Aeterna Zentaris Announces Results On Its Lead Anticancer Agent Perifosine at American Association for Cancer Research Annual Meeting
QUEBEC CITY, April 4 /PRNewswire/ – Aeterna Zentaris Inc. (NASDAQ: AEZS)
(TSX: AEZ) (the “Company”) today announced that two posters on its
lead anticancer agent, perifosine, were presented at the 102(nd) annual meeting of the American Association for Cancer Research
currently held at the Orange County Convention Center in Orlando,
Entitled, “Antitumor activity of novel Akt inhibitor, perifosine in gastric cell
lines”,Tae Soo Kim, Hyo Song Kim, Bo Ram Kwan, Chan Hee Park, Hei-Cheul Jeung,
Woo Ick Jang, Juergen Engel, Hyun Cheol Chung, Jae Kyung Roh, Sun Young
Rha, (Yonsei Cancer Center, Yonsei University College of Medicine,
Perifosine showed single agent anti-proliferative activity in a variety
of gastric cancer cell lines. In 8/13 cell lines resistant to 5-FU,
perifosine showed a synergistic antiproliferative activity with 5-FU.
In 72% of cell lines, high basal levels of pAkt were detected.
Treatment with perifosine reduced tumor growth in nude mice inoculated
subcutaneously with the YCC 2 gastric cancer cell line. Finally, an MTT
based microarray analysis was performed to identify pharmacogenomic
classifiers for synergy in 5-FU resistant cell lines.
Perifosine demonstrated antitumor activity in several gastric cancer
cell lines. Furthermore, perifosine enhanced the antitumor activity of
5-FU in parts of the cell lines – including 5-FU resistant cell lines.
5-FU is the active metabolite of the prodrug Xeloda, which is approved
for the treatment of advanced gastric cancer in many countries
including Japan and Korea.
Entitled “The Akt inhibitor Perifosine strongly enhances the antitumor and
antivascular activity of CD34+ cells engineered to express
membrane-bound tumor necrosis factor-related apoptosis-inducing ligand
(TRAIL)” , Arianna Giacomini, Silvia L. Locatelli, Marco Righi, Loredana Cleris,
Paolo D. Longoni, Marco Milanesi, Maura Francolini, Michele Magni,
Massimo Di Nicola, Alessandro M. Gianni, Carmelo Carlo-Stella (Medical
Oncology, Fondazione IRCCS Istituto Nazionale Tumori Milano and
University of Milan, Milan, Italy).
Pro-apoptotic TRAIL receptors present on tumor cells are known to
represent a potential pharmaceutical target for cancer treatment.
Perifosine stimulated the expression of pro-apoptotic TRAIL receptors
on the multiple myeloma KMS-11 cell line, substantially reduced the
levels of phosphorylated Akt and significantly enhanced the sensitivity
of these cells for trail induced apoptosis. The same molecular effects
were noted in the non-Hodgkin lymphoma cell line SU-DHL-4V. In this
TRAIL resistant cell line, perifosine treatment substantially enhanced
the cytotoxicity of TRAIL treatment to similar levels observed in the
TRAIL sensitive multiple myeloma cell line.
The synergistic activity was confirmed in NOD/SCID mice xenograft
models, where perifosine induced a down-modulation of Akt expression as
well as TRAIL receptor upregulation in tumor cells and tumor
Perifosine markedly enhanced the antitumor activity of the cellular
TRAIL based treatment and was able to overcome TRAIL resistance both in
vitro and in vivo. The results are in line with other studies
demonstrating the synergistic effects of perifosine with cytotoxic
drugs, including bortezomib and 5-FU.
Juergen Engel, Ph.D. Aeterna Zentaris President and Chief Executive
Officer, commented, “Gastric cancer represents a significant threat
especially in Asia. This preclinical work demonstrates the potential of
perifosine especially in combination with Xeloda for the treatment of
gastric cancer. Moreover, both posters are in line with previous data
and the clinical observations emphasizing the benefit of combining
perifosine with cytotoxic drugs in different oncological indications.”
Perifosine is a novel, oral anticancer treatment that inhibits Akt
activation in the phosphoinositide 3-kinase (PI3K) pathway. The product
works by interfering with membranes of cancer cells thereby inhibiting
Akt signaling which then affects cell death, growth, differentiation
and survival. Perifosine, in combination with chemotherapeutic agents,
is currently being studied for the treatment of multiple myeloma,
colorectal cancer and other cancers, and is the most advanced
anticancer agent of its class. Perifosine, as monotherapy, is being
explored in other indications. The US Food & Drug Administration
(“FDA”) has granted perifosine orphan-drug designation in multiple
myeloma and neuroblastoma, and Fast Track designations in both multiple
myeloma and refractory advanced colorectal cancer. Additionally, an
agreement was reached with the FDA to conduct the Phase 3 trials in
both of these indications under a Special Protocol Assessment.
Perifosine has also been granted orphan medicinal product designation
from the European Medicines Agency (“EMA”) in multiple myeloma.
Furthermore, perifosine has received positive Scientific Advice from
the EMA for both the multiple myeloma and advanced colorectal cancer
programs, with ongoing Phase 3 trials for these indications expected to
be sufficient for registration in Europe. Perifosine rights have been
licensed to Keryx Biopharmaceuticals for North America, Yakult Honsha
for Japan and to Handok for Korea.
About Aeterna Zentaris Inc.
Aeterna Zentaris is a late-stage oncology drug development company
currently investigating potential treatments for various cancers
including colorectal, ovarian, endometrial cancer and multiple myeloma.
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 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.