THOUSAND OAKS,
Calif., June 21,
2017 /PRNewswire/ -- Amgen (NASDAQ: AMGN)
today announced that new clinical data and analyses from its
hematology portfolio will be presented at the 22nd
Congress of the European Hematology
Association (EHA) in Madrid, June 22-25, 2017. Key
data will be presented from studies evaluating KYPROLIS®
(carfilzomib), BLINCYTO® (blinatumomab),
XGEVA® (denosumab) and Nplate®
(romiplostim).
"Helping patients live longer is the ultimate goal of all
of our oncology therapeutic research and development," said
Sean E. Harper, M.D., executive vice
president of Research and Development at Amgen. "The KYPROLIS and
BLINCYTO overall survival data at EHA are impressive and give us
confidence that we are making significant progress finding
effective new therapies for these difficult-to-treat
cancers."
KYPROLIS® is the first-and-only multiple
myeloma therapy to demonstrate superior overall survival in a
head-to-head comparison with a current standard of care, extending
survival by 7.6 months over Velcade®
(bortezomib).1 These results from the ENDEAVOR trial
will be featured in an oral presentation at EHA.
- Overall Survival of Patients With Relapsed or
Refractory Multiple Myeloma Treated With Carfilzomib and
Dexamethasone Versus Bortezomib and Dexamethasone in the Randomized
Phase 3 ENDEAVOR Trial
Abstract #S458, Oral
Presentation, Saturday, June 24 at
4:30 p.m. CET in Feria de
Madrid, Hall A
- Updated Results From ASPIRE and ENDEAVOR, Randomised,
Open-Label, Multicentre Phase 3 Studies Of Carfilzomib in Patients
With Relapsed/Refractory Multiple Myeloma
(RRMM)
Abstract #P333, Poster Presentation,
Friday, June 23 at 5:15 p.m. CET in Feria de Madrid, Poster Area (Hall 7)
A new analysis will be presented from the Phase 3 TOWER
study, which demonstrated that in adult patients treated with no
prior salvage therapy, BLINCYTO more than doubled median overall
survival compared to standard of care chemotherapy in Philadelphia chromosome-negative (Ph-)
relapsed or refractory B-cell precursor acute lymphoblastic
leukemia (ALL). These data come from a subgroup analysis, and TOWER
was not powered to assess overall survival efficacy in this
subgroup.
- Blinatumomab Versus SOC Chemotherapy in First Salvage
Compared With Second or Greater Salvage in a Phase 3
Study
Abstract #S478, Oral Presentation,
Saturday, June 24 at 4:30 p.m. CET in Feria de Madrid, Hall E
- Exposure-Adjusted Adverse Events Comparing
Blinatumomab With Standard of Care Chemotherapy in Adults With
Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia From a
Randomized Phase 3 Study
Abstract #P524, Poster
Presentation, Saturday, June 24 at
5:30 p.m. CET in Feria de
Madrid, Poster Area (Hall
7)
- Blinatumomab Use in Pediatric and Adolescent Patients
With Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia
From an Open-Label, Multicenter, Expanded Access
Study
Abstract #P521, Poster Presentation,
Saturday, June 24 at 5:30 p.m. CET in Feria de Madrid, Poster Area (Hall 7)
New XGEVA data will be presented during an oral session,
highlighting results from a post-hoc, 15-month landmark analysis of
the Phase 3 '482 study, the largest international multiple myeloma
trial ever conducted. This analysis demonstrated an improved delay
in time to first skeletal-related event for the XGEVA treated
patients. The study endpoint and the analysis were not powered to
determine efficacy.
- Comparison of Denosumab (DMB) With Zoledronic Acid
(ZA) for the Treatment of Bone Disease in Patients (Pts) With Newly
Diagnosed Multiple Myeloma; an International, Randomized, Double
Blind Trial
Abstract #S782, Oral Presentation,
Sunday, June 25 at 8:45 a.m. CET in Feria de Madrid, Hall D
On June 16, the U.S. Food
and Drug Administration (FDA) accepted for review the XGEVA
supplemental Biologics License Application that seeks to expand the
currently approved indication for the prevention of
skeletal-related events in patients with bone metastases from solid
tumors to include patients with multiple myeloma. The Prescription
Drug User Fee Act (PDUFA) target action date is Feb. 3, 2018. Data from the '482 study are also
the basis of an application for a variation to the marketing
authorization submitted to the European Medicines Agency.
Currently, XGEVA is not indicated for the prevention of
skeletal-related events in patients with multiple
myeloma.
The Nplate abstracts to be presented at EHA include data
from an ongoing, open-label extension study evaluating the safety
and efficacy of Nplate in children with immune thrombocytopenia
(ITP):
- Safety and Efficacy of Long-Term Open-Label Dosing of
Subcutaneous (Sc) Romiplostim in Children With Immune
Thrombocytopenia (ITP)
Abstract #P727, Poster
Presentation, Saturday, June 24 at
5:30 p.m. CET in Feria de
Madrid, Poster Area (Hall
7)
- A Single-Arm, Open-Label, Long-Term Efficacy and
Safety Study of Subcutaneous (Sc) Romiplostim in Children With
Immune Thrombocytopenia (ITP)
Abstract #P367,
Poster Presentation, Friday, June 23
at 5:15 p.m. CET in Feria de
Madrid, Poster Area (Hall
7)
Abstracts are currently available on the EHA
website.
About
KYPROLIS® (carfilzomib)
Proteasomes
play an important role in cell function and growth by breaking down
proteins that are damaged or no longer
needed.2 KYPROLIS has been shown to
block proteasomes, leading to an excessive build-up of proteins
within cells.2 In some cells, KYPROLIS
can cause cell death, especially in myeloma cells because they are
more likely to contain a higher amount of abnormal
proteins.2,3
KYPROLIS is approved in the U.S. for the
following:
- In combination with dexamethasone or with lenalidomide
plus dexamethasone for the treatment of patients with relapsed or
refractory multiple myeloma who have received one to three lines of
therapy.
- As a single agent for the treatment of patients with
relapsed or refractory multiple myeloma who have received one or
more lines of therapy.
KYPROLIS is also approved in Argentina, Australia, Bahrain, Canada, Hong
Kong, Israel, Japan, Kuwait, Lebanon, Macao, Mexico, Thailand, Colombia, S. Korea, Canada, Qatar, Switzerland, United
Arab Emirates, Turkey,
Russia, Brazil, India
and the European Union. Additional regulatory applications for
KYPROLIS are underway and have been submitted to health authorities
worldwide.
For more U.S. information, please
visit www.kyprolis.com.
Important EU Product Safety Information
This medicinal product is subject to additional
monitoring. This will allow quick identification of new safety
information. Healthcare professionals are asked to report any
suspected adverse reactions.
Kyprolis treatment should be supervised by a physician
experienced in the use of anti-cancer therapy. The most serious
side effects that may occur during Kyprolis treatment include:
Cardiac toxicity, pulmonary toxicities, pulmonary hypertension,
dyspnea, hypertension including hypertensive crises, acute renal
failure, tumor lysis syndrome, infusion reactions,
thrombocytopenia, hepatic toxicity, posterior reversible
encephalopathy syndrome (PRES) and thrombotic thrombocytopenic
purpura/hemolytic uremic syndrome (TTP/HUS). The most common side
effects are anemia, fatigue, diarrhea, thrombocytopenia, nausea,
pyrexia, dyspnea, respiratory tract infection, cough and peripheral
edema.
Please refer to the Summary of Product Characteristics for
full European prescribing information.
Important U.S. Product Safety
Information
Cardiac Toxicities
- New onset or worsening of pre-existing cardiac failure
(e.g., congestive heart failure, pulmonary edema, decreased
ejection fraction), restrictive cardiomyopathy, myocardial
ischemia, and myocardial infarction including fatalities have
occurred following administration of KYPROLIS. Some events occurred
in patients with normal baseline ventricular function. Death due to
cardiac arrest has occurred within one day of KYPROLIS
administration.
- Monitor patients for clinical signs or symptoms of
cardiac failure or cardiac ischemia. Evaluate promptly if cardiac
toxicity is suspected. Withhold KYPROLIS for Grade 3 or 4 cardiac
adverse events until recovery, and consider whether to restart
KYPROLIS at 1 dose level reduction based on a benefit/risk
assessment.
- While adequate hydration is required prior to each dose
in Cycle 1, monitor all patients for evidence of volume overload,
especially patients at risk for cardiac failure. Adjust total fluid
intake as clinically appropriate in patients with baseline cardiac
failure or who are at risk for cardiac failure.
- Patients ≥ 75 years, the risk of cardiac failure is
increased. Patients with New York Heart Association Class III and
IV heart failure, recent myocardial infarction, conduction
abnormalities, angina, or arrhythmias may be at greater risk for
cardiac complications and should have a comprehensive medical
assessment (including blood pressure and fluid management) prior to
starting treatment with KYPROLIS and remain under close
follow-up.
Acute Renal Failure
- Cases of acute renal failure and renal insufficiency
adverse events (including renal failure) have occurred in patients
receiving KYPROLIS. Acute renal failure was reported more
frequently in patients with advanced relapsed and refractory
multiple myeloma who received KYPROLIS monotherapy. Monitor renal
function with regular measurement of the serum creatinine and/or
estimated creatinine clearance. Reduce or withhold dose as
appropriate.
Tumor Lysis Syndrome
- Cases of Tumor Lysis Syndrome (TLS), including fatal
outcomes, have occurred in patients receiving KYPROLIS. Patients
with multiple myeloma and a high tumor burden should be considered
at greater risk for TLS. Adequate hydration is required prior to
each dose in Cycle 1, and in subsequent cycles as needed. Consider
uric acid lowering drugs in patients at risk for TLS. Monitor for
evidence of TLS during treatment and manage promptly. Withhold
KYPROLIS until TLS is resolved.
Pulmonary Toxicity
- Acute Respiratory Distress Syndrome (ARDS), acute
respiratory failure, and acute diffuse infiltrative pulmonary
disease such as pneumonitis and interstitial lung disease have
occurred in patients receiving KYPROLIS. Some events have been
fatal. In the event of drug-induced pulmonary toxicity, discontinue
KYPROLIS.
Pulmonary Hypertension
- Pulmonary arterial hypertension (PAH) was reported in
patients treated with KYPROLIS. Evaluate with cardiac imaging
and/or other tests as indicated. Withhold KYPROLIS for PAH until
resolved or returned to baseline and consider whether to restart
KYPROLIS based on a benefit/risk assessment.
Dyspnea
- Dyspnea was reported in patients treated with KYPROLIS.
Evaluate dyspnea to exclude cardiopulmonary conditions including
cardiac failure and pulmonary syndromes. Stop KYPROLIS for Grade 3
or 4 dyspnea until resolved or returned to baseline. Consider
whether to restart KYPROLIS based on a benefit/risk
assessment.
Hypertension
- Hypertension, including hypertensive crisis and
hypertensive emergency, has been observed with KYPROLIS. Some of
these events have been fatal. Monitor blood pressure regularly in
all patients. If hypertension cannot be adequately controlled,
withhold KYPROLIS and evaluate. Consider whether to restart
KYPROLIS based on a benefit/risk assessment.
Venous Thrombosis
- Venous thromboembolic events (including deep venous
thrombosis and pulmonary embolism) have been observed with
KYPROLIS. Thromboprophylaxis is recommended for patients being
treated with the combination of KYPROLIS with dexamethasone or with
lenalidomide plus dexamethasone. The thromboprophylaxis regimen
should be based on an assessment of the patient's underlying
risks.
- Patients using oral contraceptives or a hormonal method
of contraception associated with a risk of thrombosis should
consider an alternative method of effective contraception during
treatment with KYPROLIS in combination with dexamethasone or
lenalidomide plus dexamethasone.
Infusion Reactions
- Infusion reactions, including life-threatening reactions,
have occurred in patients receiving KYPROLIS.
- Symptoms include fever, chills, arthralgia, myalgia,
facial flushing, facial edema, vomiting, weakness, shortness of
breath, hypotension, syncope, chest tightness, or angina. These
reactions can occur immediately following or up to 24 hours after
administration of KYPROLIS. Premedicate with dexamethasone to
reduce the incidence and severity of infusion reactions. Inform
patients of the risk and of symptoms of an infusion reaction and to
contact a physician immediately if they occur.
Hemorrhage
- Fatal or serious cases of hemorrhage have been reported
in patients receiving KYPROLIS. Hemorrhagic events have included
gastrointestinal, pulmonary, and intracranial hemorrhage and
epistaxis. Promptly evaluate signs and symptoms of blood loss.
Reduce or withhold dose as appropriate.
Thrombocytopenia
- KYPROLIS causes thrombocytopenia with recovery to
baseline platelet count usually by the start of the next cycle.
Thrombocytopenia was reported in patients receiving KYPROLIS.
Monitor platelet counts frequently during treatment with KYPROLIS.
Reduce or withhold dose as appropriate.
Hepatic Toxicity
and Hepatic
Failure
- Cases of hepatic failure, including fatal cases, have
been reported during treatment with KYPROLIS. KYPROLIS can cause
increased serum transaminases. Monitor liver enzymes regularly
regardless of baseline values. Reduce or withhold dose as
appropriate.
Thrombotic Microangiopathy
- Cases of thrombotic microangiopathy, including thrombotic
thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS),
including fatal outcome have occurred in patients receiving
KYPROLIS. Monitor for signs and symptoms of TTP/HUS. Discontinue
KYPROLIS if diagnosis is suspected. If the diagnosis of TTP/HUS is
excluded, KYPROLIS may be restarted. The safety of reinitiating
KYPROLIS therapy in patients previously experiencing TTP/HUS is not
known.
Posterior Reversible Encephalopathy Syndrome
(PRES)
- Cases of PRES have occurred in patients receiving
KYPROLIS. PRES was formerly known as Reversible Posterior
Leukoencephalopathy Syndrome. Consider a neuro-radiological imaging
(MRI) for onset of visual or neurological symptoms. Discontinue
KYPROLIS if PRES is suspected and evaluate. The safety of
reinitiating KYPROLIS therapy in patients previously experiencing
PRES is not known.
Increased Fatal and Serious Toxicities in Combination
with Melphalan and Prednisone in Newly Diagnosed
Transplant‐ineligible
Patients
- In a clinical trial of
transplant‐ineligible patients with newly
diagnosed multiple myeloma comparing KYPROLIS, melphalan, and
prednisone (KMP) vs bortezomib, melphalan, and prednisone (VMP), a
higher incidence of serious and fatal adverse events was observed
in patients in the KMP arm. KYPROLIS in combination with melphalan
and prednisone is not indicated for
transplant‐ineligible patients with newly
diagnosed multiple myeloma.
Embryo-fetal Toxicity
- KYPROLIS can cause fetal harm when administered to a
pregnant woman based on its mechanism of action and findings in
animals.
- Females of reproductive potential should be advised to
avoid becoming pregnant while being treated with KYPROLIS. Males of
reproductive potential should be advised to avoid fathering a child
while being treated with KYPROLIS. If this drug is used during
pregnancy, or if pregnancy occurs while taking this drug, the
patient should be apprised of the potential hazard to the
fetus.
ADVERSE REACTIONS
- The most common adverse reactions occurring in at least
20% of patients treated with KYPROLIS in the combination therapy
trials: anemia, neutropenia, diarrhea, dyspnea, fatigue,
thrombocytopenia, pyrexia, insomnia, muscle spasm, cough, upper
respiratory tract infection, hypokalemia.
- The most common adverse reactions occurring in at least
20% of patients treated with KYPROLIS in monotherapy trials:
anemia, fatigue, thrombocytopenia, nausea, pyrexia, dyspnea,
diarrhea, headache, cough, edema peripheral.
Please see full prescribing information
at www.kyprolis.com.
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 European
Union for the treatment of adults with Ph- relapsed or refractory
B-cell precursor ALL.
Important EU BLINCYTO®
(blinatumomab) Safety Information
This product is subject to additional monitoring in the
EU. All suspected adverse reactions should be reported in
accordance with the national reporting system.
The adverse reactions described in this section were
identified in the pivotal clinical study (N=189).The most serious
adverse reactions that may occur during blinatumomab treatment
include: infections (31.7%), neurologic events (16.4%),
neutropenia/febrile neutropenia (15.3%), cytokine release syndrome
(0.5%), and tumor lysis syndrome (0.5%). The most common adverse
reactions were: infusion-related reactions (67.2%), infections
(63.0%), pyrexia (59.8%), headache (34.4%), febrile neutropenia
(28%), peripheral edema (25.9%), nausea (24.3%), hypokalaemia
(23.8%), constipation (20.6%), anaemia (20.1%), cough (18.5%),
diarrhea (18.0%), tremor (17.5%), neutropenia (17.5%), abdominal
pain (16.9%), insomnia (15.3%), fatigue (15.3%), and chills
(15.3%).
Please refer to the Summary of Product Characteristics
for full European prescribing 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®.
- Risk of Serious Adverse Reactions in Pediatric Patients
due to Benzyl Alcohol Preservative: Serious and fatal adverse
reactions including "gasping syndrome," which is characterized by
central nervous syndrome depression, metabolic acidosis, and
gasping respirations, can occur in neonates and infants treated
with benzyl alcohol-preserved drugs including BLINCYTO®
(with preservative). When prescribing BLINCYTO® (with
preservative) for pediatric patients, consider combined daily
metabolic load of benzyl alcohol from all sources including
BLINCYTO® (with preservative) and other drugs containing
benzyl alcohol, as the minimum amount of benzyl alcohol at which
serious adverse reactions may occur is not known. Due to the
addition of bacteriostatic saline, 7-day bags of
BLINCYTO® solution for infusion with preservative
contain benzyl alcohol and are not recommended for use in any
patients weighing < 22kg.
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
XGEVA® (denosumab)
XGEVA
targets the RANK Ligand pathway to prevent the formation, function
and survival of osteoclasts, which break down bone. XGEVA is
indicated for the prevention of skeletal-related events in patients
with bone metastases from solid tumors and for treatment of adults
and skeletally mature adolescents with giant cell tumor of bone
that is unresectable or where surgical resection is likely to
result in severe morbidity. XGEVA is also indicated in the U.S. for
the treatment of hypercalcemia of malignancy refractory to
bisphosphonate therapy. XGEVA is not indicated for the prevention
of skeletal-related events in patients with multiple
myeloma.
Important EU Product Safety Information
Special Warnings and
Precautions: Pre-existing hypocalcaemia must
be corrected prior to initiating therapy with XGEVA. Hypocalcaemia
can occur at any time during therapy. Monitor calcium prior to
initial dose, within two weeks of initial dose and if suspected
symptoms of hypocalcaemia occur. Severe symptomatic hypocalcaemia
has been reported. Consider additional monitoring of calcium level
in patients with risk factors for hypocalcaemia or if otherwise
indicated based on clinical condition of the patient. If
hypocalcaemia occurs while receiving XGEVA, additional calcium
supplementation and additional monitoring may be
necessary.
Patients with severe renal impairment (creatinine
clearance < 30ml/min) or receiving dialysis are at greater risk
of developing hypocalcaemia; this risk and accompanying elevations
in parathyroid hormone increases with increasing degree of renal
impairment. Regular monitoring of calcium levels in these patients
is especially important.
Osteonecrosis of the jaw (ONJ) has occurred commonly in
patients treated with XGEVA. Delay treatment in patients with
unhealed open soft tissue lesions in the mouth. A dental
examination with preventive dentistry and an individual
benefit-risk assessment is recommended prior to treatment. Refer to
the SmPC for risk factors for ONJ. Patients should be
encouraged to maintain good oral hygiene, receive routine dental
check-ups and immediately report oral symptoms during treatment
with XGEVA. While on treatment, invasive dental procedures should
be performed only after careful consideration and avoided in close
proximity to XGEVA administration. The management plan of patients
who develop ONJ should be set up in close collaboration between the
treating physician and a dentist or oral surgeon with expertise in
ONJ.
Atypical femoral fracture (AFF) has been reported in
patients receiving XGEVA. Discontinuation of XGEVA therapy in
patients suspected to have AFF should be considered pending
evaluation of the patient based on an individual benefit risk
assessment. XGEVA is not recommended in patients with growing
skeletons. Clinically significant hypercalcaemia has been reported
in XGEVA-treated patients with growing skeletons weeks to months
following treatment discontinuation. Patients being treated with
XGEVA should not be treated concomitantly with other denosumab
containing medicinal products (for osteoporosis indications) or
with bisphosphonates. Patients with rare hereditary problems of
fructose intolerance should not use XGEVA.
Adverse reactions in patients receiving XGEVA to prevent
the occurrence of skeletal related events: very common (≥ 1/10)
dyspnea, diarrhea and musculoskeletal pain; common (≥ 1/100 to <
1/10) hypocalcaemia, hypophosphatemia, tooth extraction,
hyperhidrosis and osteonecrosis of the jaw; rare (≥ 1/10,000 to
< 1/1000) drug hypersensitivity, anaphylactic reaction, atypical
femoral fracture. In three phase III clinical trials, ONJ was
confirmed in 1.8% of patients treated with XGEVA and 1.3% of
patients treated with zoledronic acid (primary treatment phase).
Among subjects with confirmed ONJ, most (81% in both treatment
groups) had a history of tooth extraction, poor oral hygiene,
and/or use of a dental appliance. Hypocalcaemia was reported in
9.6% of patients treated with XGEVA and 5.0% of patients treated
with zoledronic acid. Neutralizing antibodies have not been
observed in clinical studies. In the postmarketing setting,
severe symptomatic hypocalcaemia (including fatal cases),
hypersensitivity (including rare events of anaphylactic reaction)
and musculoskeletal pain (including severe cases) have been
reported. Please consult the SmPC for a full description
of undesirable effects.
Contraindications: Severe,
untreated hypocalcaemia; hypersensitivity to the active substance
or to any of the excipients; unhealed lesions from dental or oral
surgery.
U.S. Important Safety Information
Hypocalcemia
Pre-existing
hypocalcemia must be corrected prior to initiating therapy with
XGEVA®. XGEVA® can cause severe symptomatic
hypocalcemia, and fatal cases have been reported. Monitor calcium
levels, especially in the first weeks of initiating therapy, and
administer calcium, magnesium, and vitamin D as necessary. Monitor
levels more frequently when XGEVA® is administered with
other drugs that can also lower calcium levels. Advise patients to
contact a healthcare professional for symptoms of
hypocalcemia.
An increased risk of hypocalcemia has been observed in
clinical trials of patients with increasing renal dysfunction, most
commonly with severe dysfunction (creatinine clearance less than 30
mL/minute and/or on dialysis), and with inadequate/no calcium
supplementation. Monitor calcium levels and calcium and vitamin D
intake.
Hypersensitivity
XGEVA®
is contraindicated in patients with known clinically significant
hypersensitivity to XGEVA®, including anaphylaxis that
has been reported with use of XGEVA®. Reactions may
include hypotension, dyspnea, upper airway edema, lip swelling,
rash, pruritus, and urticaria. If an anaphylactic or other
clinically significant allergic reaction occurs, initiate
appropriate therapy and discontinue XGEVA® therapy
permanently.
Drug Products with Same Active
Ingredient
Patients receiving XGEVA®
should not take Prolia® (denosumab).
Osteonecrosis of the Jaw
Osteonecrosis of the jaw (ONJ) has been reported in patients
receiving XGEVA®, manifesting as jaw pain,
osteomyelitis, osteitis, bone erosion, tooth or periodontal
infection, toothache, gingival ulceration, or gingival erosion.
Persistent pain or slow healing of the mouth or jaw after dental
surgery may also be manifestations of ONJ. In clinical trials in
patients with osseous metastasis, the incidence of ONJ was
higher with longer duration of exposure.
Patients with a history of tooth extraction, poor oral
hygiene, or use of a dental appliance are at a greater risk to
develop ONJ. Other risk factors for the development of ONJ include
immunosuppressive therapy, treatment with angiogenesis inhibitors,
systemic corticosteroids, diabetes, and gingival
infections.
Perform an oral examination and appropriate preventive
dentistry prior to the initiation of XGEVA® and
periodically during XGEVA® therapy. Advise patients
regarding oral hygiene practices. Avoid invasive dental procedures
during treatment with XGEVA®. Consider temporarily
interrupting XGEVA® therapy if an invasive dental
procedure must be performed.
Patients who are suspected of having or who develop ONJ
while on XGEVA® should receive care by a dentist or an
oral surgeon. In these patients, extensive dental surgery to treat
ONJ may exacerbate the condition.
Atypical Subtrochanteric and Diaphyseal Femoral
Fracture
Atypical femoral fracture has been
reported with XGEVA®. These fractures can occur anywhere
in the femoral shaft from just below the lesser trochanter to above
the supracondylar flare and are transverse or short oblique in
orientation without evidence of comminution.
Atypical femoral fractures most commonly occur with
minimal or no trauma to the affected area. They may be bilateral
and many patients report prodromal pain in the affected area,
usually presenting as dull, aching thigh pain, weeks to months
before a complete fracture occurs. A number of reports note that
patients were also receiving treatment with glucocorticoids (e.g.
prednisone) at the time of fracture. During XGEVA®
treatment, patients should be advised to report new or unusual
thigh, hip, or groin pain. Any patient who presents with thigh or
groin pain should be suspected of having an atypical fracture and
should be evaluated to rule out an incomplete femur fracture.
Patients presenting with an atypical femur fracture should also be
assessed for symptoms and signs of fracture in the contralateral
limb. Interruption of XGEVA® therapy should be
considered, pending a risk/benefit assessment, on an individual
basis.
Hypercalcemia Following Treatment Discontinuation in
Patients with Growing Skeletons
Clinically
significant hypercalcemia has been reported in XGEVA®
treated patients with growing skeletons, weeks to months following
treatment discontinuation. Monitor patients for signs and symptoms
of hypercalcemia and treat appropriately.
Embryo-Fetal Toxicity
XGEVA® can cause fetal harm when administered to a
pregnant woman. Based on findings in animals, XGEVA® is
expected to result in adverse reproductive effects. Advise females
of reproductive potential to use highly effective contraception
during therapy, and for at least 5 months after the last dose of
XGEVA®. Apprise the patient of the potential hazard to a
fetus if XGEVA® is used during pregnancy or if the
patient becomes pregnant while patients are exposed to
XGEVA®.
Adverse Reactions
The most common
adverse reactions in patients receiving XGEVA® with bone
metastasis from solid tumors were fatigue/asthenia,
hypophosphatemia, and nausea. The most common serious adverse
reaction was dyspnea.
The most common adverse reactions resulting in
discontinuation were osteonecrosis and hypocalcemia. The most
common adverse reactions in patients receiving XGEVA®
for giant cell tumor of bone were arthralgia, headache, nausea,
back pain, fatigue, and pain in extremity. The most common serious
adverse reactions were osteonecrosis of the jaw and osteomyelitis.
The most common adverse reactions resulting in discontinuation of
XGEVA® were osteonecrosis of the jaw and tooth abscess
or tooth infection. The most common adverse reactions in
patients receiving XGEVA® for hypercalcemia of
malignancy were nausea, dyspnea, decreased appetite, headache,
peripheral edema, vomiting, anemia, constipation, and
diarrhea.
Denosumab is also marketed as Prolia® in
other indications.
Please
visit www.amgen.com or www.xgeva.com for
Full U.S. Prescribing Information.
About Nplate® (romiplostim)
Nplate is approved in over 50 countries worldwide, including
the U.S., European Union (EU), Canada, Australia, Russia, Mexico, Switzerland, Lichtenstein, Japan, Argentina, Israel, South
Korea, Hong Kong, and
Chile. Nplate also has received
orphan designation for chronic ITP in the U.S. (2003), the EU
(2005) and other parts of the world.
Nplate is the first FDA-approved treatment specifically
for adult chronic ITP.
In the U.S., Nplate is indicated for the treatment of
thrombocytopenia in patients with chronic ITP who have had an
insufficient response to corticosteroids, immunoglobulins or
splenectomy. Nplate is not indicated for the treatment of
thrombocytopenia due to myelodysplastic syndrome (MDS) or any cause
of thrombocytopenia other than chronic ITP. Nplate should be used
only in patients with ITP whose degree of thrombocytopenia and
clinical condition increase the risk for bleeding. Nplate should
not be used in an attempt to normalize platelet counts.
In the EU, Nplate is indicated for adult chronic-immune
(idiopathic)-thrombocytopenic-purpura (ITP) patients who are
refractory to other treatments (e.g. corticosteroids,
immunoglobulins).
Nplate was named as a recipient of the U.S. Prix Galien
2009 "Best Biotechnology Product" award and also received the 2009
Scrip Awards for "Best New Drug." Nplate has also been honored with
numerous awards throughout the EU, including a 2010 Prix Galien in
France in the category of "Drugs
for Rare Diseases," and the 2011 Prix Galien in Germany in the category of "Specialist Care."
In September 2010, Nplate was awarded
the 2010 International Prix Galien Award, an award granted every
two years which recognizes the "best of the best" selected from
previous national Prix Galien award
recipients.
For more information about Nplate, please visit
www.Nplate.com.
Important EU Nplate® Safety
Information
The EU Summary of Product
Characteristics for Nplate lists the following Special Warnings and
Precautions: Reoccurrence of thrombocytopenia and
bleeding after cessation of treatment, increased bone marrow
reticulin, thrombotic/thromboembolic complications, progression of
existing MDS (in patients with MDS), medication errors, loss of
response to Nplate, and effects on red and white blood
cells.
The most common adverse reactions observed include
hypersensitivity reactions (including cases of rash, urticarial and
angioedema) and headache. As with all therapeutic proteins, there
is a potential for immunogenicity.
Please refer to the Summary of Product Characteristics
for full European prescribing information.
Important U.S. Nplate® Safety
Information
Risk of Progression of Myelodysplastic Syndromes to
Acute Myelogenous Leukemia
- In Nplate® clinical trials of patients with
myelodysplastic syndromes (MDS) and severe thrombocytopenia,
progression from MDS to acute myelogenous leukemia (AML) has been
observed.
- Nplate® is not indicated for the treatment of
thrombocytopenia due to MDS or any cause of thrombocytopenia other
than chronic ITP.
Thrombotic/Thromboembolic Complications
- Thrombotic/thromboembolic complications may result from
increases in platelet counts with Nplate® use. Portal
vein thrombosis has been reported in patients with chronic liver
disease receiving Nplate®.
- To minimize the risk for thrombotic/thromboembolic
complications, do not use Nplate® in an attempt to
normalize platelet counts. Follow the dose adjustment guidelines to
achieve and maintain a platelet count of ≥ 50 x 109/L.
Loss of Response to Nplate®
- Hyporesponsiveness or failure to maintain a platelet
response with Nplate® should prompt a search for
causative factors, including neutralizing antibodies to
Nplate®.
- To detect antibody formation, submit blood samples to
Amgen (1-800-772-6436). Amgen will assay these samples for
antibodies to Nplate® and thrombopoietin
(TPO).
- Discontinue Nplate® if the platelet count does
not increase to a level sufficient to avoid clinically important
bleeding after 4 weeks at the highest weekly dose of 10
mcg/kg.
Laboratory Monitoring
- Obtain CBCs, including platelet counts, weekly during the
dose adjustment phase of Nplate® therapy and then
monthly following establishment of a stable Nplate®
dose.
- Obtain CBCs, including platelet counts, weekly for at
least two weeks following discontinuation of
Nplate®.
Adverse Reactions
- In the placebo-controlled trials, headache was the most
commonly reported adverse drug reaction, occurring in 35% of
patients receiving Nplate® and 32% of patients receiving
placebo. Headaches were usually of mild or moderate
severity.
- Most common adverse reactions (≥ 5% higher patient
incidence in Nplate® versus placebo) were Arthralgia
(26%, 20%), Dizziness (17%, 0%), Insomnia (16%, 7%), Myalgia (14%,
2%), Pain in Extremity (13%, 5%) , Abdominal Pain (11%, 0%),
Shoulder Pain (8%, 0%), Dyspepsia (7%, 0%), and Paresthesia (6%,
0%).
- Nplate® administration may increase the risk
for development or progression of reticulin fiber formation within
the bone marrow. This formation may improve upon discontinuation of
Nplate®. In a clinical trial, one patient with ITP and
hemolytic anemia developed marrow fibrosis with collagen during
Nplate® therapy.
Please see full U.S. Prescribing Information and
Medication Guide at
www.Nplate.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. 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. 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:
- Dimopoulos MA, Goldschmidt H, Niesvisky R, et al.
Overall Survival of Patients with Relapsed or Refractory
Multiple Myeloma Treated with Carfilzomib and Dexamethasone versus
Bortezomib and Dexamethasone in the Randomized Phase 3 ENDEAVOR
Trial. Abstract presented at: 16th International Myeloma Workshop;
March 1-4, 2017; New Delhi, India. Abstract.
- Moreau P, Richardson PG, Cavo M, et al.
Proteasome Inhibitors in Multiple Myeloma: 10 Years Later.
Blood. 2012; 120(5):947-959.
- Kortuem KM and Stewart AK. Carfilzomib.
Blood. 2012; 121(6):893-897.
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SOURCE Amgen