THOUSAND OAKS, Calif.,
Dec. 8, 2014 /PRNewswire/
-- Amgen (NASDAQ: AMGN) today announced that new data
from a pivotal Phase 2 study evaluating BLINCYTO™
(blinatumomab) for the treatment of adult patients with
relapsed/refractory B-cell precursor acute lymphoblastic leukemia
(ALL) was presented at the 56th American Society of
Hematology (ASH) Annual Meeting and Exposition.
In one analysis from the '211 study, 40 percent of patients
treated with BLINCYTO who achieved a complete remission (CR) or
complete remission with partial hematologic recovery (CRh) were
enabled to proceed to allogeneic hematopoietic stem cell transplant
(HSCT). Additionally, a secondary analysis from the study found
that 82 percent of patients who had a CR or CRh also had a minimal
residual disease (MRD) response, a measure used to predict disease
recurrence in patients with ALL.
"The data from the '211 study expand the evidence of Amgen's
BiTE® immunotherapy as an advance in the management of
this difficult-to-treat cancer, and importantly, served as the
basis for the recent U.S. Food and Drug Administration (FDA)
approval of BLINCYTO," said Sean E.
Harper, M.D., executive vice president of Research and
Development at Amgen. "In this study, BLINCYTO helped patients
bridge to a stem cell transplant after achieving a remission, a key
goal in the management of ALL, and achieved MRD response in
patients, an important parameter in predicting relapse."
In the study, the most frequent grade >3 adverse
events (AEs) occurring in >5 percent of patients were
febrile neutropenia (25 percent), neutropenia (16 percent), anemia
(14 percent), pneumonia (9 percent), thrombocytopenia (8 percent),
hyperglycemia (8 percent), leukopenia (8 percent), alanine
aminotransferase increased (7 percent), hypokalemia (7 percent),
pyrexia (7 percent), sepsis (6 percent), hypophosphatemia (5
percent). Grade > 3 neurologic events occurred in 13
percent of patients, and grade > 3 cytokine release syndrome
occurred in 2 percent of patients.
ASH Abstract 965: Allogeneic Hematopoietic Stem Cell
Transplantation Following anti-CD19 BiTE® Blinatumomab
in Adult Patients with Relapsed/Refractory B-precursor Acute
Lymphoblastic Leukemia
In one analysis of the '211 study, 40 percent of patients treated
with BLINCYTO who achieved a CR or CRh were enabled to proceed to
HSCT, including both patients who had received prior HSCT and
patients who had not received prior HSCT. Additionally, the
analysis found that responses to BLINCYTO were similar between
patients who had received prior HSCT and patients who had not
received HSCT (45 percent versus 42 percent, respectively).
ASH Abstract 3704: An Evaluation of Molecular Response in a
Phase 2 Open-Label, Multicenter Confirmatory Study in Patients With
Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia
Receiving Treatment with the BiTE® antibody construct
Blinatumomab
A secondary analysis of the study demonstrated that, among patients
receiving BLINCYTO who had a CR or CRh and had evaluable MRD data
(n=73), 82 percent had an MRD response, with 70 percent of those
patients achieving a complete MRD response. Median overall survival
was longer among patients who had a CR or CRh and an MRD response
compared to patients who didn't have an MRD response (11.5 months
[95 percent CI, 8.5 – not estimable] versus 6.7 months [95 percent
CI, 2.0 – not estimable], respectively).
In the U.S., more than 6,000 cases of ALL will be diagnosed in
2014, and in the European Union, it is estimated that more than
7,000 cases of ALL are diagnosed each year.1,2 In
adult patients with relapsed or refractory ALL, median overall
survival is just three to five months.3
'211 Phase 2 Trial Design
The single arm, open-label, multicenter Phase 2 trial evaluated the
safety and efficacy of BLINCYTO in adult patients with Philadelphia chromosome-negative (Ph-)
B-precursor ALL who had relapsed or were refractory following
treatment with standard front-line chemotherapy or allogeneic stem
cell transplant. Patients received up to five four-week cycles of
intravenous BLINCYTO treatment. The primary endpoint of the study
was the rate of CR/CRh within the first two treatment cycles.
Secondary endpoints include duration of CR and CRh, relapse-free
survival, overall survival, HSCT realization rate, 100-day
mortality rate and adverse events.
About BLINCYTO™ (blinatumomab)
BLINCYTO is the first BiTE® antibody construct and the first
single-agent immunotherapy to be approved by the U.S.
FDA.4 BLINCYTO was granted breakthrough therapy and
priority review designations by the FDA, and is now approved in the
U.S. for the treatment of 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
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this information as of Dec. 8, 2014,
and expressly disclaims any duty to update information contained in
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identification of new product candidates or development of new
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CONTACT: Amgen
Kristen Davis,
805-447-3008 (media)
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(media)
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(investors)
1 American Cancer Society. "Leukemia-Acute
Lymphocytic." Available at:
http://www.cancer.org/cancer/leukemia-acutelymphocyticallinadults/detailedguide/leukemia-acute-lymphocytic-key-statistics.
Accessed October 20, 2014.
2 Gatta G, Maarten van der Zwan J, Casali P, et. al.
Rare cancers are not so rare: The rare cancer burden in
Europe. Eur J Cancer.
2011;47:2493-2511.
3 Advani A.S. New
immune strategies for the treatment of acute lymphoblastic
leukemia: Antibodies and chimeric antigen receptors. Hematology Am
Soc Hematol Educ Program. 2013;2013:131-7. Retrieved from:
http://asheducationbook.hematologylibrary.org/content/2013/1/131.long.
Accessed October 20, 2014.
4 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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