THOUSAND OAKS, Calif.,
Dec. 6, 2014 /PRNewswire/
-- Amgen (NASDAQ:AMGN) today announced new data from the Phase
2 BLAST study which evaluated the bispecific T cell engager
(BiTE®) immunotherapy BLINCYTO™ (blinatumomab) in
patients with minimal residual disease (MRD) positive B-cell
precursor acute lymphoblastic leukemia (ALL). In the study, 78
percent of patients who received BLINCYTO experienced a complete
MRD response (95 percent CI: 69-85 percent), a measure of
eradication of residual disease at the molecular level, after one
treatment cycle. Nearly all complete responses (98 percent)
occurred within the first treatment cycle.
The results from the BLAST study (Study '203; abstract #
379) will be featured during the 56th American
Society of Hematology (ASH) Annual Meeting and Exposition press
briefing on Saturday, December 6, at
10 a.m. PT and will be presented in
an oral session at ASH on Monday, December
8, at 10:30 a.m. PT.
"BLINCYTO is the most advanced of Amgen's
BiTE® immunotherapies, a new and innovative
approach that helps the body's own immune system fight cancer,"
said Sean E. Harper, M.D., executive
vice president of Research and Development at Amgen. "Achieving
molecular complete remission is an important goal in the treatment
of ALL, and the data presented at ASH demonstrates that BLINCYTO
can produce deep responses in patients that have trace amounts of
residual disease."
MRD is a state of disease in which the microscopic analysis does
not show malignant cells, but more sensitive techniques still
detect disease at the molecular level.1 Patients who
have persistent or recurrent MRD after their first therapy have a
higher risk of relapse than those with no detectable
MRD.1
In addition to the majority (78 percent) of patients achieving a
compete MRD response within one cycle of treatment, 80 percent
achieved a complete MRD response across all cycles. Responses
occurred in all subgroups including older patients and patients
with high MRD level; no predictive factor for MRD response was
identified.
In the study, adverse events (AEs) of all grades occurring in 20
percent or more patients included pyrexia (90 percent), tremor (29
percent), chills (26 percent), fatigue (24 percent), nausea (22
percent), vomiting (22 percent) and diarrhea (20 percent).
Grade ≥3 AEs occurring in five percent or more patients included
neutropenia (16 percent), pyrexia (7 percent) and tremor (5
percent). Two fatal AEs occurred on treatment: subdural hemorrhage
and pneumonitis in conjunction with influenza (the latter was
deemed treatment-related). Treatment interruptions due to AEs
occurred in 31 percent of patients.
BLAST Phase 2 Trial Design
The BLAST study is the
largest prospective trial in patients with MRD-positive ALL. It is
an open-label, multicenter, confirmatory single-arm, Phase 2 study
evaluating the efficacy, safety and tolerability of BLINCYTO in
adult patients (≥18 years) with MRD positive B-cell precursor ALL
in hematologic complete remission (<5 percent blasts in bone
marrow) after three or more intensive chemotherapy treatments.
Patients received continuous IV infusion of 15 μg/m2/d
for four weeks, followed by two weeks off. Patients received up to
four cycles of treatment, or could undergo a hematopoietic stem
cell transplantation (HSCT) at any time after the first cycle, if
eligible. The primary endpoint is rate of complete MRD
response. Secondary endpoints include incidence and severity of AE,
hematological relapse-free survival rate, overall survival, time to
hematologic relapse, and duration of complete MRD response.
About BLINCYTO™ (blinatumomab)
BLINCYTO is the first
BiTE® antibody construct and the first single-agent
immunotherapy to be approved by the U.S. Food and Drug
Administration (FDA).2 BLINCYTO was granted breakthrough
therapy and priority review designations by the FDA, and is now
approved in the U.S. for the treatment of Philadelphia chromosome-negative (Ph-)
relapsed or refractory B-cell precursor acute lymphoblastic
leukemia (ALL).
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 (25%), febrile neutropenia (25%), nausea (25%), hypokalemia
(23%), rash (21%), tremor (20%) and constipation (20%).
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 the world's largest
independent biotechnology company, 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
This news 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 risks, uncertainties
and assumptions that could cause actual results to differ
materially from those described. All statements, other than
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metrics, expected legal, arbitration, political, regulatory or
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estimates and results. Forward-looking statements involve
significant risks and uncertainties, including 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
Inc.'s most recent Forms 10-K, 10-Q and 8-K for additional
information on the uncertainties and risk factors related to our
business. Unless otherwise noted, Amgen is providing this
information as of Dec. 6, 2014, and
expressly disclaims any duty to update information contained in
this news release.
No forward-looking statement can be guaranteed and actual
results may differ materially from those we project. Discovery or
identification of new product candidates or development of new
indications for existing products cannot be guaranteed and movement
from concept to product is uncertain; consequently, there can be no
guarantee that any particular product candidate or development of a
new indication for an existing product will be successful and
become a commercial product. Further, preclinical results do not
guarantee safe and effective performance of product candidates in
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sometimes, even adequately modeled by computer or cell culture
systems or animal models. The length of time that it takes for us
and our partners to complete clinical trials and obtain regulatory
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In addition, sales of our products (including products of our
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believe that some of our newer products, product candidates or new
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and our partners routinely obtain patents for our
and their products and technology, the protection of our
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We may experience difficulties, delays or unexpected costs and not
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The scientific information discussed in this news release
related to our product candidates is preliminary and investigative.
Such product candidates are not approved by the U.S. Food and Drug
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CONTACT: Amgen
Kristen
Davis, 805-447-3008 (media)
Danielle Bertrand, 650-266-2114
(media)
Arvind Sood, 805-447-1060
(investors)
References:
1 National Comprehensive Cancer Network. "Acute
Lymphoblastic Leukemia." Available at:
http://www.alabmed.com/uploadfile/2014/0214/20140214092732754.pdf.
Accessed on October 27, 2014.
2 NCCN Clinical Practice Guidelines in Oncology (NCCN
Guidelines®): Acute Lymphoblastic Leukemia. Version 1.2014.
Available at:
https://www.nccn.org/store/login/login.aspx?ReturnURL=http://www.nccn.org/professionals/physician_gls/pdf/all.pdf.
Accessed on November 24, 2014.
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