion of the study."
Juergen Engel, PhD, President and
CEO of Aeterna Zentaris added, "It is very encouraging to see that
AEZS-108 continues to show good safety and interesting efficacy
data even at this early stage. This compound is a key element of
our personalized medicine approach in oncology, and the dedicated
work of Dr. Pinski and his team ideally fits our commitment to
develop a novel targeted treatment for men suffering from prostate
cancer."
The Phase 1/2 Study
The poster #D3 titled, "A Phase 1 Trial of AEZS-108
in Castration- and Taxane-Resistant Prostate
Cancer", S.V. Liu,
A.V. Schally, T.B. Dorff, D.D.
Tsao-Wei, S.G. Groshen, S.
Xiong, D. Hawes, D.I. Quinn,
Y.C. Tai, N.L. Block, J. Engel, J.
K. Pinski, (NCT01240629), detailed the use of AEZS-108, in
patients with pre-treated CRPC. This is a single-arm study with a
Phase 1 lead-in portion (testing 3 dose levels) to a Phase 2
clinical trial. The primary endpoint of the Phase 1 portion is
safety. The primary objective of the Phase 2 portion is to evaluate
the clinical benefit of AEZS-108 for these patients.
Up to 18 men were planned for the Phase 1 lead-in portion which
follows a "3+3" design to confirm or modify, if needed, the dose
established in a completed Phase 1 trial in women. Patients
received AEZS-108 intravenously over 2 hours every 3 weeks for up
to 6 cycles, until progression of the disease, unacceptable
toxicity or patient withdrawal. Premedication included
dexamethasone 8 mg. Maximal Prostate Specific Antigen (PSA)
response was calculated using PSA Working Group 2 guidelines.
Response Evaluation Criteria in Solid Tumors
(RECIST, v. 1.1) was used to assess response for patients
with measurable disease.
Results
Currently, 13 patients have been treated on 3 dose levels: 3 at
160 mg/m2, 3 at 210 mg/m2, and 7 at
267 mg/m2. Overall, AEZS-108 has been well
tolerated among this group of heavily pre-treated older patients.
To date, there have been 2 dose limiting toxicities; both were
cases of asymptomatic grade 4 neutropenia at the 267
mg/m2 dose level and both patients fully recovered. The
grade 3 and 4 toxicities were primarily hematologic. There has been
minimal non-hematologic toxicity, most frequently fatigue and
alopecia.
Despite the low doses of AEZS-108 in the first cohorts, there is
some evidence of antitumor activity. One patient received 8 cycles
(at 210 mg/m2) due to continued benefit. Among the 5
evaluable patients with measurable disease, 4 achieved stable
disease. At the time of submission, a decrease in PSA was noted in
6 patients. Six of 13 (46%) treated patients have received at least
5 cycles of therapy with no evidence of disease progression at 12
weeks.
Correlative Studies
As part of correlative studies, a feasibility study to capture
circulating tumor cells (CTCs) using a novel microfluidic device
and test for AEZS-108 internalization was also conducted and
feasibility was demonstrated. The autofluorescence of AEZS-108
allows direct visualization of internalization and confirmation of
drug delivery. Complete analysis will explore correlation between
internalization and response.
Conclusions
AEZS-108 is generally well tolerated and has demonstrated early
evidence of antitumor activity in men with CRPC. Correlative
studies on CTCs have demonstrated the uptake of AEZS-108 into the
targeted tumor. After completion of 3 additional patients at 210
mg/m2 dose level, the study will be extended into the
Phase 2 portion.
The poster can be viewed on line through the following link.
About AEZS-108
AEZS-108 represents a new targeting concept in oncology using a
hybrid molecule composed of a synthetic peptide carrier and a
well-known chemotherapy agent, doxorubicin. AEZS-108 is the first
intravenous drug in a clinical study that directs the chemotherapy
agent specifically to LHRH-receptor expressing tumors, resulting in
more targeted treatment with less damage to healthy tissue. The
product has successfully completed Phase 2 studies for the
treatment of endometrial and ovarian cancer, and is also in Phase 2
trials in prostate and bladder cancer. A pivotal trial in
endometrial cancer is expected to be initiated in 2012. AEZS-108
has been granted orphan-drug designation by the FDA and orphan
medicinal product designation from the European Medicines Agency
for the treatment of ovarian cancer. An Investigational New Drug in
the U.S. is in place for the treatment of prostate, bladder and
triple-negative breast cancer. Aeterna Zentaris owns the worldwide
rights to AEZS-108.
About Aeterna Zentaris Inc.
Aeterna Zentaris is a late-stage oncology drug development
company currently investigating potential treatments for various
cancers including colorectal, multiple myeloma, endometrial,
ovarian, prostate and bladder cancer. The Company's innovative
approach of "personalized medicine" means tailoring treatments to a
patient's specific condition and to unmet medical needs. Aeterna
Zentaris' deep pipeline is drawn from its proprietary discovery
unit providing the Company with constant and long-term access to
state-of-the-art therapeutic options. 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.