THOUSAND OAKS, Calif.,
Jan. 17, 2018 /PRNewswire/ -- Amgen
(NASDAQ:AMGN) today announced that the U.S. Food and Drug
Administration (FDA) has approved the supplemental New Drug
Application (sNDA) to add overall survival (OS) data from the Phase
3 head-to-head ENDEAVOR trial to the Prescribing Information for
KYPROLIS® (carfilzomib). Data added to the label
demonstrated that KYPROLIS and dexamethasone (Kd) reduced the risk
of death by 21 percent and increased OS by 7.6 months versus
Velcade® (bortezomib) and dexamethasone (Vd) in patients
with relapsed or refractory multiple myeloma (median OS 47.6 months
for Kd versus 40.0 months for Vd, HR=0.79; p=0.01).
"Overall survival is generally considered to be the gold
standard of endpoints because it clearly demonstrates a drug's
value in extending a patient's life, 1,2" said
David M. Reese, M.D., senior vice
president of Translational Sciences and Oncology at Amgen. "Blood
cancer therapies approved by the FDA between 2003 and 2013 only
improved overall survival by an average of 2.61 months.3
KYPROLIS and dexamethasone improved overall survival by 7.6 months,
underscoring that this regimen is a significant advancement and
should be considered a standard of care for patients with relapsed
or refractory multiple myeloma."
The National Comprehensive Cancer Network Clinical Practice
Guidelines in Oncology (NCCN Guidelines®) list Kd as the
only preferred doublet regimen at relapse for multiple myeloma.
Full OS results from the ENDEAVOR trial were published earlier this
year in The Lancet Oncology.
Adverse events observed in this updated analysis were consistent
with those previously reported for ENDEAVOR. The most common
adverse events (greater than or equal to 20 percent) in the
KYPROLIS arm were anemia, diarrhea, pyrexia, dyspnea, fatigue,
hypertension, cough, insomnia, upper respiratory tract infection,
peripheral edema, nausea, bronchitis, asthenia, back pain,
thrombocytopenia and headache.
Since its approval in 2012, more than 50,000 patients worldwide
have received KYPROLIS. The KYPROLIS clinical program continues to
focus on providing treatment options for physicians and patients
for this frequently relapsing and difficult-to-treat cancer.
KYPROLIS is available for patients whose myeloma has relapsed or
become resistant to another treatment and continues to be studied
in a range of combinations and patient populations.
About ENDEAVOR
The randomized ENDEAVOR
(RandomizEd, OpeN Label, Phase 3 Study of
Carfilzomib Plus DExamethAsone Vs
Bortezomib Plus DexamethasOne in Patients
With Relapsed Multiple Myeloma) trial of 929 patients
evaluated KYPROLIS in combination with low-dose dexamethasone,
versus Velcade with low-dose dexamethasone in relapsed or
refractory patients who previously received at least one, but not
more than three, prior therapeutic regimens. The primary endpoint
of the trial was progression-free survival, defined as the time
from treatment initiation to disease progression or death. The
primary analysis was published in The Lancet
Oncology and is described in the Prescribing
Information.
Patients received treatment until progression with KYPROLIS as a
30-minute infusion on days 1, 2, 8, 9, 15 and 16 of 28 day
treatment cycles, along with low-dose dexamethasone (20 mg). For
cycle one only, KYPROLIS was administered at 20
mg/m2 on days 1 and 2, and if tolerated was
escalated to 56 mg/m2 from day 8 of cycle one
onwards. Patients who received Velcade (1.3 mg/m2) with
low-dose dexamethasone (20 mg) were treated with Velcade
administered subcutaneously or intravenously at the discretion of
the investigator and in accordance with regional regulatory
approval of Velcade. More than 75 percent of the patients in the
control arm received Velcade subcutaneously. This study was
conducted at 235 sites worldwide. For information about this trial,
please visit www.clinicaltrials.gov under trial
identification number NCT01568866.
About Multiple Myeloma
Multiple myeloma is an
incurable blood cancer, characterized by a recurring pattern of
remission and relapse.4 It is a rare and
life-threatening disease that accounts for approximately one
percent of all cancers.5,6 In the U.S., there are more
than 118,000 people living with, or in remission from, multiple
myeloma.7 Approximately 30,280 Americans are diagnosed
with multiple myeloma each year and 12,590 patient deaths are
reported on an annual basis.7
About
KYPROLIS® (carfilzomib)
Proteasomes
play an important role in cell function and growth by breaking down
proteins that are damaged or no longer
needed.8 KYPROLIS has been shown to block
proteasomes, leading to an excessive build-up of proteins within
cells.8 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.8,9
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, 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. It is recommended to control hypertension prior to
starting KYPROLIS. 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 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,
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we or others could identify safety, side effects or manufacturing
problems with our products, including our devices, after they are
on the market.
Our results may be affected by our ability to successfully
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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)
Velcade® (bortezomib) is a registered trademark
of Millennium Pharmaceuticals, Inc.
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