AEterna Zentaris Reports Positive Top Line Phase 1 Results for AN-152 in Patients with Gynaecological and Breast Cancers
November 27 2006 - 7:30AM
PR Newswire (US)
Company to target ovarian and endometrial cancers for Phase 2 trial
QUEBEC CITY, Nov. 27 /PRNewswire-FirstCall/ -- AEterna Zentaris
Inc. (TSX: AEZ; NASDAQ: AEZS) today disclosed additional positive
top line Phase 1 results for its cytotoxic conjugate AN-152 in
patients with gynaecological and breast cancers. Further data
showed the compound's good safety profile and established the
maximum tolerated dose (MTD) at 267 mg/m(2) which will be the
recommended dose for a Phase 2 trial. In addition to good safety
data, the trial provided a hint of efficacy as disease
stabilization and regression of lesions were observed at the 160
mg/m(2) and 267 mg/m(2) dose levels. Dr. Jurgen Engel, Executive
Vice President, Global R&D and Chief Operating Officer at
AEterna Zentaris, stated, "This additional data provides further
proof of concept that the chemical linkage of doxorubicin and the
luteinizing hormone-releasing hormone part of the drug molecule is
stable in human blood. Most importantly, we witnessed a good safety
profile and a hint of efficacy enabling us to establish a suitable
dose for further development of AN-152 in the treatment of various
cancers." Gilles Gagnon, President and Chief Executive Officer at
AEterna Zentaris added, "We are very pleased and now even more
encouraged with the latest Phase 1 results for AN-152 which lend
further credibility to our very promising oncology platform. By
targeting patients suffering from ovarian and endometrial cancer
with confirmed LHRH receptor status, we believe we may increase our
chances of success for our Phase 2 program in these indications.
This targeted approach is an additional example of personalized
therapy which is becoming more and more the way of the future."
About the AN-152 Phase 1 Trial in Gynaecological and Breast Cancers
This ongoing Phase 1 open-label, multi-center, dose-escalation,
safety and pharmacokinetic study conducted in Europe, includes 17
patients suffering from breast, endometrial and ovarian cancers
with proven luteinizing hormone-releasing hormone (LHRH) receptor
status. Patients were administered AN-152 by intravenous infusion
over two hours at dosages of 10, 20, 40, 80, 160 and 267 mg/m(2).
Patients received at least two treatment courses, 21 days apart.
Results Dose escalation was stopped at 267 mg/m(2), which is
equimolar to a doxorubicin dose of 77 mg/m(2), and declared as
maximum tolerated dose (MTD) due to dose-limiting although rapidly
reversible hematoxicity (CTC grade 4 leucocytopenia/neutropenia) in
two out of six patients. Pharmacokinetic (PK) analyses showed
dose-dependent plasma levels of AN-152 and only minor (10%-30%)
release of doxorubicin. One complete response (TBC by forthcoming
CT scan) and two stable disease out of six patients at the 160
mg/m(2) dose level were reported, while at the 267 mg/ m(2) dose
level, one partial response and three stable disease were observed
from this group of seven patients. Conclusion Infusion of AN-152 is
well tolerated in female patients. Disease stabilization and
regression of lesions are promising signals for therapeutic
activity of the cytotoxic LHRH analog, most probably through
receptor-mediated uptake by tumor tissue. Because of the rapid
reversibility of the potentially dose-limiting hematoxicity even in
patients with multiple prior therapies, the dose of 267 mg/m(2) is
going to be recommended for Phase 2 trials with ovarian and
endometrial cancer as targeted indications. Ovarian and endometrial
cancers are two forms of cancer where LHRH receptors are highly
expressed. Background Human breast, endometrial and ovarian cancers
commonly express receptors for luteinizing hormone-releasing
hormone (LHRH-R). High-affinity binding sites for LHRH are found in
52% of human breast cancers, as well as in 80% of human ovarian and
endometrial cancers. LHRH-R can be used for targeted chemotherapy
with AN-152, in which doxorubicin is linked to (D-Lys(6))-LHRH.
Safety pharmacology and toxicity studies in mice, rats and dogs
demonstrated a significantly reduced cardiotoxic potential of
AN-152 compared with doxorubicin, e.g. no QT prolongation,
myocarditis or fibrosis in the appropriate models. The Phase 1
study assessed dose-limiting toxicities (DLTs), maximum tolerated
dose (MTD), and pharmacokinetics (PK) of AN-152 given once every
three weeks in patients with gynaecological and breast cancers.
About Cytotoxic Conjugate AN-152 Targeted cytotoxic peptide
conjugates are hybrid molecules composed of a synthetic peptide
carrier and a well-known cytotoxic product. The design of these
products allows for the specific binding and selective uptake of
the cytotoxic conjugates by the LHRH receptor-positive tumors. The
binding of cytotoxic conjugates to cancerous cells that express
these receptors results in an accumulation of the antiproliferative
agent in the malignant tissue. This binding is followed by
internalization and retention of the cytotoxic drug in the cells.
Therefore, since they target specific cells, cytotoxic conjugates
are much less toxic, have less side-effects and are more effective
in vivo than the respective radicals in inhibiting tumor growth.
About AEterna Zentaris Inc. AEterna Zentaris Inc. is a growing
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. 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 availability of funds and resources to pursue
R&D projects, the successful and timely completion of clinical
studies, 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
the 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. DATASOURCE: AETERNA
ZENTARIS INC. CONTACT: Media Relations : Paul Burroughs, (418)
652-8525 ext. 406, ; Investor Relations : Jenene Thomas, (418)
655-6420 or (908) 996-3154,
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