QUÉBEC CITY, June 3, 2013 /CNW
Telbec/ - Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZ)
(the "Company") today announced that final data for the Phase
1 portion of the ongoing Phase 1/2 trial with its lead oncology
compound, zoptarelin doxorubicin (AEZS-108), demonstrated the
compound's promising anti-tumor activity in heavily pre-treated men
with castration- and taxane-resistant prostate cancer. Results were
presented earlier today by lead investigator, Jacek Pinski, MD, PhD, of the USC Norris Comprehensive Cancer Center, during a
poster session at the American Society of Clinical Oncology's
("ASCO") Annual Meeting in San
Francisco.
David Dodd, President and CEO of
Aeterna Zentaris stated, "We are encouraged with the Phase 1
portion data and look forward to further results from the current
Phase 2 portion of this investigator-driven trial. Because
luteinizing hormone-releasing hormone receptors are expressed in a
great number of prostate cancers, we believe that zoptarelin
doxorubicin (AEZS-108), which specifically targets those receptors,
may represent a novel targeted treatment for men with this disease.
Expansion into prostate, breast and bladder cancer with zoptarelin
doxorubicin (AEZS-108) after positive Phase 2 results in
endometrial and ovarian cancer, is further demonstration of the
potential of this innovative compound in a variety of cancer
indications for both men and women."
Methods
This was a dose-escalation Phase 1 trial in men with castration-
and taxane-resistant prostate cancer to confirm the dose
established in a Phase 1 trial in women. Patients received
zoptarelin doxorubicin (AEZS-108) every 21 days until progression
or unacceptable toxicity. The primary endpoint was safety.
Circulating Tumor Cells ("CTC") were captured with a novel slot
microfilter and identified by PSA and DAPI staining. AEZS-108
internalization was visualized by fluorescence microscopy.
Results
Eighteen men with a median of 2 prior chemotherapy regimens
(range 1-5) and a median PSA of 106.4 ng/mL (range 8.4-1624.0)
were enrolled. The dose of zoptarelin doxorubicin (AEZS-108) was
escalated from 160 mg/m2 to 210 mg/m2 then to
267 mg/m2. There were 2 Dose-Limiting Toxicities ("DLT")
in the 7 patients receiving zoptarelin doxorubicin (AEZS-108) at a
dose of 267 mg/m2 (grade 4 neutropenia and
grade 3 febrile neutropenia), prompting de-escalation to 210
mg/m2, where 1 of 8 patients experienced a DLT (grade 4
neutropenia), establishing 210 mg/m2 as the Maximum
Tolerated Dose ("MTD"). Significant non-hematologic toxicities
included one case of grade 3 nausea. No cardiotoxicity was seen on
serial evaluation and 6 patients completed 6 cycles.
Internalization of zoptarelin doxorubicin (AEZS-108) was
consistently visualized in CTCs 1 to 3 hours after dosing. Maximal
PSA response was stable or decreased in 8 of 18 men.
Conclusion
In general, zoptarelin doxorubicin (AEZS-108) was well tolerated
and demonstrated promising evidence of its anti-tumor activity in
this heavily pretreated population with castration- and
taxane-resistant prostate cancer. Among the 15 evaluable patients
with measurable disease, 10 achieved stable disease and a drop in
PSA was noted in 3 patients. The MTD of zoptarelin doxorubicin
(AEZS-108) in this indication is 210 mg/m2, which is
below the MTD reported in women with refractory endometrial and
ovarian cancer.
The poster entitled, "A Phase I Dose-Escalation Trial of
AEZS-108 in Castration- and Taxane-Resistant Prostate Cancer",
is available on ASCO's website at the following link.
Current Phase 2 Portion of the Study
This is a single-arm Simon Optimum design Phase 2 study of
zoptarelin doxorubicin (AEZS-108) involving up to 37 patients with
pre-treated castration-and taxane-resistant prostate cancer, using
the dose selected (210 mg/m2) in the Phase 1 portion.
The primary endpoint is to evaluate the clinical benefit of
zoptarelin doxorubicin (AEZS-108) for these patients. Clinical
benefit will be defined as non-progression at 12 weeks with no
dose-limiting toxicity or other toxicity requiring termination of
treatment.
More information on the current Phase 2 portion of the trial is
available at this link NCT01240629.
About zoptarelin doxorubicin (AEZS-108)
Zoptarelin doxorubicin (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.
Zoptarelin doxorubicin (AEZS-108) is the first intravenous drug in
advanced clinical development that directs the chemotherapy agent
specifically to Luteinizing Hormone-Releasing Hormone
("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 ovarian
and endometrial cancer and the Company is currently initiating a
Phase 3 trial in endometrial cancer under a Special Protocol
Assessment. Zoptarelin doxorubicin (AEZS-108) is also in Phase 2
trials in triple-negative breast cancer, prostate cancer and
bladder cancer. Zoptarelin doxorubicin (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. Aeterna Zentaris owns worldwide rights to
zoptarelin doxorubicin.
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, 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.