THOUSAND OAKS, Calif.,
March 29, 2017 /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 overall
survival (OS) data from the Phase 3 TOWER study. The application
also includes new data supporting the treatment of patients with
Philadelphia chromosome-positive
(Ph+) relapsed or refractory B-cell precursor acute lymphoblastic
leukemia (ALL). The application aims to expand BLINCYTO's
indication for the treatment of all patients with relapsed or
refractory B-cell precursor ALL and supports the conversion of
BLINCYTO's accelerated approval to full approval.
"Patients with relapsed or refractory ALL generally have a very
poor prognosis. The median overall survival – or OS – on standard
of care chemotherapy is just four months," said Sean E. Harper, M.D., executive vice president
of Research and Development at Amgen. "BLINCYTO is the
first-and-only approved bispecific immunotherapy with superior OS
results versus standard of care chemotherapy, nearly doubling the
median OS for patients with this form of ALL. We look forward to
making this important potential new option available to patients
with all forms of relapsed or refractory B-cell ALL."
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 Aug. 14, 2017.
BLINCYTO, the first-and-only FDA-approved CD19-directed CD3
bispecific T cell engager (BiTE®) antibody, was
previously granted breakthrough therapy designation and accelerated
approval. It is also the first single-agent immunotherapy approved
to treat patients with Philadelphia chromosome-negative (Ph-)
relapsed or refractory B-cell precursor ALL.
The application is based on results from the TOWER study,
investigating the efficacy of BLINCYTO versus standard of care
(SOC) chemotherapy in adult patients with Ph- relapsed or
refractory B-cell precursor ALL, which found that BLINCYTO
demonstrated a statistically significant improvement in OS over SOC
chemotherapy, almost doubling median OS. The study showed that
median OS was 7.7 months (95 percent CI: 5.6, 9.6) for BLINCYTO
versus four months (95 percent CI: 2.9, 5.3) for SOC (hazard ratio
for death=0.71; p=0.012). BLINCYTO more than doubled median
OS versus chemotherapy when used early (in first salvage; 11.1
months versus 5.3 months). Per the recommendation of an independent
data monitoring committee, Amgen ended the study early for
efficacy. These results were presented during the Presidential
Symposium at the 21st Congress of
the European Hematology Association and published in the
New England Journal of Medicine.
Safety results among patients who received BLINCYTO were
comparable to those seen in the Phase 2 studies in adult patients
with Ph- relapsed or refractory B-cell precursor ALL. For the most
common adverse events (greater than or equal to 10 percent
incidence rate) in the BLINCYTO arm, only three events (cough,
pyrexia, cytokine release syndrome) occurred at an incidence rate
that was at least five percent higher for BLINCYTO compared to SOC
chemotherapy.
The application also includes data from the ALCANTARA study,
evaluating the efficacy and tolerability of BLINCYTO in adult
patients with Ph+ relapsed or refractory B-cell precursor ALL,
which were published today in the Journal of Clinical
Oncology.
The FDA-approved prescribing information for BLINCYTO includes a
boxed warning for cytokine release syndrome and neurologic
toxicities. BLINCYTO is also under a REMS program in the US.
ALL is a rare and rapidly progressing cancer of the blood and
bone marrow.1,2 Currently, there is no broadly
accepted standard treatment regimen for adult patients with
relapsed or refractory ALL beyond chemotherapy.3 In
adult ALL, approximately 75 percent is B-cell precursor ALL, of
which 75-80 percent is Ph-, and roughly half will be refractory to
treatment or experience relapse.4
About the TOWER Study
The TOWER study was a Phase 3,
randomized, active-controlled, open-label study investigating the
efficacy of BLINCYTO versus SOC chemotherapy in 405 adult patients
with Ph- relapsed or refractory B-cell precursor ALL. The
study enrolled a difficult-to-treat patient population which
included patients from several stages of relapse, 17 percent of
whom had relapsed post-allogenic stem cell transplant (alloSCT),
and excluded those with late first relapse (≥ 12 months after
initial remission). Patients were randomized in a 2:1 ratio to
receive BLINCYTO (n=271) or treatment with investigator choice of
one of four protocol-defined SOC chemotherapy regimens (n=134). The
primary endpoint was OS. Key secondary endpoints included complete
remission within 12 weeks, the combined endpoint of complete
remission plus complete remission with partial or incomplete
hematologic recovery and event-free survival. Other secondary
endpoints included remission duration, minimal residual disease
(MRD) remission (<10–4), alloSCT rate and adverse
event rates.
The TOWER study is the confirmatory trial for BLINCYTO.
Click here to read about the trial on
ClinicalTrials.gov.
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 tyrosine kinase
inhibitor (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,
relapsed free survival, OS and adverse events.
Safety results among subjects who received BLINCYTO were
comparable to those seen in the Phase 2 studies in adult patients
with Ph- relapsed or refractory B-cell precursor ALL.
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, 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 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
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. 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.
Discovery or identification of new product candidates cannot be
guaranteed and movement from concept to product is uncertain;
consequently, there can be no guarantee that any particular product
candidate will be successful and become a commercial product.
Further, some raw materials, medical devices and component parts
for our products are supplied by sole third-party suppliers.
Certain of our distributors, customers and payers have substantial
purchasing leverage in their dealings with us. 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.
The scientific information discussed in this news release
relating to new indications for our products is preliminary and
investigative and is not part of the labeling approved by the U.S.
Food and Drug Administration for the products. The products are not
approved for the investigational use(s) discussed in this news
release, and no conclusions can or should be drawn regarding the
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. Acute lymphoblastic leukaemia risks and
causes.
http://www.cancerresearchuk.org/about-cancer/type/all/about/acute-lymphoblastic-leukaemia-risks-and-causes.
Accessed Jan. 13, 2017.
- Mayo Clinic. Acute lymphocytic leukemia.
http://www.mayoclinic.com/health/acute-lymphocytic-leukemia/DS00558.
Accessed Jan. 13, 2017.
- Davis T, Farag SS. Treating relapsed or refractory Philadelphia chromosome-negative acute
lymphoblastic leukemia: liposome-encapsulated vincristine. Int J
Nanomedicine. 2013:8 3479-3488.
- Katz AJ, et al. Acute lymphoblastic leukemia: an assessment of
international incidence, survival, and disease burden. Cancer
Causes Control. 2015;26(11):1627-42.
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