AEterna Zentaris Partner, Keryx, Reports Updated Phase 1/2 Data, Including New Survival Data, on Perifosine (KRX-0401) in the Tr
07 Diciembre 2009 - 7:35AM
PR Newswire (US)
Response Rate Increases to 41% and Median Overall Survival Reported
at 25 Months for All Evaluable Patients QUEBEC CITY, Dec. 7
/PRNewswire-FirstCall/ -- AEterna Zentaris Inc. (NASDAQ: AEZS; TSX:
AEZ) (the "Company"), a global biopharmaceutical company focused on
endocrine therapy and oncology, today announced that its partner
Keryx Biopharmaceuticals Inc. ("Keryx") (NASDAQ:KERX) reported
updated efficacy and safety data as well as new survival data on
the clinical activity of perifosine (KRX-0401) 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. Keryx is AEterna Zentaris' partner
and licensee for perifosine in the United States, Canada and
Mexico. Perifosine is also out-licensed to Handok in South Korea
while AEterna Zentaris retains rights for the rest of the world.
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:
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Evaluable Patients CR/nCR* PR MR ORR SD**
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All Evaluable Patients (n=73) 3 4% 13 18% 14 19% 30 41% 30 41%
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Bortezomib Relapsed (n=20) 2 10% 7 35% 4 20% 13 65% 7 35%
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Bortezomib Refractory (n=53) 1 2% 6 11% 10 19% 17 32% 23 43%
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* 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:
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Best Response CR/nCR PR MR ORR SD
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Perifosine + Bortezomib (n=73) 2 3% 10 14% 6 8% 18 25% 19 26%
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Dexamethasone added (n=45) 1 2% 6 13% 10 23% 17 38% 14 31%
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Five patients achieved an initial response on perifosine +
bortezomib alone, and subsequently responded again with the
addition of dexamethasone. Three 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:
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Evaluable Patients Median PFS* Median OS**
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All Evaluable 6.4 months 25 months Patients 95% CI (5.3, 7.1) 95%
CI (15.5, NR) (n=73)
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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:
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Bortezomib Relapsed vs. Refractory Median PFS* Median OS**
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Bortezomib Relapsed 8.8 months Not Reached at (n=20) 95% CI (6.3,
11.2) 38+ months 95% CI (25, NR)
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Bortezomib Refractory 5.7 months 22.5 months (n=53) 95% CI (4.3,
6.4) 95% CI (12.3, NR)
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* 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. "We congratulate our partner Keryx and their principle
investigators Dr. Richardson and Dr. Anderson for the encouraging
results for perifosine in multiple myeloma which further
demonstrate perifosine's potential as a novel treatment for this
indication. We now look forward to the initiation of the Phase 3
study in this same indication, this month", stated Juergen Engel,
Ph.D., President and CEO at AEterna Zentaris. Keryx has been
granted a Special Protocol Assessment (SPA) from the FDA for the
upcoming Phase 3 study of perifosine in multiple myeloma.
Additionally, the FDA has granted perifosine Orphan Drug and Fast
Track designations in this indication. About Perifosine (KRX-0401)
Perifosine is a novel oral anticancer agent that modulates several
key signal transduction pathways, including Akt, MAPK, and JNK that
have been shown to be critical for the survival of cancer cells.
Perifosine has demonstrated both safety and clinical efficacy in
several tumor types, both as a single agent and in combination with
novel therapies. Perifosine 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. Perifosine has also received Orphan Drug
designation from the U.S. Food and Drug Administration (FDA) for
the treatment of multiple myeloma. 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 AEterna
Zentaris Inc. AEterna Zentaris Inc. is a global biopharmaceutical
company focused on endocrine therapy and oncology, with proven
expertise in drug discovery, development and commercialization.
News releases and additional information are available at
http://www.aezsinc.com/. Forward-Looking Statements This press
release contains forward-looking statements made pursuant to the
safe harbor provisions of the U.S. Securities Litigation Reform Act
of 1995. Forward-looking statements involve known and unknown risks
and uncertainties, which could cause the Company's actual results
to differ materially from those in the forward-looking statements.
Such risks and uncertainties include, among others, the
availability of funds and resources to pursue R&D projects, the
successful and timely completion of clinical studies, the ability
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pharmaceutical industry, uncertainties related to the regulatory
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herein to reflect future results, events or developments except if
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DATASOURCE: AETERNA ZENTARIS INC. CONTACT: Investor Relations:
Dennis Turpin, SVP and CFO, (418) 652-8525 ext. 242, ; Media
Relations: Paul Burroughs, Director of Communications, (418)
652-8525 ext. 406,
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