THOUSAND OAKS, Calif.,
Sept. 1, 2016 /PRNewswire/ -- Amgen
(NASDAQ:AMGN) today announced that the U.S. Food and Drug
Administration (FDA) has approved the supplemental Biologics
License Application (sBLA) for BLINCYTO® (blinatumomab)
to include new data supporting the treatment of pediatric patients
with Philadelphia
chromosome-negative (Ph-) relapsed or refractory B-cell precursor
acute lymphoblastic leukemia (ALL). This indication is approved
under accelerated approval, and continued approval may be
contingent upon verification of clinical benefit in subsequent
trials.
The approval is based on results from the Phase 1/2 '205, an
open-label, multicenter, single-arm trial, which evaluated the
efficacy and safety of BLINCYTO in pediatric patients with relapsed
or refractory B-cell precursor ALL.
About Study '205
Study '205 evaluated the safety and
efficacy of BLINCYTO in a Phase 1/2 open-label, multicenter,
single-arm study in 93 pediatric patients with relapsed or
refractory B-cell precursor ALL (second or later bone marrow
relapse, any marrow relapse after allogeneic hematopoietic stem
cell transplantation [alloHSCT], or refractory to other treatments
and had >25 percent blasts in bone marrow). Treatment in this
study has been completed and subjects are being monitored for
long-term efficacy.
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, priority review and
orphan drug designations by FDA, and is now approved in the U.S.
for the treatment of Ph- relapsed or refractory B-cell
precursor ALL.
In November 2015, BLINCYTO was
granted conditional marketing authorization in the European Union
for the treatment of adults with Ph- relapsed or refractory B-cell
precursor ALL.
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): 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 64% of patients
receiving BLINCYTO® in clinical trials experienced
neurological toxicities. The median time to onset of any
neurological toxicity was 4 days. The most common (≥10%)
manifestations of neurological toxicity were headache, tremor,
dizziness, and altered state of consciousness. Severe,
life-threatening, or fatal neurological toxicities occurred in
approximately 17% of patients, including encephalopathy,
convulsions, speech disorders, disturbances in consciousness,
confusion and disorientation, and coordination and balance
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. The
median time to onset of elevated liver enzymes was 3 days. In
patients receiving BLINCYTO®, the majority of these
events were observed in the setting of CRS. The median time to
onset for these events 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.
- 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 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).
- 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®.
Adverse Reactions
- The most common adverse reactions (≥ 20%) in the safety
population studied in clinical trials were pyrexia, headache,
nausea, edema, hypokalemia, anemia, febrile neutropenia,
neutropenia, thrombocytopenia, and abdominal pain. The safety
population included 225 patients weighing 45kg or more and 57
patients weighing less than 45kg.
- In patients weighing greater than or equal to 45kg, serious
adverse reactions were reported in 61% of patients. The most common
serious adverse reactions (≥ 2%) included febrile neutropenia,
pyrexia, sepsis, pneumonia, device-related infection, neutropenia,
tremor, overdose, encephalopathy, infection, confusion and
headache.
- In patients weighing less than 45kg, serious adverse reactions
were reported in 51% of patients. The most common serious adverse
reactions (≥ 2%) included pyrexia, febrile neutropenia, cytokine
release syndrome, convulsion, device-related infection, hypoxia,
sepsis, and overdose
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 pi.amgen.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
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 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 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
economic conditions. In addition, sales of our products are
affected by pricing pressure, political and public scrutiny and
reimbursement policies imposed by third-party payers, including
governments, private insurance plans and managed care providers and
may be affected by regulatory, clinical and guideline developments
and domestic and international trends toward managed care and
healthcare cost containment. Furthermore, our research, testing,
pricing, marketing and other operations are subject to extensive
regulation by domestic and foreign government regulatory
authorities. We or others could identify safety, side effects or
manufacturing problems with our products after they are on the
market. Our business may be impacted by government investigations,
litigation and product liability claims. In addition, our business
may be impacted by the adoption of new tax legislation or exposure
to additional tax liabilities. If we fail to meet the compliance
obligations in the corporate integrity agreement between us and the
U.S. government, we could become subject to significant sanctions.
Further, while we routinely obtain patents for our products and
technology, the protection offered by our patents and patent
applications may be challenged, invalidated or circumvented by our
competitors, or we may fail to prevail in present and future
intellectual property litigation. We perform a substantial amount
of our commercial manufacturing activities at a few key facilities
and also depend on third parties for a portion of our manufacturing
activities, and limits on supply may constrain sales of certain of
our current products and product candidate development. In
addition, we compete with other companies with respect to many of
our marketed products as well as for the discovery and development
of new products. Further, some raw materials, medical devices and
component parts for our products are supplied by sole third-party
suppliers. The discovery of significant 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 results of operations.
Our efforts to acquire other companies or products and to integrate
the operations of companies we have acquired may not be successful.
We may not be able to access the capital and credit markets on
terms that are favorable to us, or at all. We are increasingly
dependent on information technology systems, infrastructure and
data security. Our stock price is volatile and may be affected by a
number of events. Our business performance could affect or limit
the ability of our Board of Directors to declare a dividend or our
ability to pay a dividend or repurchase our common stock.
CONTACT:
Amgen, Thousand Oaks
Kristen Davis, 805-447-3008
(media)
Kristen Neese, 805-313-8267
(media)
Arvind Sood, 805-447-1060
(investors)
Logo - http://photos.prnewswire.com/prnh/20081015/AMGENLOGO
To view the original version on PR Newswire,
visit:http://www.prnewswire.com/news-releases/fda-approves-blincyto-blinatumomab-for-use-in-pediatric-patients-with-philadelphia-chromosome-negative-relapsed-or-refractory-b-cell-precursor-acute-lymphoblastic-leukemia-300321756.html
SOURCE Amgen