AEterna Zentaris Partner Keryx Reports a Statistically Significant Benefit in Survival from Updated Results of a Randomized, Dou
January 25 2010 - 8:35AM
PR Newswire (US)
Data Reported at the 2010 ASCO GI Cancers Symposium Demonstrate a
Statistically Significant Improvement in Both Time to Tumor
Progression and Overall Survival in the Perifosine + Capecitabine
Arm Versus Placebo + Capecitabine Arm QUEBEC CITY, Jan. 25
/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), presented updated
results yesterday on the clinical activity of perifosine
(KRX-0401), the Company's PI3K/Akt pathway inhibitor for cancer, in
combination with capecitabine (Xeloda(R)) as a treatment for
advanced, metastatic colon cancer. Abstract #447, entitled,
"Randomized Phase II study of perifosine in combination with
capecitabine (P-CAP) versus capecitabine plus placebo (CAP) in
patients with second- or third-line metastatic colon cancer (mCRC):
Updated results", was presented yesterday in a poster during the
2010 American Society of Clinical Oncology (ASCO) Gastrointestinal
Cancers Symposium, held in Orlando, Florida. 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. Study Design In this randomized, double-blind,
placebo-controlled study conducted at 11 centers across the United
States, heavily pre-treated patients with second- or third-line
metastatic colon cancer were randomized to receive capecitabine (a
chemotherapy used in advanced metastatic colon cancer which is
marketed by Roche as Xeloda(R)) at 825 mg/m2 BID (total daily dose
of 1,650 mg/m2) on days 1 - 14 every 21 days plus either perifosine
or placebo at 50 mg daily. The study enrolled a total of 38
patients, 34 of which were third-line or greater. Of the 38
patients enrolled, 35 were evaluable for response (20 patients on
the perifosine + capecitabine arm and 15 patients on the placebo +
capecitabine arm). Three patients on the placebo + capecitabine arm
were not evaluable for response (2 patients were unevaluable due to
toxicity (days 14, 46) and 1 was unevaluable due to a new
malignancy on day 6). All patients in the perifosine + capecitabine
arm were evaluable for response. The patients in the study were
heavily pre-treated, with the arms well-balanced in terms of prior
treatment regimens. The median number of prior treatment regimens
for all 38 patients was two, with prior treatment regimens for the
P-CAP arm versus CAP arm shown in the table below. Notably, all of
the patients (with the exception of one CAP arm patient) had been
treated with FOLFIRI and/or FOLFOX, almost 80% treated with
Avastin(R), and half treated with an EGFR antibody:
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Prior RX P-CAP CAP All Patients (n equals 20) (n equals 18) (n
equals 38)
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FOLFIRI 18 (90%) 16 (89%) 34 (89%)
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FOLFOX 15 (75%) 13 (72%) 28 (74%)
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FOLFIRI & FOLFOX 13 (65%) 12 (67%) 25 (66%)
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Avastin(R) 15 (75%) 15 (83%) 30 (79%)
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EGFR Antibody (1) 9 (45%) 10 (56%) 19 (50%)
-------------------------------------------------------------------------
5-FU Refractory Status 14 (70%) 13 (72%) 27 (71%)
-------------------------------------------------------------------------
Third Line or greater 18 (90%) 16 (89%) 34 (89%)
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(1) Prior treatment with Erbitux(R) and/or Vectibix(R) The primary
endpoint of this study was to measure Time to Progression (TTP).
Overall Response Rate (ORR), defined as Complete Responses (CR) +
Partial Responses (PR) by RECIST, and Overall Survival (OS) were
measured as secondary endpoints. Study Results The P-CAP arm
demonstrated a statistically significant advantage for TTP and OS,
as well as for the percentage of patients achieving Stable Disease
lasting 12 or more weeks (SD) or better, as compared to the CAP
arm. The P-CAP arm demonstrated a greater than 60% improvement in
OS, a more than doubling of median TTP, and almost a doubling of
the percentage of patients achieving SD or better. In addition, the
ORR was 20% (including one CR, and durable responses) in the P-CAP
arm vs 7% in the CAP arm. The updated efficacy results for all
evaluable patients are as follows:
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ORR % greater than or equal to SD CR / PR (min 12 wks) (Duration of
n (%) Group n Response) p equals 0.036
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20% 1 CR (34 mos - ongoing) P-CAP 20 3 PR (21, 19, 11 mos) 15 (75%)
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7% CAP 15 1 PR (7 mos) 6 (40%)
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Median TTP Median OS* Weeks Months Group p equals 0.0012 p equals
0.0136
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P-CAP 28 (95% CI (12-48)) 18 (95% CI (10.8-25.7))
-------------------------------------------------------------------------
CAP 11 (95% CI (9-15.9)) 11 (95% CI (5.3-16.9))
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*Survival is calculated from date of randomization until the date
of death from any cause, whether or not additional therapies were
received after removal from treatment. NOTE: Kaplan-Meier method
used to calculate both TTP and OS. In addition, TTP and Progression
Free Survival (PFS) are identical for all patients in the study. Of
notable interest, and for the first time presented, were data
showing a highly statistically significant benefit in median OS
(more than doubling) and TTP for the subset of patients who were
refractory to a 5-FU (Fluorouracil) chemotherapy-based treatment
regimen. 5-FU is a core component of the standard of care FOLFIRI
and FOLFOX regimens, and capecitabine is a 5-FU pro-drug. These
results are shown below:
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greater than or equal to SD (min 12 wks) 5-FU Ref n (%) Group n (%)
p equals 0.066
-------------------------------------------------------------------------
P-CAP 14 (70%) 1 PR / 8 SD (64%)
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CAP 11 (73%) 0 PR / 3 SD (27%)
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-------------------------------------------------------------------------
Median TTP Median OS Weeks Months Group p equals 0.0004 p equals
0.0088
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P-CAP 18 (95% CI (12-36)) 15.3 (95% CI (8.4-26))
-------------------------------------------------------------------------
CAP 10 (95% CI (6.6-11)) 6.8 (95% CI (4.8-11.7))
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All 38 patients were evaluable for safety. The P-CAP combination
was well-tolerated with Grade 3 and Grade 4 adverse events of
(greater than) 10% incidence for P-CAP arm versus CAP arm as
follows: anemia (15% vs. 0%), fatigue (0% vs. 11%), abdominal pain
(5% vs. 11%) and hand-foot syndrome (30% vs. 0%). Of note,
incidence of Grade 1 and Grade 2 hand-foot syndrome was similar in
both the P-CAP and CAP arms (25% vs. 22%, respectively). Hand-foot
syndrome is a reported adverse event with capecitabine monotherapy.
Patients who remained on treatment longer in the Phase 2 study had
a greater chance to develop hand-foot syndrome as illustrated by a
median time to onset of Grade 3 and Grade 4 hand-foot syndrome in
the P-CAP arm of 19 weeks. Commenting on the data, Dr. Cathy Eng,
Associate Medical Director for Colorectal Cancer at MD Anderson
Cancer Center in Houston, Texas, stated, "This randomized Phase 2
trial demonstrates the very promising activity of perifosine (an
oral AKT pathway inhibitor) for response, PFS, and OS in the care
of previously treated, advanced colorectal cancer. Akt is
downstream from the EGFR receptor and may have a role also in KRAS
mutant tumor types. Preclinical data suggest that the Akt pathway
inhibitors may be of benefit not only with chemotherapy but also in
combination with other biologic agents. Perifosine is definitely
worthy of further analysis and should be pursued in a Phase 3 trial
in this indication." Dr. Paulo Hoff, Professor of Medicine and
Chairman of Medical Oncology at the University of Sao Paulo, Brazil
and the lead investigator for the capecitabine (Xeloda(R)) Phase 3
approval study stated, "The data we see in this study for the
capecitabine alone group is very much in line with expectation and,
therefore, the combination data of perifosine plus capecitabine
appears very compelling. It seems that the inhibition of Akt and
other pathways by perifosine modulates the activity of
capecitabine. What is of particular interest to me is the TTP and
OS data for the 5-FU refractory patients, which holds great promise
and I urge the Company to move forward into Phase 3." Juergen
Engel, Ph.D., President and CEO at AEterna Zentaris stated, "This
is a very positive development to begin the Year 2010. We now have
a lot of options to create value for our shareholders with our
late-stage compounds in oncology, perifosine and AEZS-108, as well
as in endocrinology with AEZS-130, thanks to the successful
collaboration with our partner Keryx and the continuous interest of
dedicated investigators. We now look forward to the further
development of perifosine." A copy of the abstract is available
upon request. 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
146,100 people will be 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 with some
stages of 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. Avastin(R), a VEGF monoclonal antibody inhibitor, is
commonly administered together with FOLFIRI and FOLFOX. Typically,
patients who fail FOLFIRI and/or FOLFOX (+ Avastin(R)) and who are
considered EGFR-positive (non-mutated, wild-type KRAS status),
receive the EGFR monoclonal antibody inhibitors Erbitux(R) or
Vectibix(R). However, patients who continue to progress beyond
these treatments have a poor prognosis. 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 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
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 except if
we are required by a governmental authority or applicable law.
DATASOURCE: AETERNA ZENTARIS INC. CONTACT: Investor Relations:
Dennis Turpin, SVP and CFO, (418) 652-8525, ext. 242, ; Media
Relations: Paul Burroughs, Director of Communications, (418)
652-8525, ext. 406,
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