THOUSAND OAKS, Calif.,
July 16, 2015 /PRNewswire/ -- Amgen (NASDAQ:AMGN)
today announced the top-line results of a Phase 2 open-label,
single-arm, multicenter trial to evaluate the efficacy and safety
of BLINCYTO® (blinatumomab) in adults with relapsed or
refractory Philadelphia
chromosome-positive (Ph+) B-cell precursor acute lymphoblastic
leukemia (ALL). The investigational study showed blinatumomab
monotherapy induced a complete remission or complete remission with
partial hematological recovery within two cycles of treatment in a
clinically meaningful number of patients. Overall safety
results from this study were consistent with the known blinatumomab
safety profile.
The data will be submitted to a future medical conference and
for publication.
"These top-line results are encouraging and support blinatumomab
as a potential treatment option for patients with relapsed or
refractory Philadelphia
chromosome-positive B-cell precursor ALL," said Sean E. Harper, M.D., executive vice president
of Research and Development at Amgen. "We are hopeful that our
comprehensive ALL development program for blinatumomab, the first
clinical and regulatory validation of the BiTE®
platform, will continue to demonstrate clinical effectiveness for
patients with this serious disease."
Philadelphia
chromosome-positive B-cell precursor ALL
Approximately
one-fourth of adult ALL expresses the oncogenic
protein BCR-ABL1 that results from the t (9;22)
chromosome translocation known as the Philadelphia chromosome.
Trial Design (NCT02000427)
This study enrolled adult
subjects with relapsed or refractory Ph+ B-cell precursor ALL. This
was an open-label, single-arm, multicenter study consisting of a
screening period, an induction treatment period (two cycles of
blinatumomab), a consolidation treatment period (up to three
additional cycles of blinatumomab for applicable subjects), and a
safety follow-up visit 30 days after treatment. Following the
safety follow-up visit, subjects were followed for response
duration and survival every 3 months for 18 months or death,
whichever occurred first.
About BLINCYTO®
(blinatumomab)
BLINCYTO® (blinatumomab) is
the first bispecific CD19-directed CD3 T cell engager
(BiTE®) antibody construct product, and the first
single-agent immunotherapy to be approved by the U.S. Food and Drug
Administration (FDA) for the treatment of patients with
Philadelphia chromosome-negative
(Ph-) relapsed or refractory B-cell precursor ALL, a rare and
rapidly progressing cancer of the blood and bone
marrow.1,2 Prior to approval, BLINCYTO was granted
breakthrough therapy and priority review designations by the FDA.
BLINCYTO has a BOXED WARNING in its product label regarding
Cytokine Release Syndrome (CRS) and Neurological Toxicities.
(Please see Important Safety Information below).
About BiTE® Technology
Bispecific T
cell engager (BiTE®) antibody constructs are a type of
immunotherapy being investigated for fighting cancer by helping the
body's immune system to detect and target malignant cells. The
modified antibodies are designed to engage two different targets
simultaneously, thereby juxtaposing T cells (a type of white blood
cell capable of killing other cells perceived as threats) to cancer
cells. BiTE® antibody constructs help place the T cells
within reach of the targeted cell, with the intent of allowing T
cells to inject toxins and trigger the cancer cell to die
(apoptosis). BiTE® antibody constructs are currently
being investigated for their potential to treat a wide variety of
cancers. For more information, visit www.biteantibodies.com.
Important U.S. Product
Information
BLINCYTO® is indicated for the
treatment of Philadelphia
chromosome-negative relapsed or refractory B-cell precursor acute
lymphoblastic leukemia (ALL).
This indication is approved under accelerated approval. Continued
approval for this indication may be contingent upon verification of
clinical benefit in subsequent trials.
IMPORTANT SAFETY INFORMATION
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL
TOXICITIES
- Cytokine Release Syndrome (CRS), which may be
life-threatening or fatal, occurred in patients receiving
BLINCYTO®. Interrupt or discontinue
BLINCYTO® as recommended.
- Neurological toxicities, which may be severe,
life-threatening or fatal, occurred in patients receiving
BLINCYTO®. Interrupt or discontinue
BLINCYTO® as recommended.
Contraindications
BLINCYTO® is
contraindicated in patients with a known hypersensitivity to
blinatumomab or to any component of the product formulation.
Warnings and Precautions
- Cytokine Release Syndrome (CRS): Life-threatening or fatal CRS
occurred in patients receiving BLINCYTO®. Infusion
reactions have occurred and may be clinically indistinguishable
from manifestations of CRS. Closely monitor patients for signs and
symptoms of serious events such as pyrexia, headache, nausea,
asthenia, hypotension, increased alanine aminotransferase (ALT),
increased aspartate aminotransferase (AST), increased total
bilirubin (TBILI), disseminated intravascular coagulation (DIC),
capillary leak syndrome (CLS), and hemophagocytic
lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).
Interrupt or discontinue BLINCYTO® as outlined in the Prescribing
Information (PI).
- Neurological Toxicities: Approximately 50% of patients
receiving BLINCYTO® in clinical trials experienced
neurological toxicities. Severe, life-threatening, or fatal
neurological toxicities occurred in approximately 15% of patients,
including encephalopathy, convulsions, speech disorders,
disturbances in consciousness, confusion and disorientation, and
coordination and balance disorders. The median time to onset of any
neurological toxicity was 7 days. Monitor patients for signs or
symptoms and interrupt or discontinue BLINCYTO® as
outlined in the PI.
- Infections: Approximately 25% of patients receiving
BLINCYTO® experienced serious infections, some of which
were life-threatening or fatal. Administer prophylactic antibiotics
and employ surveillance testing as appropriate during treatment.
Monitor patients for signs or symptoms of infection and treat
appropriately, including interruption or discontinuation of
BLINCYTO® as needed.
- Tumor Lysis Syndrome (TLS): Life-threatening or fatal TLS has
been observed. Preventive measures, including pretreatment nontoxic
cytoreduction and on treatment hydration, should be used during
BLINCYTO® treatment. Monitor patients for signs and
symptoms of TLS and interrupt or discontinue BLINCYTO®
as needed to manage these events.
- Neutropenia and Febrile Neutropenia, including life-threatening
cases, have been observed. Monitor appropriate laboratory
parameters during BLINCYTO® infusion and interrupt
BLINCYTO® if prolonged neutropenia occurs.
- Effects on Ability to Drive and Use Machines: Due to the
possibility of neurological events, including seizures, patients
receiving BLINCYTO® are at risk for loss of
consciousness, and should be advised against driving and engaging
in hazardous occupations or activities such as operating heavy or
potentially dangerous machinery while BLINCYTO® is being
administered.
- Elevated Liver Enzymes: Transient elevations in liver enzymes
are associated with BLINCYTO® treatment. The majority of
these events were observed in the setting of CRS. The median time
to onset was 15 days. Grade 3 or greater elevations in liver
enzymes occurred in 6% of patients outside the setting of CRS and
resulted in treatment discontinuation in less than 1% of patients.
Monitor ALT, AST, gamma-glutamyl transferase (GGT), and TBILI prior
to the start of and during BLINCYTO® treatment.
BLINCYTO® treatment should be interrupted if
transaminases rise to > 5 times the upper limit of normal (ULN)
or if TBILI rises to > 3 times ULN.
- Leukoencephalopathy: Although the clinical significance is
unknown, cranial magnetic resonance imaging (MRI) changes showing
leukoencephalopathy have been observed in patients receiving
BLINCYTO®, especially in patients previously treated
with cranial irradiation and anti-leukemic chemotherapy.
- Preparation and administration errors have occurred. Follow
instructions for preparation (including admixing) and
administration in the PI strictly to minimize medication errors
(including underdose and overdose).
Adverse Events
- The most commonly reported adverse reactions (≥ 20%) in
clinical trials were pyrexia (62%), headache (36%), peripheral
edema (26%), febrile neutropenia (26%), nausea (25%), hypokalemia
(23%), rash (21%), tremor (20%) and constipation (20%).
- Serious adverse reactions were reported in 65% of patients. The
most common serious adverse reactions (≥ 2%) included febrile
neutropenia, pyrexia, pneumonia, sepsis, neutropenia,
device-related infection, tremor, encephalopathy, infection,
overdose, confusion, Staphylococcal bacteremia, and
headache.
Dosage and Administration Guidelines
- BLINCYTO® is administered as a continuous
intravenous infusion at a constant flow rate using an infusion pump
which should be programmable, lockable, non-elastomeric, and have
an alarm.
- It is very important that the instructions for preparation
(including admixing) and administration provided in the full
Prescribing Information are strictly followed to minimize
medication errors (including underdose and overdose).
Please see full Prescribing Information and medication guide for
BLINCYTO® at www.BLINCYTO.com
About Amgen
Amgen is committed to unlocking
the potential of biology for patients suffering from serious
illnesses by discovering, developing, manufacturing and delivering
innovative human therapeutics. This approach begins by using tools
like advanced human genetics to unravel the complexities of disease
and understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and
leverages its biologics manufacturing expertise to strive for
solutions that improve health outcomes and dramatically improve
people's lives. A biotechnology pioneer since
1980, Amgen has grown to be one of the world's leading
independent biotechnology companies, has reached millions of
patients around the world and is developing a pipeline of medicines
with breakaway potential.
For more information, visit www.amgen.com and follow
us on www.twitter.com/amgen.
Forward-Looking Statements
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release contains forward-looking statements that are based on the
current expectations and beliefs of Amgen Inc. and its
subsidiaries (Amgen, we or us) and are subject to a number of
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those discussed below and more fully described in
the Securities and Exchange Commission (SEC) reports
filed by Amgen Inc., including Amgen Inc.'s most
recent annual report on Form 10-K and any subsequent periodic
reports on Form 10-Q and Form 8-K. Please refer to Amgen
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No forward-looking statement can be guaranteed and actual
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identification of new product candidates or development of new
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CONTACT: Amgen, Thousand Oaks
Kristen Davis, 805-447-3008
(media)
Arvind Sood, 805-447-1060
(investors)
References
1 Mayo Clinic. "Acute lymphocytic leukemia."
Available at:
http://www.mayoclinic.org/diseases-conditions/acute-lymphocytic-leukemia/basics/definition/con-20042915
Accessed on July 15, 2015.
2 BLINCYTO® US Prescribing
Information.
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