THOUSAND OAKS, Calif.,
May 3, 2016 /PRNewswire/ -- Amgen
(NASDAQ:AMGN) today announced that the U.S. Food and Drug
Administration (FDA) has accepted for priority review the
supplemental Biologics License Application (sBLA) for
BLINCYTO® (blinatumomab) to include new data
supporting the treatment of pediatric and adolescent patients with
Philadelphia chromosome‑negative
(Ph-) relapsed or refractory B-cell precursor acute lymphoblastic
leukemia (ALL).
"Children and adolescents with ALL who experience a second or
greater relapse or are refractory often have a dismal prognosis
with survival rates below 10 percent," said Sean E. Harper, M.D., executive vice president
of Research and Development at Amgen. "The FDA's acceptance of the
sBLA submission for BLINCYTO reinforces immunotherapy as a
potential option for children in need of new treatments to fight
this complex disease and help prevent further relapse."
Priority review is assigned to applications for drugs that treat
serious conditions and would, if approved, provide significant
improvements in the safety or effectiveness of the treatment,
diagnosis or prevention of serious conditions. The Prescription
Drug User Fee Act (PDUFA) target action date is Sept. 1, 2016.
ALL is a rare and rapidly progressing cancer of the blood and
bone marrow impacting both adults and children and is the most
common type of cancer in children.1-3 Of the
approximately 2,500 U.S. children and adolescents diagnosed with
B-cell precursor ALL each year, approximately 15-20 percent
(375-500) will experience relapse or fail to achieve
remission.4-7
The sBLA is based on data from the Phase 1/2 '205 single-arm
trial, which evaluated BLINCYTO in pediatric patients with relapsed
or refractory B-cell precursor ALL. The study met its Phase 2
primary endpoint of complete remission within the first two cycles
of BLINCYTO treatment. Overall, the types of serious adverse
events (AEs) reported in the pediatric population are
consistent with the known BLINCYTO safety profile. The FDA-approved
prescribing information for BLINCYTO includes a boxed warning for
cytokine release syndrome and neurologic toxicities.
About Study '205
Study '205 evaluated BLINCYTO in a
Phase 1/2 single-arm, multicenter, dose-finding, efficacy trial in
patients less than 18 years of age with B-cell precursor ALL that
was refractory, had relapsed at least twice or relapsed after an
allogeneic hematopoietic stem cell transplant (alloHSCT). Treatment
in this study has been completed and subjects are being monitored
for long-term efficacy. The data is being submitted for
publication.
This study included a Phase 1 dose-finding portion and a
Phase 2 portion evaluating safety and efficacy at the
recommended dose (stepwise 5/15-μg/m²/day), which was proposed by
an independent Data Safety Monitoring Board based on data from the
dose-finding portion. The primary Phase 1 endpoint was the
maximum-tolerated dose, defined as the maximum dose at which ≤1 of
six patients experienced a dose-limiting toxicity. Secondary
endpoints included pharmacokinetics and incidence of AEs. The
primary Phase 2 endpoint was complete remission within the first
two cycles of BLINCYTO treatment. Secondary endpoints included
incidence of AEs, proportion undergoing alloHSCT after BLINCYTO
treatment, relapse-free survival and overall survival. Minimal
residual disease (MRD) response and complete MRD response were
exploratory endpoints in both phases.
The most frequent grade ≥3 AEs among the 70 patients who
received the recommended dose were anemia, thrombocytopenia,
febrile neutropenia, hypokalemia and neutropenia.
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, and is
now approved in the U.S. for the treatment of 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 European Union
for the treatment of adults with Ph- relapsed or refractory
B-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
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): 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 have been 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 with
BLINCYTO® treatment. Follow instructions for preparation
(including admixing) and administration in the PI strictly to
minimize medication errors (including underdose and overdose).
Adverse Reactions
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%), diarrhea (20%)
and constipation (20%).
Serious adverse reactions were reported in 65% of patients. The
most common serious adverse reactions (≥ 2%) included febrile
neutropenia, pyrexia, pneumonia, sepsis, neutropenia,
device-related infection, tremor, encephalopathy, infection,
overdose, confusion, Staphylococcal bacteremia, and headache.
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 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 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.
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candidate or development of a new indication for an existing
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human body cannot be perfectly, or sometimes, even adequately
modeled by computer or cell culture systems or animal models. The
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CONTACT:
Amgen, Thousand Oaks
Kristen Davis, 805-447-3008
(media)
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References:
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causes.
http://www.cancerresearchuk.org/about-cancer/type/all/about/acute-lymphoblastic-leukaemia-risks-and-causes.
Accessed March 2, 2016.
- Mayo Clinic. Acute lymphocytic leukemia.
http://www.mayoclinic.org/diseases-conditions/acute-lymphocytic-leukemia/basics/definition/con-20042915.
Accessed March 2, 2016.
- National Cancer Institute. Childhood Acute Lymphoblastic
Leukemia Treatment (PDQ®).
http://www.cancer.gov/types/leukemia/patient/child-all-treatment-pdq.
Accessed March 2, 2016.
- American Cancer Society. Cancer Facts and Figures 2014 Special
Section: Cancer in Children & Adolescents.
http://www.cancer.org/acs/groups/content/@research/documents/webcontent/acspc-041787.pdf.
Accessed March 2, 2016.
- American Cancer Society. How is childhood leukemia classified?
http://www.cancer.org/cancer/leukemiainchildren/detailedguide/childhood-leukemia-how-classified.
Accessed March 2, 2016.
- Pui CH, Behm FG, Crist WM. Clinical and biologic relevance of
immunologic marker studies in childhood acute lymphoblastic
leukemia. Blood;82(2):343-62.
- Hunger SP, Mullighan CG. Acute Lymphoblastic Leukemia in
Children. N Engl J Med. 2015;373(16):1541-52.
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