FDA Grants Spectrum Pharmaceuticals Accelerated Approval of Beleodaq™ (belinostat) for Injection
Early Action before PDUFA date of August 9, 2014 follows Priority
Beleodaq to be launched through Spectrum's existing sales force
Beleodaq is expected to be available to patients in less than 3
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, announced today that the U.S.
Food and Drug Administration (FDA) has granted Accelerated Approval of
Beleodaq™ for the treatment of patients with relapsed or refractory
peripheral T-cell lymphoma (PTCL). This indication is approved under
accelerated approval based on Tumor Response Rate and Duration of
Response. An improvement in survival or disease-related symptoms
has not been established. Continued approval for this indication may be
contingent upon verification and description of clinical benefit in the
Beleodaq was approved by the FDA on July 3rd, nearly 5
weeks before the PDUFA date (August 9th). This
indication was approved based on data from the multi-center, single-arm
BELIEF trial in 120 evaluable patients, refractory to or who had failed
at least one prior systemic therapy. In this trial, Beleodaq was
associated with hematologic toxicity, infections, hepatotoxicity, tumor
lysis syndrome, gastrointestinal toxicity, and embryo-fetal toxicity.
PTCL comprises a group of rare and aggressive non-Hodgkin's Lymphomas
(NHL) that develop from mature T-cells and accounts for approximately 10
to 15% of all NHL cases in the United States. These patients generally
have a poor prognosis with a low response rate (25-27%) to available
treatment options, and commonly experience repeated treatment failures
until drug resistance or death. Therefore, there has been an important
unmet medical need for these patients with PTCL for additional new
treatment options that are specifically effective for this disease.
"This FDA approval enables us to help address this unmet medical need,
and provide a new treatment option for patients with this
difficult-to-treat and ultimately fatal disease," said Rajesh C.
Shrotriya, MD, Chairman and Chief Executive Officer of Spectrum
Pharmaceuticals. "First with Folotyn® (pralatrexate
injection) and now with Beleodaq, we are very proud to be able to offer
patients and clinicians two approved treatment options for R/R PTCL, and
be a leader in the treatment of T-cell lymphomas. We will be able to
effectively leverage our existing Hematology clinical and sales
infrastructure to expedite the launch of Beleodaq. Now with a total of
five approved Hematology/Oncology drugs and a strong and maturing
development pipeline, Spectrum is well positioned for continued future
"Peripheral T-cell lymphoma (PTCL) is a poor prognosis subtype of
non-Hodgkin's lymphoma with no accepted standard of care," said Owen A.
O'Connor, MD, PhD, Director of Lymphoid Malignancies, Professor of
Medicine and Experimental Therapeutics at Columbia Medical Center, New
York Presbyterian Medical Center, one of the lead investigators in the
BELIEF study. "Relapse is common after initial treatment, and there are
limited options for patients in 2nd line and beyond. Histone
deacetylase inhibitors have emerged as one promising class of drugs for
patients faced with this disease. One interesting observation in the
study was the tolerability of Beleodaq in these heavily treated
patients. Beleodaq was associated with myelosuppression with an overall
rate of anemia of 32%, thrombocytopenia of 16.3% and neutropenia of 9.3%
and Grade 3/4 adverse reactions were reported in 10.9%, 7.0% and 6.2% of
patients, respectively. The associated severity of hematologic
toxicities may prove to be useful in previously treated patients who
have poor bone marrow reserve."
"Interestingly, Beleodaq was shown to have an Overall Response Rate of
25.8% with a high response rate (45.5%) in patients with
Angioimmunoblastic T-cell Lymphoma, one of the common PTCL subtypes. In
addition, 17% of the patients enrolled in this trial had low Baseline
platelet counts ( < 100,000/mm3) and tolerated therapy with
some (15%) attaining partial and complete responses. I believe Beleodaq
will be a valuable new option for physicians who treat patients with
relapsed or refractory PTCL. This safety profile makes it a potential
candidate for the development of new combination treatment paradigms for
patients with PTCL," added Dr. O'Connor.
A review of data from a planned confirmatory Phase III trial of Beleodaq
in combination with CHOP (cyclophosphamide, vincristine, doxorubicin,
prednisone), to characterize the efficacy and safety of the Beleodaq
combination versus CHOP alone, is required by FDA to convert this
Accelerated Approval to a Full Approval.
The BELIEF study was an open-label, single-arm, non-randomized,
international trial conducted at 62 centers that enrolled 129 patients
with relapsed or refractory PTCL; 120 patients had histologically
confirmed PTCL by central review and were evaluable for efficacy.
Patients received treatment with Beleodaq (1,000 mg/m2),
administered over 30 minutes via IV infusion, once daily on Days 1-5 of
a 21-day cycle. Treatment cycles were repeated every three weeks until
disease progression or unacceptable toxicity.
The primary efficacy endpoint of the BELIEF study was Overall Response
Rate (complete and partial responses) as assessed by an Independent
Review Committee (IRC) using the International Workshop Criteria (IWC)
(Cheson, 2007). The key secondary efficacy endpoint was Duration of
Response. In all evaluable patients (N = 120) treated with Beleodaq, the
Overall Response Rate (CR + PR) per central review using IWC was 25.8%
(n = 31; 95% CI, 18.3 - 34.6); with rates of 23.4% for PTCL, NOS and
45.5% for AITL, the two largest subtypes enrolled. The median Duration
of Response based on the first date of response to disease progression
or death was 8.4 months (95% CI: 4.5 - 29.4).
Data from the BELIEF study demonstrated that the most common adverse
events (AEs) reported with Beleodaq ( > 25%) were nausea (42%), fatigue
(37%), pyrexia (35%), anemia (32%), and vomiting (29%). Myelosuppression
was observed with an overall rate of anemia of 32%, thrombocytopenia of
16.3% and neutropenia of 9.3%; Grade 3/4 adverse reactions were reported
in 10.9%, 7.0% and 6.2% of patients, respectively. Sixty-one patients
(47.3%) experienced serious adverse reactions while taking Beleodaq or
within 30 days after their last dose of Beleodaq. The most common
serious adverse reactions ( > 2%) were pneumonia (7%), pyrexia (5%),
infection (3%), anemia (2%), increased creatinine (2%), thrombocytopenia
(2%), and multi-organ failure (2%).
Beleodaq is a histone deacetylase (HDAC) inhibitor. HDACs catalyze the
removal of acetyl groups from the lysine residues of histones and some
non-histone proteins. In vitro, belinostat caused the
accumulation of acetylated histones and other proteins, inducing cell
cycle arrest and/or apoptosis of some transformed cells. Belinostat
shows preferential cytotoxicity towards tumor cells compared to normal
cells. Belinostat inhibited the enzymatic activity of histone
deacetylases at nanomolar concentrations ( < 250 nM).
Important Beleodaq Safety Information
Warnings and Precautions
Beleodaq can cause thrombocytopenia, leukopenia (neutropenia and
lymphopenia), and/or anemia; monitor blood counts weekly during
treatment, and modify dosage as necessary.
Serious and sometimes fatal infections, including pneumonia and
sepsis, have occurred with Beleodaq. Do not administer Beleodaq to
patients with an active infection. Patients with a history of
extensive or intensive chemotherapy may be at higher risk of life
Beleodaq can cause fatal hepatotoxicity and liver function test
abnormalities. Monitor liver function tests before treatment and
before the start of each cycle. Interrupt or adjust dosage until
recovery, or permanently discontinue Beleodaq based on the severity of
the hepatic toxicity.
Tumor lysis syndrome has occurred in Beleodaq-treated patients in the
clinical trial of patients with relapsed or refractory PTCL. Monitor
patients with advanced stage disease and/or high tumor burden and take
Nausea, vomiting and diarrhea occur with Beleodaq and may require the
use of antiemetic and antidiarrheal medications.
Beleodaq can cause fetal harm when administered to a pregnant woman.
Women of childbearing potential should be advised to avoid pregnancy
while receiving Beleodaq. If this drug is used during pregnancy, or if
the patient becomes pregnant while taking this drug, the patient
should be apprised of potential hazard to the fetus.
The most common adverse reactions observed in the trial in patients
with relapsed or refractory PTCL treated with Beleodaq were nausea
(42%), fatigue (37%), pyrexia (35%), anemia (32%), and vomiting (29%).
Beleodaq is primarily metabolized by UGT1A1. Avoid concomitant
administration of Beleodaq with strong inhibitors of UGT1A1.
Use in Specific Populations
It is not known whether Beleodaq is excreted in human milk. Because of
the potential for serious adverse reactions in nursing infants from
Beleodaq, a decision should be made whether to discontinue
nursing or discontinue drug, taking into account the importance of the
drug to the mother.
Please see Beleodaq Full Prescribing Information at www.beleodaq.com.
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.
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.
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.
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.
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. With the launch of BELEODAQ, Spectrum
and its affiliates will be marketing five oncology drugs ─ BELEODAQ™
(belinostat) for Injection in the U.S.; FUSILEV® (levoleucovorin) for
Injection in the U.S.; FOLOTYN® (pralatrexate injection), also marketed
in the U.S.; ZEVALIN® (ibritumomab tiuxetan) Injection for intravenous
use, for which the Company has worldwide marketing rights and MARQIBO®
(vinCRIStine sulfate LIPOSOME injection) for intravenous infusion, 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 sales of Spectrum's
drug products, 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 customer concentration,
the possibility for fluctuations in customer orders, evolving market
dynamics, our dependence on third parties for clinical trials,
manufacturing, distribution, information 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®, ZEVALIN® and
MARQIBO® are registered trademarks of Spectrum Pharmaceuticals, Inc and
its affiliates. BELEODAQ™, REDEFINING CANCER CARE™ and the
Spectrum Pharmaceuticals logos are trademarks owned by Spectrum
Pharmaceuticals, Inc. Any other trademarks are the property of
their respective owners.
© 2014 Spectrum Pharmaceuticals, Inc. All Rights Reserved.
Vice President, Strategic
Planning & Investor Relations
Source: Spectrum Pharmaceuticals
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