Aeterna Zentaris Announces Interim Data for its Phase 1/2 Trial with AEZS-108 in Prostate Cancer at ESMO Congress – AEZS-108 well tolerated at all dose levels / Early evidence of anti-tumor activity
QUÃƒ“°BEC 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
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
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.
Twelve patients entered the study, 3 patients each received AEZS-108 at
the lower dose levels of 160 and 210 mg/m(2), and 6 patients at 267 mg/m(2). 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/m(2), 1 at 267 mg/m(2)), 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.
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
-- 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.
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
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.
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.