THOUSAND OAKS, Calif.,
May 27, 2016 /PRNewswire/
-- Amgen (NASDAQ:AMGN) today announced that the Committee
for Medicinal Products for Human Use (CHMP) of the European
Medicines Agency has adopted a positive opinion to extend the
current indication for Kyprolis® (carfilzomib) to
include treatment in combination with dexamethasone alone for adult
patients with multiple myeloma who have received at least one prior
therapy.
"In the first ever comparative Phase 3 head-to-head study of two
proteasome inhibitors in relapsed multiple myeloma, Kyprolis in
combination with dexamethasone nearly doubled progression-free
survival compared to a current standard of care regimen," said
Sean E. Harper, M.D., executive vice
president of Research and Development at Amgen. "We are pleased
that the CHMP has recognized these robust data with a positive
opinion, and we look forward to ensuring approval of this extended
indication of Kyprolis."
The CHMP positive opinion is based on data from the Phase 3
head-to-head ENDEAVOR study in which patients with multiple myeloma
treated with Kyprolis plus dexamethasone achieved superior
progression-free survival (PFS) of 18.7 months compared to 9.4
months in those receiving Velcade® (bortezomib) plus
dexamethasone, (HR=0.53; 95 percent CI: 0.44,0.65
p<0.0001). The most common adverse reactions that
occurred in greater than 20 percent of patients in the Kyprolis arm
were anemia, fatigue, diarrhea, thrombocytopenia, nausea, pyrexia,
dyspnea, respiratory tract infection, cough and peripheral
edema.
The CHMP positive opinion will now be reviewed by the European
Commission (EC) and if granted, the marketing authorization will be
extended to include Kyprolis in combination with dexamethasone in
the 28 member countries of the European Union, as well as
Iceland, Lichtenstein
and Norway. The extended indication adopted by the CHMP is:
Kyprolis in combination with either lenalidomide and dexamethasone
or dexamethasone alone is indicated for the treatment of adult
patients with multiple myeloma who have received at least one prior
therapy.
The EC previously granted marketing authorization for Kyprolis
in combination with lenalidomide and dexamethasone for the
treatment of adult patients with multiple myeloma who have received
at least one prior therapy based on results of the ASPIRE study in
November 2015. Today's CHMP positive
opinion follows the U.S. Food and Drug Administration's approval of
a supplemental New Drug Application based on the ENDEAVOR results
in January 2016.
About Multiple Myeloma
Multiple myeloma is characterized by a recurring pattern of
remission and relapse.1 It is a rare and very aggressive
orphan disease that accounts for approximately one percent of all
cancers worldwide.2-4 In Europe, approximately 39,000 patients are
diagnosed with multiple myeloma each year and 24,000 patient deaths
are reported on an annual basis.5
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 bortezomib with
low-dose dexamethasone in patients whose multiple myeloma has
relapsed after at least one, but not more than three prior
therapeutic regimens. The primary endpoint of the trial was PFS,
defined as the time from treatment initiation to disease
progression or death. In a clinical trial, measuring the PFS is one
way to demonstrate how well a treatment works.6
This study was conducted at 235 sites worldwide. For information
about this trial, please visit www.clinicaltrials.gov under trial
identification number NCT01568866.
About Kyprolis® (carfilzomib)
Proteasomes play an important role in cell function and growth
by breaking down proteins that are damaged or no longer
needed.7 Kyprolis has been shown to block
proteasomes, leading to an excessive build-up of proteins within
cells.7 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.7,8
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, Israel, Kuwait, Mexico, Thailand, Colombia, Korea, Canada, Switzerland, Russia and the European Union. Additional
regulatory applications for Kyprolis are underway and have been
submitted to health authorities worldwide.
For more 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.
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.
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.
Full prescribing information for the U.S. is available
at www.kyprolis.com.
About Amgen
Amgen is committed to unlocking the potential of biology
for patients suffering from serious illnesses by discovering,
developing, manufacturing and delivering innovative human
therapeutics. This approach begins by using tools like advanced
human genetics to unravel the complexities of disease and
understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and
leverages its expertise to strive for solutions that improve health
outcomes and dramatically improve people's lives. A biotechnology
pioneer since 1980, Amgen has grown to be one of the world's
leading independent biotechnology companies, has reached millions
of patients around the world and is developing a pipeline of
medicines with breakaway potential.
For more information, visit www.amgen.com and follow
us on www.twitter.com/amgen.
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CONTACT:
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References
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accessed on May 9, 2016.
- American Cancer Society. Multiple
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the approval of cancer drugs and
biologics.http://www.fda.gov/downloads/Drugs/Guidances/ucm071590.pdf.
Accessed on May 10, 2016.
- 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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