New Data To Be Presented At ASH 2017 Underscore Amgen's Commitment To Improving Lives And Changing Outcomes For Patients With Difficult-To-Treat Blood Cancers
THOUSAND OAKS, Calif., Dec. 7, 2017 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced that new clinical data and analyses from 33 abstracts, including six oral presentations, evaluating approved medicines and investigational immuno-oncology agents from the Company's robust hematology portfolio and pipeline will be presented at the 59(th) American Society of Hematology (ASH) Annual Meeting & Exposition in Atlanta, Dec. 9-12, 2017.
The breadth and depth of data to be presented at ASH highlight Amgen's commitment to advancing treatment options for patients with some of the most difficult-to-treat blood cancers and disorders. Notably at ASH, positive overall survival (OS) results from the Phase 3 ASPIRE trial will be detailed for the first time in an oral presentation, which showed the addition of KYPROLIS(®) (carfilzomib) to lenalidomide and dexamethasone (KRd) significantly extended OS versus lenalidomide and dexamethasone (Rd) alone in patients with relapsed or refractory multiple myeloma. The safety data from ASPIRE was consistent with the known safety profile of KYPROLIS.
"At Amgen, we take great pride in our heritage and commitment to developing innovative, life-changing treatments for some of the toughest cancers," said David Reese, M.D., senior vice president of Translational Sciences and Oncology at Amgen. "The range of data from our broad portfolio of treatments and innovative pipeline assets together demonstrate the considerable potential of Amgen's investment in oncology and blood cancers. Results being presented at ASH also highlight the potential of BiTEs, our bispecific T cell engager molecules, to activate a patient's immune system to fight cancer, and demonstrate the benefit our approved medicines can provide for patients with blood cancers across the disease continuum."
Translating Research into Improved Survival for Patients
New results to be presented at ASH demonstrate how two Amgen medicines - KYPROLIS and BLINCYTO(®) (blinatumomab) - improved OS in adult patients with relapsed multiple myeloma and Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL), respectively.
KYPROLIS-based regimens (KRd) and KYPROLIS(®) and dexamethasone (Kd) are the first and only to demonstrate improved OS over two standards of care (Rd) and Velcade(®) (bortezomib) and dexamethasone (Vd) in two Phase 3 trials in relapsed or refractory patients with multiple myeloma. In addition to ASPIRE, OS data from the Phase 3 ENDEAVOR trial will be detailed in presentations, which showed how Kd were superior in improving OS versus Vd across subgroups of relapsed or refractory patients with multiple myeloma.
BLINCYTO is the first-and-only approved CD19-directed CD3 BiTE(®) immunotherapy and the only treatment to demonstrate a statistically significant improvement inOS in patients with relapsed or refractory ALL. Results from an exploratory analysis evaluating the OS benefit of BLINCYTO maintenance therapy in patients with Ph- relapsed or refractory B-cell precursor ALL will be highlighted during a poster session. BLINCYTO maintenance therapy reduced the risk of death by 41 percent versus no maintenance therapy. Adverse events were consistent with the established safety profile in adult patients with Ph- relapsed or refractory B-cell precursor ALL. Overall safety event rates were lower in maintenance vs. induction or consolidation cycles.
The U.S. Food and Drug Administration (FDA) has accepted for priority review the supplemental Biologics License Application (sBLA) for BLINCYTO for the treatment of patients with frontline or relapsed B-cell precursor ALL with minimal residual disease (MRD), the first application to be submitted for this indication. The Prescription Drug User Fee Act (PDUFA) target action date is March 29, 2018. Results from the Phase 2 BLAST study upon which the sBLA is based were presented at the 57(th) Annual ASH Meeting and Exposition in 2015.
Advancing Outcomes Across the Disease Continuum
New real-world data in patients with multiple myeloma bone disease will also be presented. Of note, a study evaluating patterns and predictors of initiation of intravenous bisphosphonates among multiple myeloma patients will be highlighted in an oral session. In the study, less than half of patients initiated bisphosphonate treatment in the two years after diagnosis to prevent fractures and other skeletal-related events, underscoring the need to manage the bone health of patients with myeloma more proactively.
Spotlighting Robust Amgen Immuno-Oncology Pipeline
An array of data from the Amgen oncology pipeline will be presented at ASH, spanning a variety of modalities across immuno-oncology. Notably, four presentations will focus on the potential of Amgen's BiTE(®) platform as a novel immuno-oncology approach to treating a variety of hematologic cancers. Amgen is the only company with an approved BiTE(®) (BLINCYTO) and believes that this technology platform holds significant potential in other hematologic cancers and in solid tumors.
Amgen Investor Webcast
Amgen will host a webcast investor meeting at ASH on Saturday, Dec. 9, 2017, at 11:30 a.m. ET. David M. Reese, M.D., senior vice president of Translational Sciences and Oncology at Amgen, together with other members of Amgen's management team and a clinical investigator, will participate to discuss the Company's oncology program, including Amgen's BiTE(®) immunotherapy platform.
Live audio of the investor meeting will be broadcast over the internet simultaneously and will be available to members of the news media, investors and the general public.
The webcast, as with other selected presentations regarding developments in Amgen's business given at certain investor and medical conferences, can be accessed on Amgen's website, www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen's Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.
Key Amgen presentation information for ASH 2017 is featured here. A complete listing of abstracts can be found on the ASH website.
Translating Research into Improved Survival for Patients
-- Overall Survival (OS) of Patients With Relapsed/Refractory Multiple
Myeloma (RRMM) Treated With Carfilzomib, Lenalidomide, and Dexamethasone
(KRd) Versus Lenalidomide and Dexamethasone (Rd): Final Analysis From
the Randomized Phase 3 ASPIRE TrialAbstract #743, Oral Presentation,
Monday, Dec. 11 at 2:45 p.m. ET in Georgia World Congress Center,
Building C, Level 1, Hall C1
-- Overall Survival of Relapsed/Refractory Multiple Myeloma Patients
Treated With Carfilzomib and Dexamethasone vs Bortezomib and
Dexamethasone: Results From the Phase 3 ENDEAVOR Study According to Age
SubgroupAbstract #1885, Poster Presentation, Saturday, Dec. 9 at 5:30
p.m. ET in Georgia World Congress Center, Building A, Level 1, Hall A2
-- Overall Survival of Patients With Relapsed Multiple Myeloma Treated With
Carfilzomib and Dexamethasone Versus Bortezomib and Dexamethasone
According to Prior Line of Therapy and Previous Exposure to Bortezomib:
Secondary Analysis of the Phase 3 ENDEAVOR StudyAbstract #1850, Poster
Presentation, Saturday, Dec. 9 at 5:30 p.m. ET in Georgia World Congress
Center, Building A, Level 1, Hall A2
-- Maintenance Therapy With Blinatumomab in Adults With Relapsed/Refractory
B-Precursor Acute Lymphoblastic Leukemia (ALL): Overall Survival in
Adults Enrolled In a Phase 3 Open-Label TrialAbstract #2552, Poster
Presentation, Sunday, Dec. 10 at 6 p.m. ET in Georgia World Congress
Center, Building A, Level 1, Hall A2
Advancing Outcomes Across the Disease Continuum
-- Patterns and Predictors of Initiation of Intravenous Bisphosphonates
Among Patients With Multiple Myeloma in the United StatesAbstract #534,
Oral Presentation, Sunday, Dec. 10 at 4:30 p.m. ET in Georgia World
Congress Center, Building B, Level 2, B206
-- Multiple Myeloma Patients and Risk of SRE - Real-World Evidence in US
Oncology ClinicsAbstract #2171, Poster Presentation, Saturday, Dec. 9 at
5:30 p.m. ET in Georgia World Congress Center, Building A, Level 1, Hall
A2
Spotlighting Robust Amgen Immuno-Oncology Pipeline
-- Preclinical Characterization of AMG 424, a Novel Humanized T
Cell-Recruiting Bispecific Anti-CD3/CD38 AntibodyAbstract #500, Oral
Presentation, Sunday, Dec. 10 at 4:30 p.m. ET in Georgia World Congress
Center, Building B, Level 3, B308-B309
-- CD33/CD3-Bispecific T-Cell Engaging (BiTE(®)) Antibody Constructs
Efficiently Target Monocytic CD14+HLA-DRlow IDO+AML-MDSCsAbstract #1363,
Poster Presentation, Saturday, Dec. 9 at 5:30 p.m. ET in Georgia World
Congress Center, Building A, Level 1, Hall A2
-- Evaluation of a FLT3 BiTE(®) for Acute Myeloid LeukemiaAbstract #1354,
Poster Presentation, Saturday, Dec. 9 at 5:30 p.m. ET in Georgia World
Congress Center, Building A, Level 1, Hall A2
-- Generation of a Half-life Extended Anti-CD19 BiTE(®) Antibody Construct
Compatible With Once-weekly Dosing for Treatment of CD19-positive
MalignanciesAbstract #2815, Poster Presentation, Sunday, Dec. 10 at 6
p.m. ET in Georgia World Congress Center, Building A, Level 1, Hall A2
-- AMG 592 is an Investigational IL-2 Mutein That Induces Highly Selective
Expansion of Regulatory T cellsAbstract #696, Oral Presentation, Monday,
Dec. 11 at 2:45 p.m. ET in Georgia World Congress Center, Building C,
Level 1, C108-C109
About KYPROLIS(®) (carfilzomib)
Proteasomes play an important role in cell function and growth by breaking down proteins that are damaged or no longer needed.(1) KYPROLIS has been shown to block proteasomes, leading to an excessive build-up of proteins within cells.(1) 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.(1,2)
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, Qatar, Switzerland, United Arab Emirates, Turkey, Russia, Brazil, India, Oman and the European Union. Additional regulatory applications for KYPROLIS are underway and have been submitted to health authorities worldwide.
IMPORTANT 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 relapsed or refractory B-cell precursor ALL in adults and children.
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. Additional regulatory applications for BLINCYTO are underway and have been submitted to health authorities worldwide.
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 bridge T cells to tumor cells, using the patient's own immune system to eradicate their cancer. 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
Indication and Important Safety Information, including Boxed WARNINGS, for BLINCYTO(® )(blinatumomab) for injection, for intravenous use
INDICATION
BLINCYTO(®) is indicated for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) in adults and children.
IMPORTANT SAFETY INFORMATION
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES
-- Cytokine Release Syndrome (CRS), which may be life-threatening or fatal,
occurred in patients receiving BLINCYTO®. Interrupt or discontinue
BLINCYTO® as recommended.
-- Neurological toxicities, which may be severe, life-threatening or fatal,
occurred in patients receiving BLINCYTO®. Interrupt or discontinue
BLINCYTO® as recommended.
Contraindications
BLINCYTO(®) is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.
Warnings and Precautions
-- Cytokine Release Syndrome (CRS): 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 65% of patients receiving
BLINCYTO(®) in clinical trials experienced neurological toxicities. The
median time to the first event was within the first 2 weeks of
BLINCYTO(®) treatment and the majority of events resolved. The most
common (>= 10%) manifestations of neurological toxicity were headache
and tremor. Severe, life-threatening, or fatal neurological toxicities
occurred in approximately 13% of patients, including encephalopathy,
convulsions, speech disorders, disturbances in consciousness, confusion
and disorientation, and coordination and balance disorders. 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 19 days. Grade 3 or greater elevations in liver enzymes
occurred in 7% 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 system
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. 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 < 22 kg.
Adverse Reactions
-- The most common adverse reactions in Philadelphia chromosome-negative
relapsed or refractory B-cell precursor ALL (TOWER Study) (>= 20%) in
the BLINCYTO(®) arm were infections (bacterial and pathogen
unspecified), pyrexia, headache, infusion-related reactions, anemia,
febrile neutropenia, thrombocytopenia, and neutropenia. Serious adverse
reactions were reported in 62% of patients. The most common serious
adverse reactions (>= 2%) included febrile neutropenia, pyrexia, sepsis,
pneumonia, overdose, septic shock, CRS, bacterial sepsis, device related
infection, and bacteremia.
-- Adverse reactions that were observed more frequently (>= 10%) in the
pediatric population compared to the adult population were pyrexia (80%
vs. 61%), hypertension (26% vs. 8%), anemia (41% vs. 24%),
infusion-related reaction (49% vs. 34%), thrombocytopenia (34% vs. 21%),
leukopenia (24% vs. 11%), and weight increased (17% vs. 6%).
-- In pediatric patients less than 2 years old (infants), the incidence of
neurologic toxicities was not significantly different than for the other
age groups, but its manifestations were different; the only event terms
reported were agitation, headache, insomnia, somnolence, and
irritability. Infants also had an increased incidence of hypokalemia
(50%) compared to other pediatric age cohorts (15-20%) or adults (17%).
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(®).
About XGEVA(®) (denosumab)
XGEVA targets the RANKL pathway to prevent the formation, function and survival of osteoclasts, which break down bone. As a monoclonal antibody, XGEVA is not cleared by the kidneys. XGEVA is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors. In the U.S., XGEVA currently has a limitation of use noting that it is not indicated for the prevention of skeletal-related events in patients with multiple myeloma. XGEVA is also indicated for the 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.
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 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.
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CONTACT: Amgen, Thousand Oaks
Kristen Davis, 805-447-3008 (Media)
Kristen Neese, 805-313-8267 (Media)
Arvind Sood, 805-447-1060 (Investors)
References
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