Results support the safety and efficacy of high-dose Captisol-enabled
(CE)-Melphalan as a high-dose conditioning treatment prior to
autologous hematopoietic stem cell transplantation (AHCT) in patients
with multiple myeloma (MM).
Overall Response Rate improved from 79% at study entry to 95% after
CE-Melphalan and AHCT; Complete Response Rate increased from 10 to 31%.
Spectrum's CE-Melphalan formulation is free of propylene glycol and
does not use a custom, propylene glycol-containing solvent for its
CE-Melphalan is more stable with a longer use time, simplifying
clinical administration logistics.
CE-Melphalan was shown to be bioequivalent to the currently approved
commercial intravenous formulation of melphalan.
FDA decision is expected in late 2015. If approved, the Company plans
to launch CE-Melphalan with its existing hematology/oncology sales
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 results
of a clinical study of Propylene Glycol (PG)-Free, Captisol-enabled
Melphalan (CE Melphalan) Conditioning for Autologous Hematopoietic Stem
Cell Transplantation (AHCT) in Patients with Multiple Myeloma (MM).
Spectrum filed a New Drug Application (NDA) for approval of CE-Melphalan
in December 2014 and expects a decision from the Food and Drug
Administration (FDA) by late 2015.
"CE-Melphalan is a key late-stage drug for the company, and we are
excited to share these clinical data," said Rajesh C. Shrotriya, MD,
Chairman and Chief Executive Officer of Spectrum Pharmaceuticals.
"CE-Melphalan is a new injectable formulation of melphalan that
incorporates the Captisol brand of β-cyclodextrin improving the
solubility and stability of melphalan. It also facilitates the use of an
aqueous diluent (normal saline) instead of propylene glycol, which is
associated with toxicities including renal dysfunction and arrhythmias.
CE-Melphalan will fit seamlessly into our existing commercial
infrastructure if it is approved by the FDA. Spectrum is committed to
deliver improved treatment options to patients suffering with cancer."
"Intravenous melphalan has become the standard of care conditioning
agent used for high-dose treatment of MM patients undergoing AHCT, and
the substitution of Captisol in CE-Melphalan addresses some of the
limitations of the currently approved formulations," said Dr.
Parameswaran Hari, Armand J. Quick/William F. Stapp Professor of
Hematology at the Medical College of Wisconsin, Director of the Adult
Blood and Marrow Transplant Program at Froedtert Hospital and the
Section Head of Hematologic Malignancies and Transplantation, in the
Division of Hematology and Oncology in the Department of Medicine. "The
improved stability of the CE-Melphalan HCl formulation may potentially
ensure that cancer patients receive the full, intended therapeutic dose
of IV melphalan by increasing the use time and infusion time of IV
Melphalan, and simplifying clinical administration logistics."
Following is the summary of the presentation:
Abstract #155 Results of a Phase II Study of Propylene Glycol
(PG)-Free, Captisol-Enabled Melphalan Conditioning for Autologous
Hematopoietic Stem Cell Transplantation (AHCT) in Patients with Multiple
Sixty-one patients with MM received 200 mg/m2 of CE-Melphalan
(100 mg/m2/day x 2) followed by AHCT. The number of lines of
prior therapy ranged from 1 to 4, and 9 (15%) pts had high risk
cytogenetics. Disease status Pre-treatment included Complete Response
(CR) in 10% of subjects, Very Good Partial Response (VGPR) in 36% and
Partial Response (PR) in 33% subjects. All subjects (100%) achieved
myeloablation followed by successful bone marrow engraftment. Median
time to neutrophil engraftment was 12 days and to platelet engraftment
was 13 days post-AHCT. There were no deaths by Day 100, and the most
common Grade 3 and 4 toxicities were the expected hematologic events
(neutropenia, leukopenia, lymphopenia, thrombocytopenia and anemia). The
most frequent non-hematologic adverse events included diarrhea, nausea,
and fatigue. Importantly, the incidence of severe mucositis was low
(Grade 3/4; 10%). At Day 100 post-AHCT, the ORR increased to 95% with
74% of subjects achieving a > = VGPR response including stringent CR in
16%, CR in 15% and VGPR in 43%.
Conclusions: CE-Melphalan led to successful myeloablation and
subsequent engraftment in MM patients with no mortality or unexpected
transplant-related toxicity; the incidence of Grade 3-4 mucositis was
low. Overall, 95% of subjects (n=61) responded to high dose
CE-Melphalan, and in the subgroup of high risk patients (15%), 67% VGPR
or better responses were achieved.
In December 2014, Spectrum submitted a NDA to the FDA for the approval
of CE-Melphalan (propylene glycol-free) for use as a high-dose
conditioning treatment prior to AHCT in patients with MM. Spectrum is
also seeking approval for the palliative treatment of patients with MM
for whom oral therapy is not appropriate.
Spectrum Pharmaceuticals gained global development and commercialization
rights to CE-Melphalan from Ligand Pharmaceuticals Incorporated (NASDAQ:
LGND) in March 2013. Spectrum assumed the responsibility for the pivotal
clinical trial and was responsible for filing the NDA. Under the license
agreement, Ligand received a license fee and is eligible to receive
milestone payments, as well as royalties following potential
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
five oncology drugs─ 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;
MARQIBO® (vinCRIStine sulfate LIPOSOME injection) for
intravenous infusion, for which the Company has worldwide marketing
rights and BELEODAQ® (belinostat) for Injection in the
U.S. 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.
About Captisol-Enabled Melphalan
Captisol-Enabled, Propylene Glycol -free Melphalan is a novel
intravenous formulation of melphalan being investigated for the multiple
myeloma transplant setting, for which it has been granted an Orphan Drug
Designation by the FDA. This formulation eliminates the need to use
propylene glycol containing custom diluent, which has been reported to
cause renal and cardiac side effects, which in turn limit the ability to
deliver higher doses of therapeutic compounds. The use of the Captisol®
technology to reformulate melphalan also improves its stability and is
anticipated to allow for slower infusion rates and longer administration
durations, potentially enabling clinicians to safely achieve a higher
dose intensity for pre-transplant chemotherapy.
Captisol is a patent-protected, chemically modified cyclodextrin with a
structure designed to optimize the solubility and stability of drugs.
Captisol was invented and initially developed by scientists in the
laboratories of Dr. Valentino Stella at the University of Kansas'
Higuchi Biosciences Center for specific use in drug development and
formulation. This unique technology has enabled six FDA-approved
products, including Onyx Pharmaceuticals' Kyprolis®, Baxter
International's Nexterone® and Merck's NOXAFIL IV. There are
also more than 30 Captisol-enabled products currently in clinical
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®, ZEVALIN®, MARQIBO®,
and BELEODAQ® 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. Any other trademarks are the property of
their respective owners.
© 2015 Spectrum Pharmaceuticals, Inc. All Rights Reserved
Vice President, Strategic
Planning & Investor Relations
Source: Spectrum Pharmaceuticals
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