THOUSAND OAKS, Calif.,
March 29, 2017 /PRNewswire/ -- Amgen
(NASDAQ:AMGN) today announced that the Journal of Clinical
Oncology published results from the Phase 2, open-label
ALCANTARA study evaluating the efficacy and safety of
BLINCYTO® (blinatumomab) in patients with
Philadelphia chromosome-positive
(Ph+) relapsed or refractory B-cell precursor acute lymphoblastic
leukemia (ALL) who had failed at least one second-generation or
later tyrosine kinase inhibitor (TKI). The study, one of the
largest conducted in this patient population (n=45), found that 16
patients (36 percent, 95 percent CI, 22−51 percent) achieved
complete remission or complete remission with partial hematologic
recovery within the first two cycles of treatment, with 14 of the
16 (31 percent, 96 percent CI, 18–47 percent) patients achieving
complete remission with full hematologic recovery.
BLINCYTO is a bispecific CD19-directed CD3 T cell engager
(BiTE®) antibody construct. It is the first bispecific
immunotherapy from Amgen's BiTE® platform, which helps
the body's immune system target cancer cells and represents an
entirely new area of oncology research. BiTE®
immunotherapy is currently being investigated for its potential to
treat a wide variety of cancers.
"Patients with Ph+ relapsed or refractory B-cell precursor ALL
typically have lower remission rates, poor long-term prognosis and
shorter duration of remission than patients with Philadelphia chromosome-negative disease, and
are especially in need of new treatment options beyond TKIs," said
Anthony Stein, M.D., study
investigator and co-director of the Gehr Family Center for Leukemia
Research, City of Hope, Duarte,
Calif. "Results from this Phase 2 study showed blinatumomab
induced complete remission in these high-risk patients regardless
of prior TKI therapy or mutational status, reinforcing the
potential of BiTE® immunotherapy as a targeted therapy
option for this difficult-to-treat patient population."
Among patients who achieved complete remission or complete
remission with partial hematologic recovery within the first two
cycles of treatment, 88 percent had a complete minimal residual
disease (MRD) response, a measure of eradication of residual
disease at the molecular level. Response was consistent regardless
of ABL1 kinase domain mutational status with 40 percent of patients
with a T315I mutation, including those who had received prior
ponatinib, demonstrating a complete remission or complete remission
with partial hematologic recovery. All of these responders also
achieved a complete MRD response.
Additionally, results showed that median relapse-free survival
(RFS) was 6.7 months (95 percent CI, 4.4 to not estimable [NE]
months), with a median follow up of 9.0 months. Median overall
survival (OS) was 7.1 months (95 percent CI, 5.6 to NE months) with
or without censoring for allogeneic hematopoietic stem cell
transplantation (alloHSCT), with a median follow up of 8.8
months.
"The presence of mutations in patients with Ph+ ALL often leads
to relapse and is frequently associated with drug resistance,
underscoring the need for new, more effective treatment options,"
said Sean E. Harper, M.D., executive
vice president of Research and Development at Amgen. "The data
published today in the Journal of Clinical Oncology
found that BLINCYTO demonstrated antileukemic activity in this
heavily pretreated patient population, and we look forward to
working with regulatory authorities to make BLINCYTO available to
patients with this rare and difficult-to-treat type of ALL."
The most frequent adverse events were pyrexia (58 percent),
febrile neutropenia (40 percent) and headache (31 percent). No
incidences of grade 3 or higher cytokine release syndrome were
reported. Three patients had grade 3 neurologic events. There were
no grade 4 or 5 neurologic events.
About the ALCANTARA Study
The ALCANTARA study was a
Phase 2, single-arm, multicenter, open-label study investigating
the efficacy and tolerability of BLINCYTO in 45 adult patients with
Ph+ B-cell precursor ALL, who had relapsed after or were refractory
to at least one second-generation or later TKI, or were intolerant
to second-generation or later TKIs and intolerant or refractory to
imatinib. BLINCYTO was administered in 28-day cycles by continuous
intravenous infusion. The primary endpoint was complete remission
or complete remission with partial hematologic recovery during the
first two cycles. Key secondary endpoints included MRD response,
rate of alloHSCT, RFS, OS and adverse events.
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 Philadelphia chromosome-negative (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.
BLINCYTO® U.S. Product Safety
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®. 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. The neurological toxicity profile varied by age group.
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 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 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®.
Adverse Reactions
- The most common adverse reactions (≥ 20%) in the safety
population studied in clinical trials were pyrexia (66%), headache
(34%), nausea (27%), edema (26%), hypokalemia (26%), anemia (25%),
febrile neutropenia (24%), neutropenia (22%), thrombocytopenia
(20%), and abdominal pain (20%). The safety population included 225
patients weighing 45 kg or more and 57 patients weighing less than
45 kg. For some adverse reactions, there were differences in the
incidence rates by age subgroup.
- In patients weighing greater than or equal to 45 kg, serious
adverse reactions were reported in 61% of patients. The most common
serious adverse reactions (≥ 2%) included febrile neutropenia (9%),
pyrexia (6%), sepsis (5%), pneumonia (5%), device-related infection
(4%), neutropenia (3%), tremor (3%), overdose (3%), encephalopathy
(3%), infection (2%), confusion (3%) and headache (2%).
- In patients weighing less than 45 kg, serious adverse reactions
were reported in 51% of patients. The most common serious adverse
reactions (≥ 2%) included pyrexia (12%), febrile neutropenia (9%),
cytokine release syndrome (4%), convulsion (4%), device-related
infection (4%), hypoxia (4%), sepsis (4%), and overdose (4%).
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 Prescribing Information, including Boxed
WARNINGS and Medication Guide, for
BLINCYTO® at www.BLINCYTO.com.
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
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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. 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,
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CONTACT:
Amgen, Thousand Oaks
Kristen Davis, 805-447-3008
(media)
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(media)
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(investors)
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