THOUSAND OAKS, Calif.,
Feb. 14, 2018 /PRNewswire/
-- Amgen (NASDAQ:AMGN) today announced that the Oncologic
Drugs Advisory Committee of the U.S. Food and Drug Administration
(FDA) will review data supporting the BLINCYTO®
(blinatumomab) supplemental Biologics License Application (sBLA)
for the treatment of patients with minimal residual disease
(MRD)-positive B-cell precursor acute lymphoblastic leukemia (ALL)
at a meeting on March 7, 2018.
MRD refers to the presence of a small amount of detectible
cancer cells that remain in the patient after treatment.
"After achieving remission, the presence of MRD is the strongest
prognostic factor for relapse in acute lymphoblastic leukemia.
However, today up to half of patients remain MRD-positive after
induction treatments and receive limited clinical benefit from
treatments like chemotherapy or stem cell transplantation as a
result of failure to identify and treat this residual disease,"
said David M. Reese, M.D., senior
vice president of Translational Sciences and Oncology at Amgen.
"Currently there are no approved therapies for patients with
MRD-positive ALL, representing a significant unmet need. This sBLA
for BLINCYTO is the first application to ever be submitted for an
MRD positive indication, and we look forward to discussing the
supporting data with members of the Committee."
The Committee will review results from clinical studies in
support of this potential new indication, including results from
the Phase 2 BLAST study evaluating patients with B-cell precursor
ALL and persistent or recurrent MRD after at least three cycles of
intensive chemotherapy.
BLINCYTO is the first-and-only approved bispecific CD19-directed
CD3 T cell engager (BiTE®) immunotherapy. It is also the
first bispecific antibody construct
from Amgen's BiTE® platform, which helps the
body's immune system target cancer cells and represents an entirely
new area of oncology research.
The sBLA for BLINCYTO was accepted by the FDA for priority
review, and a Prescription Drug User Fee Act (PDUFA) target action
date of March 29, 2018 has been
set.
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 FDA in 2014 for the
treatment of relapsed or refractory B-cell precursor ALL in
adults and children, and is now approved in the U.S. for this
indication.
In November 2015, BLINCYTO was granted conditional
marketing authorization in the European Union for the treatment of
adults with Philadelphia
chromosome-negative (Ph-) relapsed or refractory B-cell precursor
ALL. Additional regulatory applications for BLINCYTO are underway
and have been submitted to health authorities worldwide.
About the BLAST Study
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 with MRD-positive B-cell precursor ALL in complete
hematologic remission after three or more cycles of intensive
chemotherapy treatments and a presence of MRD. 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 was the rate of complete MRD
response within the first treatment cycle. The key secondary
endpoint was relapse-free survival at 18 months. Additional
secondary endpoints include incidence and severity of adverse
events, overall survival (OS), time to hematological remission and
duration of complete MRD response. Results from the BLAST study
were presented at the 57th Annual Meeting and Exposition
of the American Society of Hematology in 2015.
About ALL and MRD
ALL is a rare and rapidly
progressing cancer of the blood and bone marrow that occurs in both
adults and children.1,2 Many adult patients with
ALL relapse, often within one year of their diagnosis, from which
the median survival is only 4 to 8
months.3 Poor outcomes have been observed in
patients who relapse after achieving a complete response but have
persistent MRD, with 5-year OS rates as high as 75 percent for
patients that achieve MRD-negative status, compared with 33 percent
among patients that remain MRD-positive.4 In pediatric
patients, MRD-positive status after treatment is associated with a
15-times higher risk of relapse compared with those with
undetectable residual disease.5
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 bridge T cells to tumor cells,
using the patient's own immune system to eradicate their cancer.
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.
BLINCYTO® U.S. Product Safety
Information
Indication and Important Safety Information, including Boxed
WARNINGS, for BLINCYTO® (blinatumomab) for
injection, for intravenous use
INDICATION
BLINCYTO® is indicated for the treatment of
relapsed or refractory B-cell precursor acute lymphoblastic
leukemia (ALL) in adults and children.
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): CRS, which may be
life-threatening or fatal, 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 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® 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): 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 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 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 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
in Philadelphia chromosome-negative relapsed or
refractory B-cell precursor ALL (TOWER Study) (≥ 20%) in the
BLINCYTO® arm 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
practices, reimbursement activities and outcomes and other such
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 successful, regulatory authorities may question
the sufficiency for approval of the trial endpoints we have
selected. We develop product candidates internally and through
licensing collaborations, partnerships and joint ventures. Product
candidates that are derived from relationships may be subject to
disputes between the parties or may prove to be not as effective or
as safe as we may have believed at the time of entering into such
relationship. Also, we or others could identify safety, side
effects or manufacturing problems with our products, including our
devices, after they are on the market.
Our results may be affected by our ability to successfully
market both new and existing products domestically and
internationally, clinical and regulatory developments involving
current and future products, sales growth of recently launched
products, competition from other products including biosimilars,
difficulties or delays in manufacturing our products and global
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for a portion of our manufacturing activities, and limits on supply
may constrain sales of certain of our current products and product
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with respect to many of our marketed products as well as for the
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problems with a product similar to one of our products that
implicate an entire class of products could have a material adverse
effect on sales of the affected products and on our business and
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repurchase our common stock.
The scientific information discussed in this news release
relating to new indications for our products is preliminary and
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Food and Drug Administration for the products. The products are not
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safety or effectiveness of the products for these uses.
CONTACT: Amgen, Thousand
Oaks
Kristen Davis, 805-447-3008
(Media)
Kristen Neese, 805-313-8267
(Media)
Arvind Sood, 805-447-1060
(Investors)
References:
- Cancer Research UK. About acute lymphoblastic leukaemia (ALL).
http://www.cancerresearchuk.org/about-cancer/acute-lymphoblastic-leukaemia-all/about.
Accessed Dec. 5, 2017.
- Mayo Clinic. Acute lymphocytic leukemia.
http://www.mayoclinic.org/diseases-conditions/acute-lymphocytic-leukemia/basics/definition/con-20042915.
Accessed Dec. 5, 2017.
- Katz A, Chia V, Schoonen M, et al. Acute lymphoblastic
leukemia: an assessment of international incidence, survival, and
disease burden. Cancer Causes Control.
2015;26:1627-1642.
- Bassan R, Spinelli O, Oldani E, et al. Improved risk
classification for risk-specific therapy based on the molecular
study of minimal residual disease (MRD) in adult acute
lymphoblastic leukemia (ALL). Blood. 2009:113:
4153-4162.
- Cavé H, van der Werff ten Bosch J, Suciu S, et al. Clinical
Significance of Minimal Residual Disease in Childhood Acute
Lymphoblastic Leukemia. N Engl J Medicine.1998:339:
591-598.
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