THOUSAND OAKS, Calif.,
June 10, 2016 /PRNewswire/ -- Amgen
(NASDAQ:AMGN) today announced new data from a prespecified interim
analysis of the Phase 3 TOWER study, in which BLINCYTO®
(blinatumomab) demonstrated an almost two-fold increase in median
overall survival (OS) compared to standard of care (SOC). The
randomized, open-label TOWER study evaluated the efficacy of
BLINCYTO versus SOC chemotherapy in adult patients with
Philadelphia chromosome-negative
(Ph-) relapsed or refractory B-cell precursor acute lymphoblastic
leukemia (ALL). Results from the analysis showed that median OS was
7.7 months (95 percent CI: 5.6, 9.6) for BLINCYTO versus 4 months
(95 percent CI: 2.9, 5.3) for SOC (stratified log-rank test
p=.012; hazard ratio=0.71). As per the recommendation of an
independent data monitoring committee, Amgen ended the study early
for efficacy based on these results. The data will be presented
during The Presidential Symposium at the 21st Congress
of the European Hematology Association (EHA) in Copenhagen.
"Acute lymphoblastic leukaemia is the most aggressive type of
B-cell malignancy," said Max S.
Topp, M.D., professor and head of haematology, University
Hospital of Wuerzburg, Germany.
"The data presented today not only reinforce the potential of
immunotherapy delivered by T cell engaging bispecific antibody
constructs but also validate the efficacy of BLINCYTO in these
heavily pretreated patients."
Improvement in OS was consistent across subgroups regardless of
age, prior salvage therapy or prior allogeneic stem cell transplant
(alloSCT). Serious adverse events included infection, blood and
lymphatic system disorders, nervous system disorders and cytokine
release syndrome. The BLINCYTO adverse events observed in the TOWER
study were consistent with the known safety profile of
BLINCYTO.
"This is the first study of an immunotherapy to demonstrate
overall survival benefit in adult patients with Ph-negative B-cell
precursor relapsed or refractory ALL, a very complex-to-treat
disease with limited treatment options," said Sean E. Harper, M.D., executive vice president
of Research and Development at Amgen. "BLINCYTO is currently
approved for the treatment of Ph-negative B-cell precursor relapsed
or refractory ALL under accelerated approval, and we look forward
to working with regulatory authorities for a full approval for
BLINCYTO in this patient population."
ALL is a rare and rapidly progressing cancer of the blood and
bone marrow.1,2 Adult patients diagnosed with Ph-
B-cell precursor ALL are often young, with a median age at
diagnosis of 34-39.3,4 Currently, there is no broadly
accepted standard treatment regimen for adult patients with
relapsed or refractory ALL beyond chemotherapy.5 Adults
with relapsed or refractory ALL typically have a very poor
prognosis, with a median OS of three to five
months.6
About the TOWER Study
The TOWER study was a Phase 3,
randomized, open-label study investigating the efficacy of BLINCYTO
versus SOC chemotherapy in adult patients with Ph-relapsed or
refractory B-cell precursor ALL. Patients were randomized in a 2:1
ratio to receive BLINCYTO or treatment with investigator choice of
one of four protocol defined SOC chemotherapy regimens. The primary
endpoint was OS. Secondary endpoints included complete remission
and the combined endpoint of complete remission plus complete
remission with partial or incomplete hematologic recovery.
The TOWER study is the confirmatory trial for BLINCYTO, and
Amgen plans to file for full approval of BLINCYTO based on results
from the study. Click here to read about the trial on
ClinicalTrials.gov.
About Adult ALL
The incidence of adult ALL in
European countries is generally between 0.6 to 0.9 per 100,000
persons per year.7 In the United States (U.S.), the
incidence of adult ALL is approximately 0.9 per 100,000 persons per
year.7 In adult ALL, approximately 75 percent is B-cell
precursor ALL, of which 75-80 percent is Ph- and roughly half will
be refractory to treatment or experience
relapse.7 Thus, with a population projection of 416
million adults in the European Union (EU),8 it is
estimated that the incidence of adult Ph-relapsed or refractory
B-cell precursor ALL in the EU is approximately 900 patients per
year.9 In the U.S., the incidence was approximately 650
patients in 2015.7
About
BLINCYTO® (blinatumomab)
BLINCYTO is a
bispecific CD19-directed CD3 T cell engager (BiTE®)
antibody construct that binds specifically to CD19 expressed on the
surface of cells of B-lineage origin and CD3 expressed on the
surface of T cells.
BLINCYTO was granted breakthrough therapy and priority review
designations by the U.S. Food and Drug Administration (FDA),
and is now approved in the U.S. for the treatment of Ph-
relapsed or refractory B-cell precursor ALL. This indication is
approved under accelerated approval. Continued approval for this
indication may be contingent upon verification of clinical benefit
in subsequent trials.
In November 2015 BLINCYTO was
granted conditional marketing authorization in the EU for the
treatment of adults with Ph- relapsed or refractory B-cell
precursor 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 EU Product Safety Information
This product is subject to additional monitoring in the EU
and EEA. All suspected adverse reactions should be reported in
accordance with the national reporting system.
The adverse reactions described in this section were identified
in the pivotal clinical study (N=189).The most serious adverse
reactions that may occur during blinatumomab treatment include:
infections (31.7%), neurologic events (16.4%), neutropenia/febrile
neutropenia (15.3%) cytokine release syndrome (0.5%), and tumor
lysis syndrome (0.5%). The most common adverse reactions were:
infusion-related reactions (67.2%), infections (63.0%), pyrexia
(59.8%), headache (34.4%), febrile neutropenia (28%), peripheral
edema (25.9%), nausea (24.3%), hypokalaemia (23.8%), constipation
(20.6%), anaemia (20.1%), cough (18.5%), diarrhea (18.0%), tremor
(17.5%), neutropenia (17.5%), abdominal pain (16.9%), insomnia
(15.3%), fatigue (15.3%), and chills (15.3%).
Please refer to the Summary of Product Characteristics for
full European prescribing information.
BLINCYTO® U.S. Product Safety
Information
Important Safety Information Regarding
BLINCYTO® (blinatumomab) U.S. Indication
This safety information is specific to the current U.S. approved
indication.
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 have been 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 with
BLINCYTO® treatment. Follow instructions for preparation
(including admixing) and administration in the PI strictly to
minimize medication errors (including underdose and overdose).
Adverse Reactions
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%), diarrhea (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.
U.S. 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 U.S. 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 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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forward-looking statements that are based on the current
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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 reports filed by Amgen, including our most recent annual
report on Form 10-K and any subsequent periodic reports on Form
10-Q and Form 8-K. Unless otherwise noted, Amgen is providing this
information as of the date of this news release and does not
undertake any obligation to update any forward-looking statements
contained in this document as a result of new information, future
events or otherwise.
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
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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 humans. The complexity of the
human body cannot be perfectly, or sometimes, even adequately
modeled by computer or cell culture systems or animal models. The
length of time that it takes for us to complete clinical trials and
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CONTACT:
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(media)
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Hematology Am Soc Hematol Educ Program. 2013;131-7.
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- United Nations, Department of Economic and Social Affairs,
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- Amgen Data on File.
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