Spectrum Pharmaceuticals Highlights Promising ZEVALIN®, FOLOTYN® and Belinostat Clinical Data Presented at the 54th Annual Meeting of the American Society of Hematology
-
Investigator-sponsored studies report findings for ZEVALIN®
(ibritumomab tiuxetan) Injection for intravenous use in diverse
settings and potential new indications:
-
First-line consolidation in patients with diffuse large B-cell
lymphoma (DLBCL)
-
Treatment of elderly patients with non-Hodgkin's lymphoma (NHL)
-
New drug combinations to treat follicular non-Hodgkin's
lymphoma (fNHL)
-
Investigator-sponsored preclinical in vivo research showed
potential synergy of FOLOTYN® (pralatrexate injection), approved for
single therapy of relapsed or refractory peripheral T-cell lymphoma
(PTCL), when administered with a second therapeutic agent.
-
In an investigator-sponsored Phase 1 study, belinostat, a novel
HDAC inhibitor, showed evidence of activity in combination therapy in
patients with relapsed or refractory acute leukemia and other
hard-to-treat cancers.
-
Spectrum is sponsoring or funding important, ongoing clinical
studies of ZEVALIN :
-
Phase 3 ZEST trial for first-line consolidation in DLBCL
-
Phase 3 SPINOZA trial for aggressive lymphoma patients
undergoing autologous stem cell transplantation
HENDERSON, Nev.--(BUSINESS WIRE)--
Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biotechnology company with
fully integrated commercial and drug development operations with a
primary focus in hematology and oncology, today announced promising
clinical data from investigator-sponsored studies of ZEVALIN®
(ibritumomab tiuxetan) Injection for intravenous use, FOLOTYN®
(pralatrexate injection), and belinostat, Spectrum's novel histone
deacetylase (HDAC) inhibitor. As reported in poster presentations at the
recent 54th Annual Meeting of the American Society of Hematology (ASH),
studies of ZEVALIN showed promising results in diverse settings and
potential indications, including first-line consolidation in patients
with diffuse large B-cell lymphoma (DLBCL); treatment of elderly
patients with non-Hodgkin's lymphoma (NHL), and new drug combinations to
treat follicular non-Hodgkin's lymphoma (fNHL). In addition, preclinical in
vivo research showed promising synergistic, anti-tumor activity of
FOLOTYN, while a Phase 1 study demonstrated early evidence of activity
of belinostat in combination therapy of patients, including those with
relapsed or refractory acute leukemia.
"This year's ASH meeting was another important conference for Spectrum,
both because of the number of presentations — 12 for ZEVALIN, 3 for
FOLOTYN and 4 for belinostat — and the high quality of the data," said
Rajesh C. Shrotriya, M.D., Chairman, President and Chief Executive
Officer of Spectrum Pharmaceuticals, Inc. "Members of the Eastern
Cooperative Oncology Group, Sunnybrook Health Sciences Centre in Toronto
and other key institutions around the world have reported findings that
can help expand our understanding of ZEVALIN in specific patient groups,
as well as in potential new applications and in combination with other
therapies. Further, we are pleased with the reports from studies testing
combination regimens that incorporate either FOLOTYN or belinostat,
demonstrating research interest in potential synergies, especially for
hard-to-treat diseases."
Spectrum's R&D program for ZEVALIN includes, among other initiatives,
two Phase 3 studies that are sponsored or funded by the Company: the
Phase 3 ZEST trial for first-line consolidation in patients with newly
diagnosed DLBCL and the investigator-sponsored Phase 3 SPINOZA trial for
patients with aggressive lymphoma who receive autologous stem cell
transplantation (ASCT).
Select ASH Presentation Summaries
Following are summaries of key ZEVALIN, FOLOTYN and belinostat
presentations at ASH:
Abstract # 1978 - Autologous Stem Cell Transplantation with
Yttriumm-90-Ibritumomab Tiuxetan (Zevalin) Plus BEAM Conditioning in
Patients with Refractory Non-Hodgkin Diffuse Large B-Cell Lymphoma:
Results of a Prospective, Multicenter, Phase II Clinical Trial
A multi-center, investigator-sponsored Phase 2 study in Spain evaluated
Zevalin and BEAM chemotherapy (carmustine, etoposide, cytarabine, and
melphalan) prior to ASCT in patients with refractory DLBCL. Patients had
received a median of 3 (range 2-6) therapies prior to transplantation.
Overall response 100 days after transplantation was 70% with 60%
complete responses. After a median follow-up of 22.7 months for alive
patients 2-year overall and progression-free survival was 65% and 63%,
respectively. The authors concluded that "ASCT with conditioning
including Zevalin radioimmunotherapy plus BEAM is safe, and results in a
very high response rate with promising survival in this very poor
prognosis group of refractory DLBCL patients." Prof. Arnon Nagler, Tel
Aviv University Sackler School of Medicine, who did not participate in
the study, commented: "Results of this and other Phase 2 studies affirm
the wisdom to confirm these results, quickly and definitively, in the
recently commenced randomized, international ‘SPINOZA' study."
Abstract # 2687 - A Phase II Trial of R-CHOP Followed by Zevalin
Radioimmunotherapy for Patients with Previously Untreated Stages I and
II CD20+ Diffuse Large Cell Non-Hodgkin's Lymphoma: an Eastern
Cooperative Oncology Group Study (E3402)
Clinical centers within the Eastern Cooperative Oncology Group (ECOG)
conducted a Phase 2 study of ZEVALIN for first-line consolidation in
patients with early, Stage I - II DLBCL who previously achieved a
partial response (PR) or functional complete response (CR or CRu/PR and
PET negative) following R-CHOP chemotherapy (rituximab,
cyclophosphamide, doxorubicin, vincristine, and prednisone). Clinical
findings showed that, for the patients who completed ZEVALIN
consolidation, 87% were in CR/CRu and 89% were in functional CR. At 4
years, 88% of patients remained progression free and 98% were alive.
Abstract # 2742 - RIT with 90Y Ibritumomab Tiuxetan in Patients with
Non-Hodgkin Lymphoma Over 65 Years
An investigator-sponsored Phase 2 study in patients over 65 years of
age, mean age 72.8 years (range 65-87), with CD20+ NHL reported positive
results, demonstrating that consolidation therapy with ZEVALIN early in
the course of treatment resulted in a mean progression free survival
(PFS) of 54.2 months . According to the authors of the clinical trial
abstract, ZEVALIN "offers good and maintained response rate with lower
toxicity in this fragile population." Further, overall survival (OS) in
this population was found to be not inferior to rates that have been
observed in younger NHL patients.
Abstract # 3657 - Short Course of Bendamustine and Rituximab Followed
by 90Y-Ibritumomab Tiuxetan in Patients with Chemotherapy-Naïve
Follicular Lymphoma: Early Results of "Fol-Brite"
Results of an investigator-sponsored Phase 2 study in patients with
grade 1-2 or 3a fNHL showed that of the patients who completed
bendamustine and rituximab conditioning followed by consolidation
treatment with ZEVALIN by the time of a pre-planned interim analysis,
85.7% had achieved a complete response (CR) rate. This CR rate, being
announced for the first time in a major medical conference, well
surpassed the level required to continue the study of this sequential
therapeutic regimen, which the abstract authors noted was "a promising
option for the treatment of follicular lymphoma."
Abstract # 3681 - Sustained Immune Competency and Long Term Molecular
Remissions in FL Patients with FLIPI Risk Factors > 1, Treated Front Line
with R-CHOP Followed by Consolidative 90 Υ-Radioimmunotherapy and
Maintenance Rituximab
Clinicians at Sunnybrook Health Sciences Centre, Toronto, presented
updated findings from a Phase 2 study in patients with high-risk (FLIPI
2-5), advanced-stage fNHL who received "triple therapy" of R-CHOP
induction chemotherapy, followed by ZEVALIN consolidation and 2 years
rituximab maintenance. Of those patients with PCR detectable t(14;18)
translocations who were evaluated before and after Zevalin, 94% became
PCR negative in blood following ZEVALIN consolidation, indicating
Complete Response at the molecular level. For patients with FLIPI=2, 93%
remained progression free over a median follow-up period of 32 months, a
rate similar to or more favorable than previous reports.
Abstract # 2758 - Novel Imaging Modalities in Innovative Xenograft
Mouse Models of T-Cell Lymphoma Confirm Marked Synergy of Romidepsin and
Pralatrexate
Using preclinical, in vivo xenograft tumor models, researchers at
Stanford University and Columbia University demonstrated that FOLOTYN,
when combined with another PTCL-approved therapy (Romidepsin), showed
potential synergistic effects as measured by surface bioluminescence and
ultrasound imaging. Ongoing pharmacokinetic and molecular studies are
seeking to elucidate the mechanistic basis for the potential synergy in
treating patients with PTCL, for whom prognosis still remains poor
despite recent advances.
Abstract # 3588 - Phase I Trial of Belinostat and Bortezomib in
Patients with Relapsed or Refractory Acute Leukemia, Myelodysplastic
Syndrome, or Chronic Myelogenous Leukemia in Blast Crisis - One Year
Update
An investigator-sponsored phase 1 study showed that belinostat, when
administered with a proteasome inhibitor (bortezomib), was
well-tolerated and showed evidence of activity in patients with relapsed
or refractory acute leukemia, myelodysplastic syndrome, or chronic
myelogenous leukemia in blast crisis. No dose-limiting toxicities have
been observed in the study, and no serious adverse events have occurred
at an unexpected frequency or severity. There have been 2 partial
responses and 1 complete response (out of 22 evaluable patients) in the
heavily pretreated population.
About Non-Hodgkin's Lymphoma
According to the National Cancer Institute (www.cancer.gov),
there are expected to be 70,130 new cases of non-Hodgkin's lymphoma
diagnosed and approximately 18,940 deaths in the United States in 2012.
Non-Hodgkin's lymphoma is defined as any of a large group of cancers of
lymphocytes (white blood cells). Non-Hodgkin's lymphomas can occur at
any age and are often marked by lymph nodes that are larger than normal,
fever, and weight loss. There are many different types of non-Hodgkin's
lymphoma. These types can be divided into aggressive (fast-growing) and
indolent or low grade (slow-growing) types, and they can be formed from
either B-cells or T-cells. Prognosis and treatment depend on the stage
and type of disease.
About ZEVALIN® and the ZEVALIN Therapeutic Regimen
ZEVALIN (ibritumomab tiuxetan) injection for intravenous use, is
indicated for the treatment of patients with relapsed or refractory,
low-grade or follicular B-cell non-Hodgkin's lymphoma (NHL). ZEVALIN is
also indicated for the treatment of patients with previously untreated
follicular non-Hodgkin's Lymphoma who achieve a partial or complete
response to first-line chemotherapy.
ZEVALIN is a CD20-directed radiotherapeutic antibody. The ZEVALIN
therapeutic regimen consists of two components: rituximab, and
Yttrium-90 (Y-90) radiolabeled ZEVALIN for therapy. ZEVALIN builds on
the combined effect of a targeted biologic monoclonal antibody augmented
with the therapeutic effects of a beta-emitting radioisotope.
Important ZEVALIN® Safety Information
Deaths have occurred within 24 hours of rituximab infusion, an essential
component of the ZEVALIN therapeutic regimen. These fatalities were
associated with hypoxia, pulmonary infiltrates, acute respiratory
distress syndrome, myocardial infarction, ventricular fibrillation, or
cardiogenic shock. Most (80%) fatalities occurred with the first
rituximab infusion. ZEVALIN administration can result in severe and
prolonged cytopenias in most patients. Severe cutaneous and
mucocutaneous reactions, some fatal, can occur with the ZEVALIN
therapeutic regimen.
Please see full Prescribing Information, including BOXED WARNINGS, for
ZEVALIN and rituximab. Full prescribing information for ZEVALIN can be
found at www.ZEVALIN.com.
About FOLOTYN®
FOLOTYN, (pralatrexate injection), a folate analogue metabolic
inhibitor, was discovered by Memorial Sloan-Kettering Cancer Center, SRI
International and Southern Research Institute and developed by Allos
Therapeutics. In September 2009, the U.S. Food and Drug Administration
(FDA) granted accelerated approval for FOLOTYN for use as a single agent
for the treatment of patients with relapsed or refractory PTCL. This
indication is based on overall response rate. Clinical benefit such as
improvement in progression-free survival or overall survival has not
been demonstrated. FOLOTYN has been available to patients in the U.S.
since October 2009. An updated analysis of data from PROPEL, the pivotal
study of FOLOTYN in patients with relapsed or refractory PTCL, was
published in the March 20, 2011 issue of the Journal of Clinical
Oncology. FOLOTYN has patent protection through July 2022, based on a
five-year patent term extension through the Hatch-Waxman Act. Please see
full Prescribing Information for FOLOTYN at www.FOLOTYN.com.
Important FOLOTYN® Safety Information
Warnings and Precautions
FOLOTYN may suppress bone marrow function, manifested by
thrombocytopenia, neutropenia, and anemia. Monitor blood counts and omit
or modify dose for hematologic toxicities.
Mucositis may occur. If greater-than or equal to Grade 2 mucositis is
observed, omit or modify dose. Patients should be instructed to take
folic acid and receive vitamin B12 to potentially reduce
treatment-related hematological toxicity and mucositis.
Fatal dermatologic reactions may occur. Dermatologic reactions may be
progressive and increase in severity with further treatment. Patients
with dermatologic reactions should be monitored closely, and if severe,
FOLOTYN should be withheld or discontinued. Tumor lysis syndrome may
occur. Monitor patients and treat if needed.
FOLOTYN can cause fetal harm. Women should avoid becoming pregnant while
being treated with FOLOTYN and pregnant women should be informed of the
potential harm to the fetus.
Use caution and monitor patients when administering FOLOTYN to patients
with moderate to severe renal function impairment.
Elevated liver function test abnormalities may occur and require
monitoring. If liver function test abnormalities are greater-than or
equal to Grade 3, omit or modify dose.
Adverse Reactions
The most common adverse reactions were mucositis (70%), thrombocytopenia
(41%), nausea (40%), and fatigue (36%). The most common serious adverse
events are pyrexia, mucositis, sepsis, febrile neutropenia, dehydration,
dyspnea, and thrombocytopenia.
Use in Specific Patient Population
Nursing mothers should be advised to discontinue nursing or the drug,
taking into consideration the importance of the drug to the mother.
Drug Interactions
Co-administration of drugs subject to renal clearance (e.g., probenecid,
NSAIDs, and trimethoprim/sulfamethoxazole) may result in delayed renal
clearance.
Please see FOLOTYN® Full Prescribing Information at www.FOLOTYN.com.
About Belinostat
Belinostat is a Class I and II HDAC inhibitor being studied in multiple
clinical trials as a single agent or in combination with
chemotherapeutic agents for the treatment of various hematological and
solid cancers. Its anticancer effect is thought to be mediated through
multiple mechanisms of action, including the inhibition of cell
proliferation, induction of apoptosis (programmed cell death),
inhibition of angiogenesis, induction of differentiation, and the
resensitization of cells that have become resistant to anticancer agents
such as platinums, taxanes and topoisomerase II inhibitors. Belinostat
is the only HDAC inhibitor in clinical development with multiple
potential routes of administration, including short and continuous
intravenous infusion; and oral administration.
Conducted under a Special Protocol Assessment (SPA) agreement with the
U.S. Food and Drug Administration (FDA), Spectrum's pivotal,
registrational Phase 2 BELIEF trial is evaluating intravenous belinostat
as monotherapy for relapsed or refractory peripheral T-cell lymphoma
(PTCL), an indication for which this drug candidate has been granted
Orphan Drug and Fast Track designations by the FDA. The BELIEF trial is
an open-label, multicenter, single arm efficacy and safety study in
patients with relapsed or refractory PTCL, who have failed at least one
prior systemic therapy. The primary endpoint of the trial is centrally
reviewed objective overall response rate (ORR). The trial included
approximately 100 clinical centers globally, with completion of patient
enrollment announced in September 2011.
About Spectrum Pharmaceuticals, Inc.
Spectrum Pharmaceuticals is a leading biotechnology company focused on
acquiring, developing, and commercializing drug products, with a primary
focus in oncology and hematology. Spectrum and its affiliates market
three oncology drugs — FUSILEV® (levoleucovorin) for
Injection in the U.S.; FOLOTYN® (pralatrexate injection),
also marketed in the U.S.; and ZEVALIN® (ibritumomab
tiuxetan) Injection for intravenous use, for which the Company has
worldwide marketing rights. Spectrum's strong track record in
in-licensing and acquiring differentiated drugs, and expertise in
clinical development have generated a robust, diversified, and growing
pipeline of product candidates in advanced-stage Phase 2 and Phase 3
studies. More information on Spectrum is available at www.sppirx.com.
Forward-looking statement — This press release may contain
forward-looking statements regarding future events and the future
performance of Spectrum Pharmaceuticals that involve risks and
uncertainties that could cause actual results to differ materially.
These statements are based on management's current beliefs and
expectations. These statements include but are not limited to statements
that relate to our business and its future, including certain company
milestones, Spectrum's ability to identify, acquire, develop and
commercialize a broad and diverse pipeline of late-stage clinical and
commercial products, leveraging the expertise of partners and employees
around the world to assist us in the execution of our strategy, and any
statements that relate to the intent, belief, plans or expectations of
Spectrum or its management, or that are not a statement of historical
fact. Risks that could cause actual results to differ include the
possibility that our existing and new drug candidates may not prove safe
or effective, the possibility that our existing and new applications to
the FDA and other regulatory agencies may not receive approval in a
timely manner or at all, the possibility that our existing and new drug
candidates, if approved, may not be more effective, safer or more cost
efficient than competing drugs, the possibility that our efforts to
acquire or in-license and develop additional drug candidates may fail,
our lack of sustained revenue history, our limited marketing experience,
our dependence on third parties for clinical trials, manufacturing,
distribution and quality control and other risks that are described in
further detail in the Company's reports filed with the Securities and
Exchange Commission. We do not plan to update any such forward-looking
statements and expressly disclaim any duty to update the information
contained in this press release except as required by law.
SPECTRUM PHARMACEUTICALS, INC.®, FUSILEV®,
FOLOTYN® and ZEVALIN®,
are registered trademarks of Spectrum Pharmaceuticals, Inc and its
affiliates. REDEFINING CANCER CARE™ and
the Spectrum Pharmaceuticals logos are trademarks owned by Spectrum
Pharmaceuticals, Inc.
© 2012 Spectrum Pharmaceuticals, Inc. All Rights Reserved.
Spectrum Pharmaceuticals, Inc.
Shiv Kapoor, 702-835-6300
Vice
President, Strategic Planning & Investor Relations
InvestorRelations@sppirx.com
Source: Spectrum Pharmaceuticals, Inc.
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