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
*First-line consolidation in patients with diffuse large B-cell
*Treatment of elderly patients with non-Hodgkin’s lymphoma (NHL)
*New drug combinations to treat follicular non-Hodgkin’s lymphoma
*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
*Spectrum is sponsoring or funding important, ongoing clinical studies of
*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. -- December 13, 2012
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
“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
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
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
Abstract # 2758 - Novel Imaging Modalities in Innovative Xenograft Mouse
Models of T-Cell Lymphoma Confirm Marked Synergy of Romidepsin and
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
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
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
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.
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
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.
Co-administration of drugs subject to renal clearance (e.g., probenecid,
NSAIDs, and trimethoprim/sulfamethoxazole) may result in delayed renal
Please see FOLOTYN® Full Prescribing Information at www.FOLOTYN.com.
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
Press spacebar to pause and continue. Press esc to stop.