- Early Action before PDUFA date of
August 9, 2014 follows Priority Review
- Beleodaq to be launched through
Spectrum's existing sales force
- Beleodaq is expected to be available
to patients in less than 3 weeks
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 confirmatory trial.
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 growth.”
“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.
BELIEF STUDY
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%).
About BELEODAQ™
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 threatening infections.
- 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 appropriate
precautions.
- 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.
Adverse Reactions
- 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%).
Drug Interactions
- 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.
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.
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 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.
Spectrum PharmaceuticalsShiv KapoorVice President, Strategic
Planning & Investor
Relations702-835-6300InvestorRelations@sppirx.com
Spectrum Pharmaceuticals (NASDAQ:SPPI)
Historical Stock Chart
From Mar 2024 to Apr 2024
Spectrum Pharmaceuticals (NASDAQ:SPPI)
Historical Stock Chart
From Apr 2023 to Apr 2024