Keryx Biopharmaceuticals, Inc. Reports Updated Phase 1/2 Data, Including New Survival Data, on KRX-0401 (Perifosine) in the Trea
07 Diciembre 2009 - 7:30AM
PR Newswire (US)
Response Rate Increases to 41% and Median Overall Survival Reported
at 25 Months for All Evaluable Patients NEW YORK, Dec. 7
/PRNewswire-FirstCall/ -- Keryx Biopharmaceuticals, Inc.
(NASDAQ:KERX) today announced updated efficacy and safety data as
well as new survival data on the clinical activity of KRX-0401
(perifosine) in combination with bortezomib (Velcade(R)) (+/-
dexamethasone) in patients with relapsed/refractory multiple
myeloma. Data from the study entitled "A Multicenter Phase 1/2
Study Evaluating the Safety and Efficacy of Perifosine (KRX-0401) +
Bortezomib (Velcade(R)) in Patients with Relapsed or Relapsed /
Refractory Multiple Myeloma Who Were Previously Treated with
Bortezomib," was presented on Saturday, December 5th at the 51st
annual meeting of the American Society of Hematology, in a poster
presentation by Dr. Paul Richardson, Clinical Director of the
Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer
Institute. Dr. Richardson presented updated results from the study
as follows: Trial Results: Eighty-four patients with
relapsed/refractory multiple myeloma were enrolled in a combined
Phase 1/2 study (18 patients in the Phase 1 component and 66
patients in the Phase 2 component). The patients enrolled were
heavily pre-treated with a median of 5 prior lines of therapy
(range 1 - 13), including; -- 100% of patients had been treated
with bortezomib (55% of the patients were previously treated with
at least two bortezomib-based therapies (range 1 - 4) and 81% were
previously treated with bortezomib plus dexamethasone); -- 98% of
patients were previously treated with dexamethasone; -- 94% of
patients were previously treated with lenalidomide (Revlimid(R))
and/or thalidomide (Thalomid(R)); and -- 58% of patients had prior
stem cell transplant. Overall Response Rate (ORR), defined as the
percentage of patients achieving a complete, partial or minor
response (CR, PR or MR), was the primary endpoint, with Time to
Progression (TTP), Progression-Free Survival (PFS), Overall
Survival (OS) and Safety as secondary endpoints. Seventy-three
patients were evaluable for efficacy. Evaluable patients are
defined as those patients who had received at least two cycles of
therapy on the combination of perifosine with bortezomib. Of the 73
evaluable patients, 53 patients (73%) were previously refractory to
bortezomib (defined as progression on or within 60 days of
treatment to a bortezomib-based regimen), including 44 patients who
were refractory to the combination of bortezomib + dexamethasone.
Twenty evaluable patients (27%) were relapsed to a prior
bortezomib-based regimen. Best response for all 73 evaluable
patients was as follows: Evaluable Patients CR /nCR* PR MR ORR SD**
--------- -------- -------- ------- ------- ------- All Evaluable
Patients (n=73) 3 4% 13 18% 14 19% 30 41% 30 41% ------------- ---
--- --- --- --- --- --- --- --- --- Bortezomib Relapsed (n=20) 2
10% 7 35% 4 20% 13 65% 7 35% ---------- --- --- --- --- --- --- ---
--- --- --- Bortezomib Refractory (n=53) 1 2% 6 11% 10 19% 17 32%
23 43% ---------- --- --- --- --- --- --- --- --- --- --- * nCR =
Near Complete Response is defined as meeting the criteria for CR
(non-detectable monoclonal protein by serum and urine), except with
detectable monoclonal protein by immunofixation. ** SD = Stable
Disease for a minimum of 3 months. Approximately 60% (45 / 73) of
patients demonstrated progression (or SD for 4 cycles) at some
point in their treatment and received 20 mg dexamethasone, four
times per week, in addition to perifosine plus bortezomib.
Responses occurred both with patients taking perifosine in
combination with bortezomib and with patients receiving the
combination plus dexamethasone. Best response for each group was as
follows: Best Response CR /nCR PR MR ORR* SD* ------------- -------
-------- ------- ------- ------- Perifosine + Bortezomib (n=73) 2
3% 10 14% 6 8% 18 25% 19 26% ----------------- --- --- --- --- ---
--- --- --- --- --- Dexamethasone added (n=45) 1 2% 6 13% 10 23% 17
38% 14 31% ------------------- --- --- --- --- --- --- --- --- ---
--- * 5 patients achieved an initial response on Perifosine +
Bortezomib alone, and subsequently responded again with the
addition of Dexamethasone. 3 additional patients achieved stable
disease on Perifosine + Bortezomib alone, and subsequently achieved
stable disease again with the addition of Dexamethasone. Reported
for the first time was median Progression-Free Survival (PFS) and
Overall Survival (OS) data for all evaluable patients, as follows:
Evaluable Patients Median PFS* Median OS** ------------------
----------- ----------- 6.4 months 25 months All Evaluable Patients
---------- --------- (n=73) 95% CI (5.3, 7.1) 95% CI (15.5, NR)
---------------------- ----------------- ----------------- NR = Not
Reached * Median PFS and median TTP were identical, as no patient
deaths occurred prior to progression. ** Kaplan Meier methodology
was used to determine overall survival figures. Of particular
interest was the comparison of evaluable patients who were
previously refractory and the patients who were relapsed to a
bortezomib-based regimen. Median PFS and OS for bortezomib relapsed
vs. refractory were as follows: Bortezomib Relapsed vs. Refractory
Median PFS* Median OS** ----------------------- -----------
----------- Not Reached at 38+ Bortezomib Relapsed (n=20) 8.8
months months -------------------------- ----------
------------------ 95% CI (6.3, 11.2) 95% CI (25, NR)
------------------ --------------- Bortezomib Refractory (n=53) 5.7
months 22.5 months ---------- ----------- 95% CI (4.3, 6.4) 95% CI
(12.3, NR) ---------------------------- -----------------
----------------- * Median PFS and median TTP were identical, as no
patient deaths occurred prior to progression. ** Kaplan Meier
methodology was used to determine overall survival figures. No
unexpected adverse events have been observed. Toxicities were
manageable with supportive care. Commenting on the data, Dr. Paul
Richardson stated, "Perifosine continues to demonstrate an
impressive response rate and extended progression-free survival
when combined with bortezomib and dexamethasone in a heavily
pre-treated patient population. The new survival data reported is
particularly encouraging with a median overall survival of more
than 2 years. We look forward to pursuing this combination in the
randomized Phase 3 trial." Dr. Kenneth Anderson, Chief, Division of
Hematologic Neoplasia, Dana-Farber Cancer Institute, added, "The
data presented here further supports the planned Phase 3 trial
design which has been granted Special Protocol Assessment by the
FDA. We are excited to be launching the multi-center trial for this
very promising agent." Ron Bentsur, Chief Executive Officer of
Keryx Biopharmaceuticals, commented, "We wish to thank the
impressive team of multiple myeloma investigators in the Phase 1/2
trial, led by Dr. Richardson and Dr. Anderson. The updated overall
response rate of 41%, an extended PFS, and median overall survival
of 25 months particularly in a patient population where 73% were
previously refractory to bortezomib, is highly encouraging. We look
forward to starting the Phase 3 trial by year-end." Keryx has been
granted a Special Protocol Assessment (SPA) from the FDA for the
Phase 3 study of perifosine in multiple myeloma. Additionally, the
FDA has granted perifosine Orphan Drug and Fast Track designations
in this indication. KRX-0401 (perifosine) is in-licensed by Keryx
from Aeterna Zentaris, Inc. (Nasdaq: AEZS; TSX: AEZ) in the United
States, Canada and Mexico. About KRX-0401 (Perifosine) KRX-0401
(perifosine) is a novel, potentially first-in-class, oral
anti-cancer agent that modulates Akt, and a number of other key
signal transduction pathways, including the JNK pathway, all of
which are pathways associated with programmed cell death, cell
growth, cell differentiation and cell survival. The effects of
perifosine on Akt are of particular interest because of the
importance of this pathway in the development of most cancers, with
evidence that it is often activated in tumors that are resistant to
other forms of anticancer therapy, and the difficulty encountered
thus far in the discovery of drugs that will inhibit this pathway
without causing excessive toxicity. High levels of activated Akt
(pAkt) are seen frequently in many types of cancer and have been
correlated with poor prognosis. About Multiple Myeloma Multiple
myeloma, a cancer of the plasma cell, is an incurable but treatable
disease. Multiple myeloma is the second most-common hematologic
cancer, representing 1% of all cancer diagnoses and 2% of all
cancer deaths. According to the American Cancer Society, in 2009
there will be an estimated 20,580 new cases of multiple myeloma and
an estimated 10,500 deaths from multiple myeloma in the United
States. To date, several FDA approved therapies exist for the
treatment of multiple myeloma. Despite this progress, patients
continue to relapse, become refractory to prior treatments and
eventually die from their disease. Thus, new therapies are needed
to treat these patients and extend their survival. 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 Phase 2 clinical development for multiple tumor types,
with a Phase 3 in multiple myeloma, under Special Protocol
Assessment (SPA), pending commencement by year-end. 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. Zerenex has recently completed a Phase 2
clinical program as a treatment for hyperphosphatemia (elevated
phosphate levels) in patients with end-stage renal disease, and
Keryx is in the process of finalizing the U.S. Phase 3 program for
Zerenex in consultation with the FDA. Keryx is headquartered in New
York City. Cautionary Statement Some of the statements included in
this press release, particularly those anticipating future clinical
trials 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 and cost-effectively complete clinical
trials for KRX-0401; the risk that the data (both safety and
efficacy) from the Phase 3 trial will not coincide with the data
analyses from the Phase 1 / 2 clinical trial previously reported by
the Company; 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 undertake 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 found on our website is not incorporated by reference
into this press release and is included for reference purposes
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, E-mail: Web Site: http://www.keryx.com/
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