AEterna Zentaris Partner Keryx Announces Special Protocol Assessment Agreement with FDA for Phase 3 Trial of Perifosine (KRX-040
03 Febbraio 2010 - 2:35PM
PR Newswire (US)
Phase 3 X-PECT Trial (Xeloda(R) + Perifosine Evaluation in
Colorectal cancer Treatment) to be led by Dr. Johanna Bendell,
Director, GI Oncology Research, Sarah Cannon Research Institute
QUEBEC CITY, Feb. 3 /PRNewswire-FirstCall/ -- AEterna Zentaris Inc.
(Nasdaq: AEZS; TSX: AEZ) (the "Company"), a late-stage drug
development company specialized in oncology and endocrinology,
today announced that its partner, Keryx Biopharmaceuticals
(NASDAQ:KERX), has reached an agreement with the U.S. Food and Drug
Administration (FDA) regarding a Special Protocol Assessment (SPA)
on the design of a Phase 3 trial for its PI3K/Akt pathway
inhibitor, perifosine (KRX-0401), in patients with refractory
metastatic colorectal cancer. The SPA provides agreement that the
Phase 3 study design adequately addresses objectives in support of
a regulatory submission. Keryx is AEterna Zentaris' partner and
licensee for perifosine in the United States, Canada and Mexico.
Perifosine is also out-licensed to Handok in South Korea while
AEterna Zentaris retains rights for the rest of the world. About
the Phase 3 Trial Design The Phase 3 X-PECT (Xeloda(R) + Perifosine
Evaluation in Colorectal cancer Treatment) trial will be a
randomized (1:1), double-blind trial comparing the efficacy and
safety of perifosine + capecitabine (capecitabine is a chemotherapy
marketed by Roche as Xeloda(R)) vs. placebo + capecitabine in
approximately 430 patients with refractory metastatic colorectal
cancer. Patients must have failed available therapy including
5-fluorouracil (5-FU), oxaliplatin (Eloxatin(R)), irinotecan,
bevacizumab (Avastin(R)) and, if K-Ras wild-type (WT), failed
therapy with prior cetuximab (Erbitux(R)) or panitumumab
(Vectibix(R)). For oxaliplatin-based therapy, failure of therapy
will also include patients who discontinued due to toxicity. The
primary endpoint is overall survival (OS), with secondary endpoints
including overall response rate (ORR: complete responses + partial
responses), progression-free survival (PFS) and safety. The median
OS for the X-PECT study's targeted patient population which has
failed prior therapies as described above, is approximately 5
months. The X-PECT study will be powered at 90% to detect a
statistically significant difference in OS, with an assumed median
OS for the control arm of 5-6 months and 7-8 months for the
perifosine arm. Approximately 360 events of death will trigger the
un-blinding of the study. Approximately 40 to 50 U.S. sites will
participate in the study. The study is expected to begin in 2Q
2010, and enrollment is expected to take approximately 12 months,
with study completion expected in 2H 2011. Dr. Johanna Bendell,
Director of GI Oncology Research for the Sarah Cannon Research
Institute, Nashville, Tennessee, will lead the Phase 3
investigational team that includes Dr. Cathy Eng, Associate Medical
Director for the Colorectal Center at MD Anderson Cancer Center in
Houston, Texas. Dr. Johanna Bendell, commented, "More active agents
are needed to improve survival for patients with metastatic
colorectal cancer. We are very excited about this Phase 3 trial,
which is based on the encouraging randomized Phase 2 data that
demonstrated an improvement in overall survival and time to
progression using perifosine plus capecitabine over placebo plus
capecitabine in patients with metastatic colorectal cancer. As
such, we are moving forward with the randomized Phase 3 X-PECT
trial, and we hope to continue to see these improvements in patient
outcomes." Juergen Engel, Ph.D., President and CEO at AEterna
Zentaris stated, "We are very excited about this significant
milestone and would like to reiterate our thanks to our partner
Keryx and the investigators for their valuable collaboration in the
development of perifosine. In 2010, this novel oral anticancer
compound will now be the subject of two Phase 3 registration
trials, and we look forward to its further late-stage development
in other indications in oncology in the coming future." About
Colorectal Cancer According to the American Cancer Society,
colorectal cancer is the third most common form of cancer diagnosed
in the United States. It is estimated that over 146,000 people were
diagnosed with some form of colorectal cancer with over 49,000
patients dying from colorectal cancer in 2009. Surgery is often the
main treatment for early stage colorectal cancer. When colorectal
cancer metastasizes (spreads to other parts of the body such as the
liver) chemotherapy is commonly used. Treatment of patients with
recurrent or advanced colorectal cancer depends on the location of
the disease. Chemotherapy regimens (i.e. FOLFOX or FOLFIRI either
with or without bevacizumab) have been shown to increase survival
rates in patients with metastatic/advanced colorectal cancer.
Currently, there are seven approved drugs for patients with
metastatic colorectal cancer: 5-fluorouracil (5-FU), capecitabine
(Xeloda(R)), irinotecan (Camptosar(R)), oxaliplatin (Eloxatin(R)),
bevacizumab (Avastin(R)), cetuximab (Erbitux(R)), and panitumumab
(Vectibix(R)). Depending on the stage of the cancer, two or more of
these types of treatment may be combined at the same time or used
after one another. For example, FOLFOX combines 5-FU, leucovorin
and oxaliplatin and FOLFIRI combines 5-FU, leucovorin and
irinotecan. Bevacizumab, a VEGF monoclonal antibody, is commonly
administered with chemotherapy. Typically, patients who fail 5-FU,
oxaliplatin, irinotecan, and bevacizumab-containing therapies, and
who have wild-type KRAS status receive EGFR monoclonal antibody
therapy with either cetuximab or panitumumab. Once patients
progress on these agents, there are no further standard treatment
options. About Perifosine (KRX-0401) Perifosine is a novel oral
anticancer agent that modulates several key signal transduction
pathways, including Akt, MAPK, and JNK that have been shown to be
critical for the survival of cancer cells. Perifosine has
demonstrated both safety and clinical efficacy in several tumor
types, both as a single agent and in combination with novel
therapies. Perifosine is currently in a Phase 3 trial, under
Special Protocol Assessment (SPA), in multiple myeloma for which it
has received Orphan Drug and Fast Track designations from the FDA
in this indication. Perifosine is also in Phase 2 clinical trials
for several other tumor types. About Special Protocol Assessments
The Special Protocol Assessment (SPA) process is a procedure by
which the FDA provides official evaluation and written guidance on
the design and size of proposed protocols that are intended to form
the basis for a new drug application. Final marketing approval
depends on the results of efficacy, the adverse event profile and
an evaluation of the benefit/risk of treatment demonstrated in the
Phase 3 trial. The SPA agreement may only be changed through a
written agreement between the sponsor and the FDA, or if the FDA
becomes aware of a substantial scientific issue essential to
product efficacy or safety. For more information on the Special
Protocol Assessment process, please visit:
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Gui
dances/ucm080571.pdf. About AEterna Zentaris Inc. AEterna Zentaris
Inc. is a late-stage drug development company specialized in
oncology and endocrinology. News releases and additional
information are available at http://www.aezsinc.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
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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 except if
we are required by a governmental authority or applicable law.
DATASOURCE: AETERNA ZENTARIS INC. CONTACT: Investor Relations:
Ginette Vallieres, Investor Relations Coordinator, (418) 652-8525,
ext. 265, ; Media Relations, Paul Burroughs, Director of
Communications, (418) 652-8525, ext. 406,
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