AEterna Zentaris Reports Positive Results from ongoing Phase 1 Trial with AN-152 in Patients with Gynaecological and Breast Can
June 05 2006 - 8:00AM
PR Newswire (US)
Data published at the annual ASCO meeting in Atlanta QUEBEC CITY,
Canada, June 5 /PRNewswire-FirstCall/ -- AEterna Zentaris Inc.
(TSX: AEZ; NASDAQ: AEZS) today disclosed positive Phase 1 results
for its cytotoxic conjugate AN-152 in patients with gynaecological
and breast cancers which showed that the compound has a good safety
profile and no dose-limiting toxicities. Results were part of an
abstract entitled, "Phase I study of AN- 152, a targeted cytotoxic
LHRH analog, in female patients with cancers expressing LHRH
receptors(x)", published at the 42nd Annual Meeting of the American
Society of Clinical Oncology (ASCO), currently being held in
Atlanta, Georgia. Dr. Jurgen Engel, Executive Vice President,
Global R&D and Chief Operating Officer at AEterna Zentaris,
stated, "The pharmacokinetic results provide proof of concept that
the chemical linkage of doxorubicin and the luteinizing hormone
releasing hormone (LHRH) part of the drug molecule is stable in
human blood. This is a prerequisite for the hormone receptor-
mediated, specific uptake of the cytotoxic doxorubicin molecule
into the targeted tumor cells and at the same time, the
minimization of undesired toxic effects to other tissues." Gilles
Gagnon, President and Chief Executive Officer at AEterna Zentaris
added, "We are very pleased and encouraged with the Phase 1 results
for AN- 152. We believe our targeted approach, using patients
specifically expressing LHRH receptors, increases our chances of
success in these indications. This approach is an additional
example of personalized therapy which is becoming more and more the
way of the future. We remain committed to aggressively advancing
our pipeline and providing novel treatments to those suffering from
various types of cancer." Results Eight patients entered the study
and received AN-152 by intravenous infusion over two hours at
dosages of 10, 20, 40, 80, 160, and 267 mg/m(2). Observation of a
grade 2 leukocytopenia in a patient at 160 mg/m(2) led to the
addition of three other patients at this dose level. Patients
received at least two treatment courses, 21 days apart, and went
off study with progressive disease. However, one of the three
patients at the dose level of 160 mg/m(2) with a diagnosis of
ovarian cancer, showed stabilization of disease and received four
treatment courses. Infusion of AN-152 was well tolerated at all
dosages, without supportive treatment. Pharmacokinetic (PK)
analyses showed dose-dependent plasma levels of AN-152 and only
minor (10%- 20%) release of doxorubicin. Conclusions Infusion of
AN-152 is well tolerated in female patients. No dose-limiting
toxicities were seen up to 267 mg/m(2), which is equimolar to a
doxorubicin dose of 77 mg/m(2). Recruitment at this dose level is
ongoing. The cytotoxic LHRH analog is stable in human plasma, a
prerequisite for receptor-mediated uptake by tumor tissue.
Stabilization of disease was observed in one of eight patients in
the ongoing Phase 1 study. Background Human breast, endometrial and
ovarian cancers commonly express receptors for luteinizing hormone
releasing hormone (LHRH-R). 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 I 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. (x)Author Block: G. Emons, M. Kaufmann, A. R. Gunthert, M.
Hamid-Werner, C. Grundker, S. Loibl, A. V. Schally; George August
University, Goettingen, Germany; J.W. Goethe University, Frankfurt,
Germany; V.A. Hospitals, New Orleans / Miami, LA 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 internalisation 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. AN-152 is currently in a Phase
I trial in breast, endometrial and ovarian cancers. About AEterna
Zentaris Inc. AEterna Zentaris Inc. is a growing global
biopharmaceutical company focused on oncology and endocrine therapy
with proven expertise in drug discovery, development and
commercialization. AEterna Zentaris also owns 48.29% of the equity
of Atrium Biotechnologies Inc. (TSX: ATB.sv) and 64.7% of its
voting rights. Atrium is a developer, manufacturer and marketer of
science-based products for the cosmetics, pharmaceutical, chemical
and nutritional industries. 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. (FORMERLY/ANCIENNEMENT - LES LABORATOIRES AETERNA
CONTACT: Media Relations: Paul Burroughs, (418) 652-8525 ext. 406,
; Investor Relations: Jenene Thomas, (418) 655-6420, (908)
996-3154,
Copyright