Phase 1 & 2 Data of Perifosine (KRX-0401) in Patients with Advanced Renal Cell Carcinoma Presented Today at the 25th Annual Chem
November 09 2007 - 9:45AM
PR Newswire (US)
Oral Presentation by Dr. Robert Figlin Highlights Phase 2 Data
Showing 31% Partial Response Rate and a 62% Overall Clinical
Benefit Rate to Perifosine Used as a Single Agent and Phase 1 Data
Showing No Evidence of Increased Toxicity When Combined with
Sorafenib NEW YORK, Nov. 9 /PRNewswire-FirstCall/ -- Keryx
Biopharmaceuticals, Inc. today announced positive phase 1 & 2
data of perifosine (KRX-0401) in patients with advanced renal cell
carcinoma (RCC). In an oral presentation entitled "PERIFOSINE: AN
ORAL, AKT INHIBITOR WITH CLINICAL ACTIVITY IN ADVANCED RENAL CELL
CARCINOMA," Dr. Robert Figlin, Medical Oncology Chair and Professor
of Medicine, City of Hope National Medical Center in Duarte, CA
provided an update on the clinical activity of single agent
perifosine from a phase 2 trial (Protocol 207), and reported on the
safety and efficacy of perifosine in combination with sorafenib
from an ongoing phase I study (Protocol 124). Phase 2 Single Agent
in RCC - Protocol 207 Twenty-four patients with advanced renal cell
carcinoma (RCC) were randomized to either the daily (50 mg or
100mg) or weekly (900mg or 1200mg) dose of perifosine. Patients
with measurable disease who received at least 2 courses of
perifosine and at least one tumor measurement after initiation of
perifosine, were considered evaluable for response using RECIST
criteria. Thirteen were evaluable for response. Four of these (31%)
had a partial response and an additional 4 patients (31%) achieved
long-term stable disease for a 62% overall clinical benefit rate.
Five patients progressed. One of the responding patients had
previously failed to respond to both sorafenib and sunitinib. The
results are as follows: 50 1200 or or 100 mg 900 mg Protocol 207
RCC Update All Patients Daily Weekly Enrolled, all tumor types 416
205 211 Renal Cell Carcinoma 24 12 12 Evaluable for response 13 7 6
Partial responses (RECIST) 4 (Duration 4, 6.5, 9, 12 mo's) 2 2 Time
to Progression > 6 mo's 4 (10, 13, 14, 18+ mo's) 3 1 Times with
'+' meaning patient still stable or responding at time of analysis.
Additional renal patients will be enrolled on this study, including
patients with prior exposure to sorafenib and sunitinib. Keryx also
has two multi-center phase 2 trials underway evaluating perifosine
100 mg as a single agent in pts who have failed a prior TKI
(sunitinib or sorafenib), with one of the studies allowing pts who
have also failed prior mTOR. Data from these phase 2 TKI failure
studies will be presented at upcoming meetings. Phase 1 Combination
Perifosine + Sorafenib - Protocol 124 Eighteen patients with
advanced cancers were enrolled in one of four cohorts. Ten of these
patients had advanced RCC with some patients having received a
prior TKI. No grade 4 toxicities were reported and 1 grade 3
hand/foot syndrome has been seen. The combination has been
generally well tolerated. The phase I will enroll an additional 20
patients to confirm the selected MTD. "The data presented here
today further demonstrates perifosine's promising activity as a
single agent. The combination of perifosine with sorafenib is of
great interest and further exploration with this combination in
patients who fail a prior TKI is warranted," stated Dr. Robert
Figlin, who continued, "We are anxious to further explore the
potential of perifosine, either in comparison to, or in combination
with sorafenib, in patients with advanced RCC." I. Craig Henderson,
MD, President of Keryx Biopharmaceuticals, commented, "Perifosine
is clearly an active drug in the treatment of renal cell cancer.
Now it's time for us to determine how active and to better define
the patient populations that will most benefit from perifosine
treatment, either alone or with other drugs." Based on the
promising data in renal cell carcinoma with perifosine as a single
agent and in combination with sorafenib, Keryx Biopharmaceuticals
plans to launch a phase 2/3 clinical program in the 1st half of
2008. About the Phase 2 Trial Design This company-sponsored,
exploratory trial was designed to evaluate the safety and efficacy
of two schedules of perifosine (KRX-0401) in patients with a
variety of tumor types. From February 2005 to May 2007, 416
patients at over 30 centers across the US were first randomized to
receive either 50 mg of perifosine once daily or 1200 mg on a
weekly dose schedule and later to either 100 mg daily or 900 mg
weekly. Because the daily doses appear to be as effective and
clearly less toxic, enrollment continues with randomization between
50 and 100 mg daily. The protocol was designed to accrue 11
patients in a given tumor type and then expand that cohort to 26
patients if a favorable outcome is seen in at least 1 of the first
11 patients. The responses we have seen in this advanced renal cell
carcinoma cohort did not appear dose-dependent as partial responses
and stable disease were noted in both dose groups. This is
consistent with prior data with perifosine where responses have
been equally distributed between higher and lower dose groups.
About the Phase 1 Trial Design - Perifosine + Sorafenib This
company-sponsored trial was designed to evaluate the safety (Part
1) of perifosine in combination with sorafenib for patients with
advanced cancers. Perifosine is escalated from 50 mg qd to 50 mg
tid while sorafenib is escalated from 400 mg qd to 400 mg bid. From
September 2006 to October 2007, 17 patients at 6 centers across the
US were enrolled into one of the four cohorts. No DLT's were
observed and extra patients were enrolled to confirm the last two
cohorts. The study will move into Part 2 where an additional group
of up to 20 patients will be accrued and treated at the determined
MTD in order to determine a Phase II dose that will allow patients
to remain on-study for at least 12 weeks. The effects of the
combination of perifosine and sorafenib will be evaluated for
response rate and time to progression in both parts of the study.
Toxicity Both, the 50 mg and 100 mg dose have been well tolerated.
The main toxicities are nausea, vomiting, diarrhea, and fatigue. In
a pooled analysis, % of patients on the continuous daily dose of 50
mg or 100 mg with no GI toxicity was as follows: % with NO
Gastrointestinal Toxicity 50 mg Daily 100 mg Daily Adverse Event N
= 141 N = 68 Nausea 57% 63% Vomiting 70% 74% Diarrhea 61% 69%
Perifosine (KRX-0401) Mechanism of Action and Profile Perifosine
has been shown to inhibit or otherwise modify signaling through a
number of different signal transduction pathways including Akt,
MAPK, and JNK. Akt isoforms have been found to be overexpressed in
renal, breast, prostate, and pancreatic cancers. Elevated levels of
pAkt have been correlated with poor prognosis in patients with
gastric, hepatocellular, endometrial, prostate, renal cell and head
and neck cancers, as well as glioblastoma. The majority of tumors
expressing high levels of pAkt were high-grade, advanced stage or
had other features associated with poor prognosis. The effects of
perifosine on Akt are of particular interest because of 1) the
importance of this pathway in the development of most cancers; 2)
the evidence that it is often activated in tumors that are
resistant to other forms of anticancer therapy; and 3) and the
difficulty encountered thus far in the discovery of drugs that will
inhibit this pathway without causing excessive toxicity. To date,
over 1,500 patients have been treated with perifosine in trials
conducted both in the US and Europe. Its safety profile is
distinctly different from that of most cytotoxic agents. It does
not cause myelosuppression (depression of the immune system) or
alopecia (hair loss) like many currently available treatments for
cancer. In phase 1/2 trials it has induced tumor regressions and/or
caused disease stabilization in a variety of tumor types.
Responding patients, including stable disease, have been treated
for months to almost 3 years, on both the daily and weekly
schedule. KRX-0401 (perifosine) is in-licensed by Keryx from
Aeterna Zentaris, Inc. (Nasdaq: AEZS; TSX: AEZ) in the United
States, Canada and Mexico. About Renal Cell Carcinoma In 2007, an
estimated 51,000 new cases of RCC and 13,000 deaths attributable to
RCC are expected in the US. The National Cancer Institute reports a
rising incidence of RCC at a rate of approximately 2% per decade.
The disease occurs predominantly in the seventh and eighth decades
in life, and it affects nearly twice as many men as women. About
Keryx Biopharmaceuticals, Inc. Keryx Biopharmaceuticals, Inc. is
focused on the acquisition, development and commercialization of
medically important, novel pharmaceutical products for the
treatment of life-threatening diseases, including diabetes and
cancer. Keryx's lead compound under development is Sulonex(TM)
(sulodexide oral gelcap), previously referred to as KRX-101, a
first-in-class, oral heparinoid compound for the treatment of
diabetic nephropathy, a life-threatening kidney disease caused by
diabetes. Sulonex is in a pivotal Phase 3 and Phase 4 clinical
program under a Special Protocol Assessment with the Food &
Drug Administration. Additionally, Keryx is developing Zerenex(TM),
an oral, iron- based compound that has the capacity to bind
phosphate and form non-absorbable complexes. Zerenex is currently
in Phase 2 clinical development for the treatment of
hyperphosphatemia (elevated serum phosphorous levels) in patients
with end-stage renal disease. Keryx is also developing
clinical-stage oncology compounds, including KRX-0401, a novel,
first-in-class, oral anti-cancer agent that modulates Akt, a
protein in the body associated with tumor survival and growth, and
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. Keryx also has an active in-licensing and
acquisition program designed to identify and acquire additional
drug candidates. Keryx is headquartered in New York City.
Cautionary Statement Some of the statements included in this press
release, particularly those anticipating future the financial
performance and 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 the Phase 1 and
Phase 2 clinical trials for KRX-0401; we may not be able 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: 212.531.5965 E-mail:
DATASOURCE: Keryx Biopharmaceuticals, Inc. CONTACT: Lauren Fischer,
Director - Investor Relations of Keryx Biopharmaceuticals, Inc.,
+1-212-531-5965, Web site: http://www.keryx.com/
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