AEterna Zentaris Presents Detailed Phase 1 Results for Anti-Cancer Compound AEZS-108 at ASCO Meeting
June 04 2007 - 8:30AM
PR Newswire (US)
AEZS-108 was well tolerated and anti-tumor activity was observed in
7 out of 13 patients treated with the highest dose levels QUEBEC
CITY, QC, June 4 /PRNewswire-FirstCall/ -- AEterna Zentaris Inc.
(TSX: AEZ; Nasdaq: AEZS), a global biopharmaceutical company
focused on endocrine therapy and oncology, today announced that it
presented a poster outlining detailed Phase 1 results for its
targeted cytotoxic luteinizing hormone-releasing hormone (LHRH)
analog, AEZS-108 (formerly named AN-152 and ZEN-008), in female
patients with cancers expressing LHRH receptors. Evidence of
anti-tumor activity was found at 160 mg/m(2) or 267 mg/m(2) doses
of AEZS-108, where 7 of 13 patients showed signs of tumor response,
including 3 patients with complete or partial responses. The poster
#3571 titled, "Phase 1 study of ZEN-008 (AN-152), a targeted
cytotoxic LHRH analog, in female patients with cancers expressing
LHRH receptors": G. Emons, M. Kaufmann, A. Gunthert, C. Grundker,
S. Loibl, V.I. Tzekova, M.T. Velikova, S. Tomov, H. Sindermann, J.
Engel and A.V. Schally, was presented Sunday, June 3, 2007 at the
American Society of Clinical Oncology's (ASCO) Annual Meeting
currently being held in Chicago, Illinois. David J. Mazzo, Ph.D.,
President and CEO of AEterna Zentaris commented, "The outcome of
this study with AEZS-108 is very encouraging as we are preparing to
initiate our Phase 2 trial in endometrial and ovarian cancers. We
believe that our targeted approach, including only patients with
LHRH receptor expressing tumors, is the key to both individual
patient safety and clinical benefit as well as the potential
success of the upcoming trial." Details This open, multi-center,
sequential group, dose-escalation Phase 1 study assessed
dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and
pharmacokinetics (PK) of AEZS-108 given once every three weeks in
female patients with cancers expressing LHRH receptors. Safety
monitoring included secretory function of the pituitary gland and
cardiac function, while adverse events were calculated according to
the NCI Common Terminology Criteria for Adverse Events (CTCAE).
Tumor response was evaluated according to Response Evaluation
Criteria In Solid Tumors (RECIST) and by measuring tumor marker
levels (CA125). High performance liquid chromatography (HPLC) with
fluorescence detection was used for plasma PK of AEZS-108 and free
doxorubicin. Seventeen patients with LHRH receptor-positive
ovarian, endometrial or breast cancers were recruited. AEZS-108 was
administered by intravenous infusion over two hours at dosages of
10, 20, 40, 80, 160 and 267 mg/m(2). At 160 mg/m(2), six patients
had a total of 32 cycles and at 267 mg/m(2), seven patients had a
total of 27 cycles. Most of the patients had been pretreated with
various chemotherapies. Results Leucopenia/neutropenia of CTCAE
Grade 4 was dose limiting in two of seven patients at 267 mg/m(2).
The patients recovered spontaneously from hematoxicity without use
of hematopoietic growth factors. The most frequently observed
non-hematological toxicities were alopecia, nausea and fatigue.
Most toxicities were of Grade I. Two patients at the dose levels of
160 and 267 mg/m(2) had a moderate allergic skin reaction (CTCAE
Grade 2) during the first infusion; subsequent cycles with
anti-allergic pre-medication were tolerated. No indication of
cardiac toxicity or impairment of the pituitary gland function was
reported. Regarding tumor response, at 160 mg/m(2), one patient
with ovarian cancer showed the complete disappearance of a
malignant lymph node (diameter 17 mm) at the first follow-up and
received a total of six treatment cycles. Another patient showed
stable disease for six cycles and one patient had stable disease
until cycle 5. At 267 mg/m(2) one patient with ovarian cancer had a
partial response of liver metastasis which was accompanied by a
complete normalization of CA125 levels. Additionally, one patient
showed complete CA125 tumor marker response (no evaluable target
lesions in this patient) and received six treatment cycles.
Finally, two patients showed stabilization of disease under
treatment with 267 mg/m(2) of AEZS-108 and were treated with five
and six treatment cycles, respectively. In one of these patients,
an additional transient minor tumor regression was observed. PK
analyses showed dose-dependent plasma levels of AEZS-108 and only
minor (10-30%) release of doxorubicin. Conclusions - AEZS-108 was
well tolerated by patients with gynecological tumors; - AEZS-108 is
the first drug in a clinical study that targets the cytotoxic
activity of doxorubicin specifically to LHRH-receptor expressing
tumors; - Signs of anti-tumor activity were observed in 7 out of 13
patients treated with 160 or 267 mg/m(2) of AEZS-108, including 3
patients with complete or partial response; and - Recommended dose
for further clinical studies will be 267 mg/m(2) given once every
three weeks. Based on the Phase 1 results, the Company plans to
initiate a Phase 2 trial with AEZS-108 in patients with
LHRH-receptor expressing gynecological tumors (advanced or
recurrent ovarian and endometrial tumors) before year end. About
Cytotoxic Conjugate AEZS-108 AEZS-108 is a targeted cytotoxic
peptide conjugate which is a hybrid molecule composed of a
synthetic peptide carrier and a well-known cytotoxic agent,
doxorubicin. The design of this product allows for the specific
binding and selective uptake of the cytotoxic conjugate by the LHRH
receptor-positive tumors. The binding of conjugate molecule
AEZS-108 to cancerous cells that express these receptors results in
its accumulation in the malignant tissue. This binding is followed
by internalization and retention of the cytotoxic drug,
doxorubicin, in the cells. Therefore, since they target specific
cells, cytotoxic conjugates are postulated to be less toxic, have
less side-effects and are more effective in vivo than the
respective non-conjugated/non-linked cytotoxic agents in inhibiting
tumor growth. 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 http://www.aeternazentaris.com/ Forward-Looking
Statements This press release contains forward-looking statements
made pursuant to the safe harbor provisions of the U.S. Securities
Litigation Reform Act of 1995. Statements that are not historical
facts, including statements preceded by, followed by, or that
include the words "believes", "anticipates", "intends", "plans",
"expects", "estimates", "will," "may", "should", "approximately",
and the negative or other variations of those terms or comparable
terminology, are forward-looking statements. Such statements
reflect management's current views, intentions, strategies and
plans and are based on certain assumptions. 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 ability of AEterna
Zentaris to implement its business strategies, the availability of
funds and resources to pursue R&D projects, the successful and
timely completion of clinical studies, the ability of AEterna
Zentaris 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
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on risks and uncertainties relating to the forward-looking
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forward-looking statements. The Company does not undertake to
update these forward-looking statements. DATASOURCE: AETERNA
ZENTARIS INC. CONTACT: Jenene Thomas, Senior Director, Investor
Relations & Corporate Communications, (908) 938-1475, ; Paul
Burroughs, Media Relations, (418) 652-8525, ext. 406,
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