Keryx Reports Statistically Significant Benefit in Survival from Updated Results of a Randomized, Double-Blind, Placebo-Controll
January 25 2010 - 8:30AM
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 Conference Call to Discuss
Data to be Held on Thursday, January 28th at 9am EST NEW YORK, Jan.
25 /PRNewswire-FirstCall/ -- Keryx Biopharmaceuticals, Inc.
(NASDAQ:KERX) yesterday reported updated results on the clinical
activity of KRX-0401 (perifosine), the Company's PI3K/Akt pathway
inhibitor for cancer, in combination with capecitabine (Xeloda®) 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. 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®) at 825 mg/m2
BID (total daily dose of 1650 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 patients 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®, and half treated
with an EGFR antibody: P-CAP CAP All Patients Prior RX (n=20)
(n=18) (n=38) -------- ------ ------ ------------ FOLFIRI 18 (90%)
16 (89%) 34 (89%) ------- -------- -------- -------- FOLFOX 15
(75%) 13 (72%) 28 (74%) -------- -------- -------- -------- FOLFIRI
& FOLFOX 13 (65%) 12 (67%) 25 (66%) ---------------- --------
-------- -------- Avastin(R) 15 (75%) 15 (83%) 30 (79%) --------
-------- -------- -------- EGFR Antibody (1) 9 (45%) 10 (56%) 19
(50%) ------------- ------- -------- -------- 5-FU Refractory
Status 14 (70%) 13 (72%) 27 (71%) --------------- -------- --------
-------- Third Line or > 18 (90%) 16 (89%) 34 (89%)
--------------- -------- -------- -------- (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 versus
7% in the CAP arm. The updated efficacy results for all evaluable
patients are as follows: ORR % Greater than Median TTP Median OS*
----- ------------ ---------- ---------- CR / PR or equal to Weeks
Months ------- ----------- ----- ------ (Duration of SD (min 12
Group n Response) wks) p=0.0012 p=0.0136 ----- --- -------------
----------- -------- -------- n (%) ----- p=0.036 ------- 28 [95%
CI 18 [95% CI P-CAP 20 20% 15 (75%) (12-48)] (10.8-25.7)] ----- ---
--- -------- ----------- ------------- 1 CR (34 mos - ongoing)
--------------- 3 PR (21, 19, 11 mos) ----------------- 11 [95% CI
11 [95% CI CAP 15 7% 6 (40%) (9-15.9)] (5.3-16.9)] --- --- ---
------- ----------- ----------- 1 PR (7 mos) ------------ *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 a 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: Greater than or Median TTP Median OS
--------------- ---------- --------- 5-FU Ref equal to Weeks Months
-------- -------- ----- ------ Group n (%) SD (min 12 wks) p=0.0004
P=0.0088 ----- ----- --------------- -------- -------- n (%) -----
p=0.066 ------- 18 [95% CI 15.3 [95% CI P-CAP 14 (70%) 1 PR / 8 SD
(64%) (12-36)] (8.4-26)] ----- -------- -----------------
---------- ------------ 10 [95% CI 6.8 [95% CI CAP 11 (73%) 0 PR /
3 SD (27%) (6.6-11)] (4.8-11.7)] --- -------- -----------------
---------- ------------ All 38 patients were evaluable for safety.
The P-CAP combination was well-tolerated with Grade 3 and 4 adverse
events of > 10% incidence for the 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 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 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®)
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." Ron
Bentsur, Chief Executive Officer of Keryx, commented "We are
extremely excited by the data. It has been several years since any
drug candidate has shown a robust advantage across all key efficacy
parameters in such an advanced metastatic colorectal cancer patient
population, especially a highly statistically significant
improvement in survival. While we will need to confirm these
results in a Phase 3 setting, we are excited at the opportunity to
potentially provide a substantial improvement of care to a very
advanced patient population which has failed some of the biggest
blockbuster cancer drugs, such as Avastin® and Erbitux®." Mr.
Bentsur added, "We are eager to finalize the design of a Phase 3
protocol in metastatic colorectal cancer within the next 3 months,
in consultation with the FDA, and to commence the Phase 3 study as
soon as practicable thereafter." On Thursday, January 28, 2010, at
9:00 a.m. EST, Keryx will host a conference call featuring Dr.
Paulo Hoff and Dr. Johanna Bendell, Director, GI Oncology Research
and Assoc. Director, Drug Development Unit, Sarah Cannon Research
Institute, who will discuss the Phase 2 data reported at the 2010
ASCO GI Cancers Symposium. In order to participate in the
conference call, please call 1-888-596-2611 (U.S.), 1-913-312-1432
(outside the U.S.), call-in ID: KERYX. The audio recording of the
conference call will be available for replay at
http://www.keryx.com/, for a period of 15 days after the call. A
copy of the poster is available via request to Keryx. Perifosine is
currently in a Phase 3 trial, under Special Protocol Assessment
(SPA), for the treatment of relapsed/refractory multiple myeloma.
KRX-0401 (perifosine) is in-licensed by Keryx from Aeterna Zentaris
Inc. (Nasdaq: AEZS; TSX: AEZ) in the United States, Canada and
Mexico. 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 with some stages of colorectal cancer.
Currently, there are seven approved drugs for patients with
metastatic colorectal cancer: 5-fluorouracil (5-FU), capecitabine
(Xeloda®), irinotecan (Camptosar®), oxaliplatin (Eloxatin®),
bevacizumab (Avastin®), cetuximab (Erbitux®) , and panitumumab
(Vectibix®). 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®, a VEGF monoclonal antibody inhibitor, is
commonly administered together with FOLFIRI and FOLFOX. Typically,
patients who fail FOLFIRI and/or FOLFOX (+ Avastin) and who are
considered EGFR-positive (non-mutated, wild-type KRAS status),
receive the EGFR monoclonal antibody inhibitors Erbitux® or
Vectibix®. However, patients who continue to progress beyond these
treatments have a poor prognosis. About Keryx Biopharmaceuticals,
Inc.Keryx Biopharmaceuticals is focused on the acquisition,
development and commercialization of medically important
pharmaceutical products for the treatment of life-threatening
diseases, including cancer and renal disease. Keryx is developing
KRX-0401 (perifosine), a novel, potentially first-in-class, oral
anti-cancer agent that inhibits the phosphoinositide 3-kinase
(PI3K)/Akt pathway, a key signaling cascade that has been shown to
induce cell growth and cell transformation. KRX-0401 has
demonstrated both safety and clinical efficacy in several tumor
types, both as a single agent and in combination with novel
therapies. KRX-0401 also modulates a number of other key signal
transduction pathways, including the JNK pathway, which are
pathways associated with programmed cell death, cell growth, cell
differentiation and cell survival. KRX-0401 is currently in a Phase
3 trial, under Special Protocol Assessment (SPA), in multiple
myeloma, and in Phase 2 clinical development for several other
tumor types. Keryx is also developing Zerenex(TM) (ferric citrate),
an oral, iron-based compound that has the capacity to bind to
phosphate and form non-absorbable complexes. The Phase 3 clinical
program of Zerenex in the treatment for hyperphosphatemia (elevated
phosphate levels) in patients with end-stage renal disease is
expected to begin this quarter under an SPA agreement with the FDA.
Keryx is headquartered in New York City. Cautionary StatementSome
of the statements included in this press release, particularly
those anticipating future clinical and business prospects for
KRX-0401 (perifosine), may be forward-looking statements that
involve a number of risks and uncertainties. For those statements,
we claim the protection of the safe harbor for forward-looking
statements contained in the Private Securities Litigation Reform
Act of 1995. Among the factors that could cause our actual results
to differ materially are the following: our ability to successfully
complete clinical trials for KRX-0401; the risk that the data (both
safety and efficacy) from future trials of KRX-0401 will not
coincide with data analyses from previous clinical trials; our
ability to meet anticipated development timelines for KRX-0401 due
to recruitment, clinical trial results, manufacturing capabilities
or other factors; and other risk factors identified from time to
time in our reports filed with the Securities and Exchange
Commission. Any forward-looking statements set forth in this press
release speak only as of the date of this press release. We do not
intend to update any of these forward-looking statements to reflect
events or circumstances that occur after the date hereof. This
press release and prior releases are available at
http://www.keryx.com/. The information in our website is not
incorporated by reference into this press release and is included
as an inactive textual reference only. KERYX CONTACT: Lauren
Fischer Director, Investor Relations Keryx Biopharmaceuticals, Inc.
Tel: 212.531.5962 E-mail: DATASOURCE: Keryx Biopharmaceuticals,
Inc. CONTACT: Lauren Fischer, Director, Investor Relations, Keryx
Biopharmaceuticals, Inc., +1-212-531-5962, Web Site:
http://www.keryx.com/
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