THOUSAND OAKS, Calif.,
June 19, 2018 /PRNewswire/ -- Amgen
(NASDAQ:AMGN) today announced that the European Commission (EC) has
granted a full marketing authorization for
BLINCYTO® (blinatumomab) based on the overall
survival (OS) data from the Phase 3 TOWER study in adult patients
with Philadelphia
chromosome-negative (Ph-) relapsed or refractory B-cell precursor
acute lymphoblastic leukemia (ALL).
"BLINCYTO is the first single agent immunotherapy to demonstrate
superior overall survival benefit over standard of care," said
David M. Reese, M.D., senior vice
president of Translational Sciences and Oncology at Amgen. "For
decades, overall survival has been the gold standard for assessing
the efficacy of treatments for blood cancers. The near doubling of
median overall survival versus standard of care seen in the TOWER
study is groundbreaking and reinforces BLINCYTO as a highly
effective ALL therapy, providing physicians with a much needed,
efficacious treatment option, potentially offering patients the
chance to live longer."
BLINCYTO is the first-and-only bispecific CD19-directed CD3 T
cell engager (BiTE®) immunotherapy construct approved
globally. It is also the first bispecific immunotherapy from
Amgen's BiTE® platform, an innovative approach that
helps the body's immune system target cancer cells.
In the TOWER study, BLINCYTO demonstrated a superior improvement
in median OS over standard of care (SOC) chemotherapy. Median OS
was 7.7 months (95 percent CI: 5.6, 9.6) for BLINCYTO versus four
months (95 percent CI: 2.9, 5.3) for SOC (HR for death=0.71;
p=0.012). For patients treated in first salvage, the median
OS was 11.1 months for BLINCYTO versus 5.3 months for SOC (HR=0.6,
95 percent CI: 0.39, 0.91). Safety results among subjects who
received BLINCYTO were comparable to those seen in the previous
Phase 2 studies of BLINCYTO in adult patients with Ph- relapsed or
refractory B-cell precursor ALL.
Approval via the centralized procedure allows for obtaining a
marketing authorization from the EC, which is valid in all European
Union (EU) and European Economic Area (EEA)-European Free Trade
Association (EFTA) states (Norway,
Iceland and Liechtenstein).
About TOWER
The TOWER study was a Phase 3, randomized,
active-controlled, open-label study investigating the efficacy of
BLINCYTO versus SOC chemotherapy in 405 adult patients
with Ph- relapsed or refractory B-cell precursor ALL. The
study enrolled a difficult-to-treat patient population which
included patients at several states of relapse. In the BLINCYTO
arm, this included 35 percent of patients that had relapsed
post-allogenic hematopoietic stem cell transplant (alloHSCT), and
excluded those with late first relapse (≥12 months after initial
remission). Patients were randomized in a 2:1 ratio to receive
BLINCYTO (n=271) or treatment with investigator choice of SOC
chemotherapy (n=134). The determination of efficacy was based on
OS. Per the recommendation of an independent data monitoring
committee, Amgen ended the study early for evidence of
superior efficacy in the BLINCYTO arm versus SOC chemotherapy.
These results were published in The New England Journal of
Medicine.
About Adult ALL in Europe
ALL is a rare and rapidly
progressing cancer of the blood and bone
marrow.1,2 The incidence of adult ALL in European
countries is generally between 0.6 to 0.9 per 100,000 persons per
year.3 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.3 Thus, with a population projection of 416
million adults in the EU,4 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.5
About BLINCYTO® (blinatumomab)
BLINCYTO is
a bispecific CD19-directed CD3 T cell engager
(BiTE®) immunotherapy construct that binds
specifically to CD19 expressed on the surface of cells of B-lineage
origin and CD3 expressed on the surface of effector T cells.
BLINCYTO was granted breakthrough therapy and priority review
designations by the FDA in 2014, and carries full approval in
the U.S. for the treatment of relapsed or refractory B-cell
precursor ALL in adults and children. In the U.S., BLINCYTO is also
approved under accelerated approval for the treatment of adults and
children with B-cell precursor ALL in first or second complete
remission with minimal residual disease (MRD) greater than or equal
to 0.1 percent. This indication is approved under accelerated
approval based on MRD response rate and hematological relapse-free
survival (RFS). Continued approval for this indication may be
contingent upon verification and description of clinical benefit in
the confirmatory trials.
In 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 novel
immuno-oncology technology that can theoretically be engineered to
target any surface antigen expressed by any type of cancer. The
modified antibodies are designed to kill malignant cells using the
patient's own immune system, by bridging T cells to tumor cells.
BiTE® antibody constructs connect the T cells to
the targeted cell, with the intent of allowing T cells to inject
toxins which trigger cancer cell death (apoptosis). Amgen is
developing BiTE® antibody constructs to uniquely target
numerous hematologic malignancies and solid tumors.
Important EU BLINCYTO® (blinatumomab)
Safety Information
This product is subject to additional monitoring in the EU.
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 randomized Phase 3 clinical trial (n=267) and in the
single-arm Phase 2 study (n=189) in adults with Ph- relapsed or
refractory B-precursor ALL who received BLINCYTO®. The
most serious adverse reactions that may occur during blinatumomab
treatment include: infections (29.6%), neutropenia/febrile
neutropenia (11.6%), neurologic events (11.6%), cytokine release
syndrome (2.4%), and tumour lysis syndrome (0.9%). The most common
adverse reactions were: infections (63.6%), pyrexia (60.1%),
infusion-related reactions (32.0%), headache (31.1%), febrile
neutropenia (25.7%), anaemia (24.8%), oedema (24.1%), neutropenia
(22.1%), thrombocytopenia (20.4%), increased liver enzymes (16.7%),
cough (16.2%), and rash (16.0%).
Please refer to the Summary of Product Characteristics for
full European prescribing information.
Important Safety Information Regarding BLINCYTO®
(blinatumomab) U.S. 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): CRS, which may be
life-threatening or fatal, occurred in patients receiving
BLINCYTO®. The median time to onset of CRS is 2 days
after the start of infusion. Closely monitor patients for signs and
symptoms of serious adverse events such as fever, headache, nausea,
asthenia, hypotension, increased alanine aminotransferase (ALT),
increased aspartate aminotransferase (AST), increased total
bilirubin (TBILI), and disseminated intravascular coagulation
(DIC). The manifestations of CRS after treatment with BLINCYTO
overlap with those of infusion reactions, capillary leak syndrome
(CLS), and hemophagocytic histiocytosis/macrophage activation
syndrome (MAS). In clinical trials of BLINCYTO, CRS was reported in
15% of patients with relapsed or refractory ALL and in 7% of
patients with MRD-positive ALL. Interrupt or discontinue
BLINCYTO® as outlined in the PI.
- Neurological Toxicities: Approximately 65% of patients
receiving BLINCYTO® in clinical trials experienced
neurological toxicities. The median time to the first event was
within the first 2 weeks of BLINCYTO® treatment and the
majority of events resolved. The most common (≥ 10%) manifestations
of neurological toxicity were headache and tremor. Severe,
life‐threatening, or fatal neurological toxicities occurred in
approximately 13% of patients, including encephalopathy,
convulsions, speech disorders, disturbances in consciousness,
confusion and disorientation, and coordination and balance
disorders. Manifestations of neurological toxicity included cranial
nerve disorders. Monitor patients for signs or symptoms and
interrupt or discontinue BLINCYTO® as outlined in the
PI.
- Infections: Approximately 25% of patients receiving
BLINCYTO® in clinical trials experienced serious
infections such as sepsis, pneumonia, bacteremia, opportunistic
infections, and catheter-site 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), which may be life-threatening or
fatal, 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 (including, but not limited to, white blood cell count
and absolute neutrophil count) 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 with a
median time to onset of 3 days. In patients receiving
BLINCYTO®, although the majority of these events were
observed in the setting of CRS, some cases of elevated liver
enzymes were observed outside the setting of CRS, with a median
time to onset of 19 days. Grade 3 or greater elevations in liver
enzymes occurred in approximately 7% 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.
- Pancreatitis: Fatal pancreatitis has been reported in patients
receiving BLINCYTO® in combination with dexamethasone in
clinical trials and the post-marketing setting. Evaluate patients
who develop signs and symptoms of pancreatitis and interrupt or
discontinue BLINCYTO® and dexamethasone as needed.
- 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 antileukemic 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).
- Immunization: Vaccination with live virus vaccines is not
recommended for at least 2 weeks prior to the start of
BLINCYTO® treatment, during treatment, and until immune
recovery following last cycle of BLINCYTO®.
- Risk of Serious Adverse Reactions in Pediatric Patients due to
Benzyl Alcohol Preservative: Serious and fatal adverse reactions
including "gasping syndrome," which is characterized by central
nervous system depression, metabolic acidosis, and gasping
respirations, can occur in neonates and infants treated with benzyl
alcohol-preserved drugs including BLINCYTO® (with
preservative). When prescribing BLINCYTO® (with
preservative) for pediatric patients, consider the combined daily
metabolic load of benzyl alcohol from all sources including
BLINCYTO® (with preservative) and other drugs containing
benzyl alcohol. The minimum amount of benzyl alcohol at which
serious adverse reactions may occur is not known. Due to the
addition of bacteriostatic saline, 7-day bags of
BLINCYTO® solution for infusion with preservative
contain benzyl alcohol and are not recommended for use in any
patients weighing < 22 kg.
Adverse Reactions
- The most common adverse reactions (≥ 20%) in clinical trial
experience of patients with MRD-positive B-cell precursor ALL
(BLAST Study) treated with BLINCYTO® were pyrexia, infusion related
reactions, headache, infections (pathogen unspecified), tremor, and
chills. Serious adverse reactions were reported in 61% of patients.
The most common serious adverse reactions (≥ 2%) included pyrexia,
tremor, encephalopathy, aphasia, lymphopenia, neutropenia,
overdose, device related infection, seizure, and staphylococcal
infection.
- The most common adverse reactions (≥ 20%) in clinical trial
experience of patients with Philadelphia chromosome-negative relapsed or
refractory B-cell precursor ALL (TOWER Study) treated with
BLINCYTO® were infections (bacterial and pathogen
unspecified), pyrexia, headache, infusion-related reactions,
anemia, febrile neutropenia, thrombocytopenia, and neutropenia.
Serious adverse reactions were reported in 62% of patients. The
most common serious adverse reactions (≥ 2%) included febrile
neutropenia, pyrexia, sepsis, pneumonia, overdose, septic shock,
CRS, bacterial sepsis, device related infection, and
bacteremia.
- Adverse reactions that were observed more frequently (≥ 10%) in
the pediatric population compared to the adult population were
pyrexia (80% vs. 61%), hypertension (26% vs. 8%), anemia (41% vs.
24%), infusion-related reaction (49% vs. 34%), thrombocytopenia
(34% vs. 21%), leukopenia (24% vs. 11%), and weight increased (17%
vs. 6%).
- In pediatric patients less than 2 years old (infants), the
incidence of neurologic toxicities was not significantly different
than for the other age groups, but its manifestations were
different; the only event terms reported were agitation, headache,
insomnia, somnolence, and irritability. Infants also had an
increased incidence of hypokalemia (50%) compared to other
pediatric age cohorts (15-20%) or adults (17%).
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, including Boxed
WARNINGS and Medication Guide, for BLINCYTO®.
About Amgen's Commitment to Oncology
Amgen Oncology is
committed to helping patients take on some of the toughest cancers,
such as those that have been resistant to drugs, those that
progress rapidly through the body and those where limited treatment
options exist. Amgen's supportive care treatments help patients
combat certain side effects of strong chemotherapy, and our
targeted medicines and immunotherapies focus on more than a dozen
different malignancies, ranging from blood cancers to solid tumors.
With decades of experience providing therapies for cancer patients,
Amgen continues to grow its portfolio of innovative and biosimilar
oncology medicines.
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
This news release contains
forward-looking statements that are based on the current
expectations and beliefs of Amgen. All statements, other than
statements of historical fact, are statements that could be deemed
forward-looking statements, including estimates of revenues,
operating margins, capital expenditures, cash, other financial
metrics, expected legal, arbitration, political, regulatory or
clinical results or practices, customer and prescriber patterns 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 reports filed by Amgen, including our most recent annual
report on Form 10-K and any subsequent periodic reports on Form
10-Q and current reports on 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 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
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 obtain regulatory approval for
product marketing has in the past varied and we expect similar
variability in the future. Even when clinical trials are
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product candidates internally and through licensing collaborations,
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we or others could identify safety, side effects or manufacturing
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Our results may be affected by our ability to successfully
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CONTACT:
Amgen, Thousand Oaks
Kristen Davis, 805-447-3008
(Media)
Kristen Neese, 805-313-8267
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Emma Gilbert, +41 413692542
References
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http://www.cancerresearchuk.org/about-cancer/acute-lymphoblastic-leukaemia-all/about.
Accessed November 10,
2017.
- Mayo Clinic. Acute lymphocytic leukemia.
http://www.mayoclinic.org/diseases-conditions/acute-lymphocytic-leukemia/basics/definition/con-20042915.
Accessed November 10, 2017.
- Katz AJ, Chia VM, Schoonen M, et al. Acute lymphoblastic
leukemia: an assessment of international incidence, survival, and
disease burden. Cancer Causes Control.
2015;26(11):1627-42.
- United Nations, Department of Economic and Social Affairs,
Population Division (2013) World Population Prospects: The 2012
Revision.
https://esa.un.org/unpd/wpp/publications/Files/WPP2012_HIGHLIGHTS.pdf.
Accessed November 10, 2017.
- Amgen Data on File.
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