Keryx Biopharmaceuticals Announces Positive Data from a Randomized, Multi-Center, Placebo-Controlled, Phase 2 Combination Study
June 01 2009 - 8:30AM
PR Newswire (US)
KRX-0401 + Capecitabine More Than Doubles Time to Progression and
Overall Response Rate as well as Extends Overall Survival vs.
Capecitabine + Placebo in Patients with 2nd or 3rd Line Metastatic
Colon Cancer NEW YORK, June 1 /PRNewswire-FirstCall/ -- Keryx
Biopharmaceuticals, Inc. (NASDAQ:KERX) yesterday announced data on
the clinical activity of KRX-0401 (perifosine), the Company's
Akt-inhibitor for cancer, in combination with capecitabine as a
treatment for advanced colon cancer. Abstract #4081, entitled,
"Randomized phase II study of perifosine in combination with
capecitabine versus capecitabine alone in patients with second- or
third-line metastatic colon cancer," was presented yesterday in a
poster during the Gastrointestinal Cancer -- Colorectal session at
the 45th Annual Meeting of the American Society of Clinical
Oncology (ASCO), taking place in Orlando, Florida. In this
randomized, double-blind, placebo-controlled study conducted at 11
centers across the United States, patients with 2nd or 3rd line
metastatic colon cancer were randomized to receive capecitabine
(Xeloda(R)), an approved drug for metastatic colon cancer, at a
dose of 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.
Treatment was continued until progression. The study enrolled a
total of 38 patients, of which 35 patients were evaluable for
response (20 patients on the capecitabine + perifosine arm and 15
patients on the capecitabine + placebo arm). The three patients not
evaluable for response were all in the capecitabine + placebo arm;
2 patients were inevaluable due to toxicity (days 14, 46) and 1
patient was inevaluable due to a new malignancy on day 6. The
median prior treatment regimens was two, with prior treatment
regimens as follows: 91% of the patients received prior FOLFIRI
(Irinotecan + 5FU + Leucovorin); 74% prior FOLFOX (Oxaliplatin +
5FU + Leucovorin); 63% were previously treated with both FOLFIRI
and FOLFOX; 77% received prior Avastin(R); and 43% prior
Erbitux(R). Prior treatment with single agent capecitabine was
excluded. The primary endpoints of this study were to measure 1)
Time to Progression (TTP); 2) Overall Response Rate (ORR), defined
as the percentage of patients achieving a Complete Response (CR) or
Partial Response (PR) by RECIST, and 3) Clinical Benefit Rate (CBR)
defined as the percentage of patients on treatment for greater than
three months with at least stable disease. Safety of perifosine +
capecitabine vs. capecitabine + placebo in this patient population
was evaluated as a secondary endpoint. Perifosine in combination
with capecitabine was well tolerated with hand/foot syndrome (14%)
and anemia (11%) as the highest reported grade 3/4 adverse events.
Best response and median time to progression of capecitabine +
perifosine vs. capecitabine + placebo were as follows: Group SD
> 12 N CR PR ORR Wks CBR Median TTP N(%) N(%) N(%) N(%) N(%)
(wks) Capecitabine 20 1 3 4 11 15 28.9 weeks + Perifosine (5%)
(15%) (20%) (55%) (75%) {95% CI (13, 48.1)} Capecitabine + Placebo
15 0 1 1 5 6 11 weeks (7%) (7%) (33%) (40%) {95% CI (9, 15.9)}
Perifosine + capecitabine more than doubled time to progression vs.
capecitabine + placebo with a statistically significant p-value =
0.0006. In addition, perifosine + capecitabine more than doubled
the ORR and almost doubled the Clinical Benefit Rate vs.
capecitabine + placebo. Although not a primary endpoint in the
study, overall survival was analyzed with results as follows: Group
Median Overall Survival* % change (months) Capecitabine +
Perifosine 22 {95% CI (12.1, NR)} 26% Increase** Capecitabine +
Placebo 16.3 {95% CI (5.3, 17.1)} * Survival calculated from date
of randomization until date of death from any cause, whether or not
additional therapies were received after removal from treatment **
As of May 2009, median overall survival in the perifosine +
capecitabine patient group is ongoing with 10 of the 20 patients in
this arm still alive. Dr. Howard Burris, Chief Medical Officer and
Director of Drug Development for the Sarah Cannon Research
Institute, Nashville TN, an investigator involved in the
Keryx-sponsored perifosine clinical program since 2004, remarked,
"The results demonstrate that the addition of perifosine to
capecitabine more than doubled time to progression and response
rates, along with extending survival vs. capecitabine alone.
Although not a large sample size, the data here is very interesting
and next steps should be considered." Ron Bentsur, Chief Executive
Officer of Keryx, commented, "Patients with advanced metastatic
colon cancer, who fail standard first and second line treatment,
are truly in need of additional therapies. We are excited about the
data as the combination of perifosine and capecitabine, two oral
agents, appears to demonstrate superior clinical benefit over
capecitabine alone in this advanced patient population. We will now
explore plans to move this program forward in patients with
advanced colorectal cancer." Mr. Bentsur added, "We wish to thank
all the study investigators for their dedication to this clinical
trial." A copy of abstract #4081 is currently available and can be
viewed on-line through the ASCO website: http://www.asco.org/. A
copy of the poster may be obtained by contacting the Company.
KRX-0401 (perifosine) is in-licensed by Keryx from Aeterna
Zentaris, Inc. (Nasdaq: AEZS; TSX: AEZ) in the United States,
Canada and Mexico. About Colon Cancer According to the American
Cancer Society, not counting skin cancers, colorectal cancer is the
third most common cancer diagnosed in the United States. It is
estimated that 106,100 people will be diagnosed with colon cancer,
40,870 people will be diagnosed with rectal cancer and
approximately 50,000 deaths will be attributable to some form of
colorectal cancer in 2009. Surgery is often the main treatment for
early stage colon cancer. When colon cancer metastasizes (spreads
to other parts of the body such as the liver) chemotherapy is
commonly used. Treatment of patients with recurrent or advanced
colon cancer depends on the location of the disease. Chemotherapy
regimens (i.e. FOLFOX or FOLFIRI either with or without
bevacizumab) have shown to increase survival rates for some stages
of colorectal cancer. Currently, there are seven approved drugs for
patients with metastatic colorectal cancer: 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. About Keryx Biopharmaceuticals, Inc. Keryx
Biopharmaceuticals is focused on the acquisition, development and
commercialization of medically important, novel pharmaceutical
products for the treatment of life-threatening diseases, including
renal disease and cancer. Keryx is developing Zerenex(TM)(ferric
citrate), an oral, iron-based compound that has the capacity to
bind to phosphate and form non-absorbable complexes. Zerenex has
recently completed a Phase 2 clinical program as a treatment for
hyperphosphatemia (elevated phosphate levels) in patients with
end-stage renal disease. The Company is also developing KRX-0401
(perifosine), a novel, potentially first-in-class, oral anti-cancer
agent that modulates Akt, a protein in the body associated with
tumor survival and growth. KRX-0401 also modulates a number of
other key signal transduction pathways, including the JNK and MAPK
pathways, which are pathways associated with programmed cell death,
cell growth, cell differentiation and cell survival. KRX-0401 is
currently in Phase 2 clinical development for multiple tumor types.
The Company also actively engages in business development
activities that include seeking strategic relationships for its
product candidates and for the Company, as well as evaluating
compounds and companies for in-licensing or acquisition. Keryx is
headquartered in New York City. Cautionary Statement Some of the
statements included in this press release, particularly those
anticipating future clinical and business prospects for KRX-0401,
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; 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 and in the
American Society of Clinical Oncology's 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 of Keryx Biopharmaceuticals,
Inc., +1-212-531-5962, Web Site: http://www.keryx.com/
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