QUÉBEC CITY, Sept. 23, 2011
/PRNewswire/ - Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZ)
(the "Company"), today announced positive interim data for the
Phase 1 portion of its ongoing Phase 1/2 study in castration and
taxane-resistant prostate cancer with its targeted cytotoxic
luteinizing hormone releasing hormone (LHRH) analog, AEZS-108. The
data were presented by Jacek Pinski,
M.D, Associate Professor of Medicine at the Norris Comprehensive
Cancer Center of the University of Southern
California, during a poster session on Saturday, September 24, 2011, at the European
Society of Medical Oncology (ESMO) Congress currently being held in
Stockholm, Sweden. The trial is
being supported by a three year grant of about US$1.5 million from the National Institutes of
Health.
Dr. Pinski stated, "Results for the Phase 1 portion of our
clinical trial exceeded our expectations. In addition to proving to
be very safe, AEZS-108 also demonstrated impressive efficacy even
at low doses."
Juergen Engel, Ph.D., President
and CEO of Aeterna Zentaris commented, "We thank Dr. Pinski and his
colleagues for the exciting outcome of this early study, including
the elegant demonstration of drug internalization in circulating
tumor cells of treated patients. We now look forward to the Phase 2
portion of this study which will have more emphasis on therapeutic
activity. It will also be interesting to see the results from the
correlative studies to further strengthen the rationale of this
personalized treatment approach."
The Phase 1/2 Study
The poster (abstract # 294) entitled, "A Phase I/II Trial of
AEZS-108 in Castration- and Taxane-Resistant Prostate Cancer",
S.V. Liu, A.V. Schally, T. Dorff, S. Groshen, D. Hawes, D.
Quinn, Y.C. Tai, N.L. Block, J. Engel, and J. Pinski, details the
use of AEZS-108, the Company's targeted cytotoxic analog in which
doxorubicin, a well known chemotherapeutic agent is linked to
[D-Lys(6)]-LHRH, in patients with castration-resistant prostate
cancer (CRPC) for which the presence of LHRH receptors has been
confirmed. This is a single arm study with a Phase 1 lead-in 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" model 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
Twelve patients entered the study, 3 patients each received
AEZS-108 at the lower dose levels of 160 and 210 mg/m2,
and 6 patients at 267 mg/m2. Data on 10 patients were
presented; 2 patients were too early for evaluation. AEZS-108 was
generally well tolerated and there were no dose limiting toxicities
so far. The only grade 3 and 4 toxicities were hematologic in
nature. There were no cases of bleeding or infections. To date,
there have been three grade 4 toxicities (2 at 210
mg/m2, 1 at 267 mg/m2), all of which
were asymptomatic. There have been six grade 3 toxicities including
two cases of grade 3 anemia after repeated courses (cycles 5 and 6)
and one case of febrile neutropenia that occurred during cycle
1.
Signs of therapeutic activity included 5 patients with PSA
regression. One of these patients treated at the lowest dose level,
received 8 treatment cycles because he demonstrated continued
clinical benefit. Three out of 4 evaluable patients with radiologic
evaluable disease achieved stable disease per RECIST.
Correlative studies
In correlative studies, the internalization of AEZS-108 was
monitored in circulating tumor cells (CTCs) isolated from treated
patients. CTCs were isolated from patients' blood and uptake of
AEZS-108 was visualized via the autofluoresence of the doxorubicin
moiety. Internalization was demonstrated in CTCs collected 1-3
hours and 24 hours after AEZS-108 infusion. These data demonstrate
for the first time, the internalization of AEZS-108 in tumor cells
of patients, thus, validating the principle of targeted tumor
therapy with AEZS-108 in a clinical setting.
Conclusions
- AEZS-108 was well tolerated at all dose levels
- Early evidence of AEZS-108's anti-tumor activity even at low
dose level
- Drug internalization was demonstrated in captured CTCs
- Phase 2 extension planned after completion of the toxicity
assessment in the final dose level of the Phase 1 portion of the
study.
To consult a copy of the poster, please click here.
About Prostate Cancer
According to the National Cancer Institute (NCI), prostate
cancer is the second most prevalent type of cancer after lung
cancer. The NCI estimates that 240,890 men will be diagnosed with
and 33,720 men will die of prostate cancer in 2011, in the United States alone.
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
1/2 trials in prostate and bladder cancer. A pivotal trial in
endometrial cancer is expected to be initiated by the end of 2011.
AEZS-108 has been granted orphan-drug designation by the FDA and
orphan medicinal product designation from the EMA for the treatment
of ovarian 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.