Keryx Biopharmaceuticals, Inc. Announces Phase 1 and Phase 2 Data on KRX-0401 (Perifosine) in Patients with Relapsed/Refractory
December 10 2007 - 8:21AM
PR Newswire (US)
Dr. Paul Richardson presents Phase 1 results demonstrating clinical
activity of perifosine in combination with bortezomib in patients
previously treated with bortezomib, and provides an update on an
ongoing Phase 2 study of perifosine in combination with
dexamethasone NEW YORK, Dec. 10 /PRNewswire-FirstCall/ -- Keryx
Biopharmaceuticals, Inc. (NASDAQ:KERX) today announced that
positive phase 1 & phase 2 data of perifosine (KRX-0401) in
patients with advanced, relapsed/refractory multiple myeloma (MM)
were presented on Saturday, December 8, 2007 at the 49th Annual
Meeting of the American Society of Hematology. In two separate
poster presentations, Dr. Paul Richardson, Clinical Director of the
Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer
Institute (DFCI) in Boston, MA, provided the phase 1 results on the
clinical activity of perifosine in combination with Bortezomib, and
an update on an ongoing phase 2 study of perifosine in combination
with dexamethasone. Phase 1 Perifosine + VELCADE(R) (Vel) Poster
324-I: A MULTICENTER PHASE 1/2 TRIAL OF PERIFOSINE (KRX-0401) +
BORTEZOMIB IN RELAPSED OR RELAPSED/REFRACTORY MULTIPLE MYELOMA
PATIENTS PREVIOUSLY TREATED WITH BORTEZOMIB: PHASE I RESULTS
Eighteen patients (median age 64 yrs) with advanced MM (83%
relapsed and refractory) were enrolled in one of four cohorts.
Patients had a median of 5 lines of prior therapy and 100% of
patients were previously treated with at least one course of
therapy on bortezomib. Perifosine was escalated from 50 to 100 mg
qd while bortezomib was escalated from 1.0 to 1.3 mg/mm2. No dose-
limiting toxicity and no grade 3 peripheral neuropathy were
reported. Toxicities were generally well managed and tolerated.
Dexamethasone 20mg (day of and day after each Velcade dose) was
added in patients with progressive disease (PD) on perifosine plus
Velcade alone. Sixteen patients on either Velcade plus perifosine
alone or with dexamethasone were evaluable for response, assessed
by modified EBMT/Blade criteria, with results as follows: Relapsed
(Rel) or Response (N = 16)* N (%) Relapsed/Refractory MM Duration
(wks) CR after Peri + Vel 1 (6%) Rel/Refractory 66+ CR after Peri +
Vel + Dex **1 (6%) Rel 36+ PR after Peri + Vel + Dex 1 (6%)
Rel/Refractory 33 MR after Peri + Vel 2 (13%) Rel/ Refractory 31+,
19 MR after Peri + Vel + Dex 4 (25%) Rel/Refractory 46, 36+, 19,
13+ SD after Peri + Vel 3 (19%) Rel/Refractory 39+, 39, 26+ SD
after Peri + Vel + Dex 2 (13%) 1 pt Rel/Ref; other Rel 38, 19 PD
after Peri + Vel 2 (13%) Rel/Refractory 5, 4 Stable disease (SD):
< 25% reduction in M-protein **subject to confirmation *2 pts
were inevaluable for response (removed from study after only 1
cycle of treatment) Times with '+' meaning patient still stable or
responding at time of analysis. In summary, the investigators
conclude that the combination of perifosine and bortezomib (+/-
dexamethasone) was well tolerated and is active in heavily
pre-treated and relapsed/refractory multiple myeloma, including
bortezomib- resistant patients. An overall response rate of 56% (CR
+ PR + MR) was reported with an additional 31% of patients
achieving stable disease (SD). The phase 2 portion of the study is
open with 12 patients enrolled to date with perifosine 50 mg qd +
Velcade 1.3 mg/mm2, D1, 4, 8, 11 every 21 days as the selected
phase 2 dose. Phase 2 Perifosine +/- Dexamethasone (dex) Poster
318-I: MULTI-CENTER PHASE 2 STUDY OF PERIFOSINE (KRX-0401) ALONE
AND IN COMBINATION WITH DEXAMETHASONE (DEX) FOR PATIENTS WITH
RELAPSED OR RELAPSED/REFRACTORY MM: PROMISING ACTIVITY AS
COMBINATION THERAPY WITH MANAGEABLE TOXICITY Sixty-seven highly
pre-treated MM patients (median age 62 yrs) were treated with
perifosine at 150 mg qd to assess the single agent activity in this
patient population. Patients had a median of 4 lines of prior
therapy (range 1 - 11) and 94% of patients were previously treated
with at least one course of dex. If a patient progressed on
perifosine alone, dex (20mg twice weekly) was added to their
perifosine regimen. Toxicity was manageable with no DVT or
peripheral neuropathy reported. Twenty-one patients had perifosine
reduced from 150 to 100 mg qd with no difference in response noted.
In this heavily pre-treated and relapsed/refractory patient
population, perifosine as monotherapy appears to have modest
activity with 33 of 50 evaluable patients (66%) achieving SD. Dex
was added in 39 of 55 pts with progressive disease. Out of 29
patients currently evaluable for response on the combination. an
ORR (CR+PR+MR) of 35% (10/29) was achieved, with an additional 52%
(15/29) of patients achieving SD. Six patients remain on treatment
with duration of response ranging from 15 - 70 weeks. Enrollment
objectives were met and the study is now closed. One additional
clinical poster was presented as follows: Phase 1 Perifosine +
REVLIMID(R) + dexamethasone (dex) Poster 323-I: A MULTIPLE MYELOMA
RESEARCH CONSORTIUM (MMRC) MULTICENTER PHASE I TRIAL OF PERIFOSINE
(KRX-0401) IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE IN
PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA (MM): UPDATED
RESULTS "The data presented further demonstrates perifosine's
promising activity in combination with bortezomib, lenolidomide and
dexamethasone," stated Dr. Richardson, who continued, "we are
especially encouraged by the activity of perifosine combinations in
resistant patients and the favorable toxicity profile seen to date.
We look forward to completing enrollment in both the
perifosine/bortezomib and the perifosine/
lenalidomide/dexamethasone studies in the near future." I. Craig
Henderson, MD, President of Keryx Biopharmaceuticals, commented
"The collaboration between Keryx and groups of multiple myeloma
physicians, often lead by the group from the Dana-Farber Cancer
Institute, and with the involvement of the Multiple Myeloma
Research Consortium (MMRC) has been very rewarding. Together these
studies provide considerable evidence that perifosine has activity
in this disease and suggests possible directions for future
development of the drug." Copies of the posters are available by
request to Keryx Biopharmaceuticals. 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 believed to be distinctly
different from that of most cytotoxic agents. It does not appear to
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 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: KERYX CONTACT:
Lauren Fischer, Director - Investor Relations of Keryx
Biopharmaceuticals, Inc., +1-212-531-5965, Web site:
http://www.keryx.com/
Copyright