THOUSAND OAKS, Calif.,
Jan. 21, 2016 /PRNewswire/
-- Amgen (NASDAQ: AMGN) today announced that the U.S. Food and
Drug Administration (FDA) has approved the supplemental New Drug
Application (sNDA) of Kyprolis® (carfilzomib) for
Injection 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. The FDA also approved Kyprolis as a single agent for the
treatment of patients with relapsed or refractory multiple myeloma
who have received one or more lines of therapy. This FDA decision
converts to full approval the initial accelerated approval Kyprolis
received in July 2012 as a single
agent.
Experience the interactive Multimedia News Release here:
http://www.multivu.com/players/English/74140510-kyprolis-endeavor-expanded-approval/.
"Kyprolis is the only approved therapy for relapsed multiple
myeloma with proven efficacy as a single agent, doublet and
triplet combination that is offered in a variety of doses to meet
individual patient needs," said Sean E.
Harper, M.D., executive vice president of Research and
Development at Amgen. "Importantly, this new approval supports
the use of Kyprolis as a backbone therapy for the management of
relapsed multiple myeloma, a difficult-to-treat blood cancer."
"Multiple myeloma remains an incurable disease where relapse
inevitably occurs and over time patients become resistant to
treatments," said Dr. Ruben
Niesvizky, director of the Multiple Myeloma Center at Weill
Cornell Medicine and New York-Presbyterian/Weill Cornell Medical
Center. "As a clinician, I'm pleased with the tremendous progress
that we have seen in the past 12 months in multiple myeloma
treatment. This FDA approval is important because it provides
physicians with flexible options for Kyprolis use in helping to
manage this challenging disease."
The approval is based on results from the Phase 3 head-to-head
ENDEAVOR study. This was a superiority trial in which the primary
endpoint was progression-free survival (PFS). The data showed
patients with relapsed multiple myeloma treated with Kyprolis and
dexamethasone achieved 50 percent greater PFS of 18.7 months
compared to 9.4 months in those receiving Velcade®
(bortezomib) and dexamethasone (HR=0.53; 95 percent CI: 044, 0.65
p<0.0001), a current standard of care in relapsed
multiple myeloma. Patients in the study were treated until disease
progression. The most common adverse reactions (greater than or
equal to 20 percent) in the Kyprolis arm were anemia, diarrhea,
dyspnea, fatigue, insomnia, pyrexia and thrombocytopenia.
This new indication for Kyprolis is the second in six months. In
July 2015, the FDA approved another expanded indication for
Kyprolis in combination with lenalidomide and dexamethasone (KRd)
for the treatment of patients with multiple myeloma who have
received one to three prior lines of therapy.
Multiple myeloma is an incurable blood cancer, characterized by
a recurring pattern of remission and relapse.1 It is a
rare and very aggressive disease that accounts for approximately
one percent of all cancers.2-4 In the U.S., there are
nearly 90,000 people living with, or in remission from, multiple
myeloma.5 Approximately, 26,850 Americans are diagnosed
with multiple myeloma each year and 11,240 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 (Kd), 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
As stated above, Kd was superior to bortezomib and dexamethasone
(Vd) and demonstrated significantly longer PFS. Improvement in PFS
in the Kd arm compared to the Vd arm was seen across all
pre-specified subgroups, including bortezomib-naïve patients, those
with high- or standard-risk cytogenetics and with or without prior
transplantation.
Kd also demonstrated improvement over Vd for secondary
endpoints, achieving a higher overall response rate (77 percent vs.
63 percent; p<0.0001) and lower rate of grade 2 or higher
neuropathy events (6 percent [95 percent CI: 4, 8] vs. 32 percent
[95 percent CI: 28, 36]). In the Kyprolis and bortezomib groups,
54.3 percent and 28.6 percent of patients achieved a very good
partial response or better (p<0.0001), and 12.5 percent
and 6.2 percent of patients achieved a complete response or better
(p<0.0001), respectively. Overall survival data are not
yet mature and continue to be monitored.
Treatment discontinuation due to adverse events and on-study
deaths were comparable between the two arms. A number of known
adverse drug reactions were reported at a higher rate in the
Kyprolis group compared with the bortezomib group, including
any-grade dyspnea, hypertension, pyrexia, and cough as were
any-grade cardiac failure (grouped term; 8 percent vs. 3 percent)
and acute renal failure (grouped term; 8 percent vs. 5
percent).
Rates of grade 3 or higher adverse events were 73 percent in the
Kyprolis group and 67 percent in the bortezomib group. Grade 3 or
higher adverse events of interest in the Kyprolis and bortezomib
groups included hypertension (preferred term; 9 percent vs. 3
percent), dyspnea (preferred term; 5 percent vs. 2 percent),
cardiac failure (grouped term; 5 percent vs. 2 percent), acute
renal failure (grouped term; 4 percent vs. 3 percent), ischemic
heart disease (grouped term; 2 percent vs. 2 percent) and pulmonary
hypertension (grouped term; 0.6 percent vs. 0.2 percent).
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 1 only, Kyprolis was administered at 20
mg/m2 on days 1 and 2, and if tolerated followed by
escalation to 56 mg/m2 from day 8. Patients who
tolerated 56 mg/m2 in Cycle 1 were kept at this
dose for subsequent cycles. Patients who received bortezomib (1.3
mg/m2) with low-dose dexamethasone (20 mg) were
administered bortezomib subcutaneously or intravenously at the
discretion of the investigator and in accordance with regulatory
approval of bortezomib. More than 75 percent of the patients in the
control arm received bortezomib 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 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.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 The irreversibility of Kyprolis' binding has
also been shown to offer a more sustained inhibition of the
targeted enzymes.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, Israel, Kuwait, Mexico, Thailand, Colombia, Korea, Canada and the European Union. Additional
regulatory applications for Kyprolis are underway and have been
submitted to health authorities worldwide.
Kyprolis is a product of Onyx Pharmaceuticals, Inc. Onyx
Pharmaceuticals is a subsidiary of Amgen and holds development and
commercialization rights to Kyprolis globally, excluding
Japan.
For more information, please visit www.kyprolis.com.
Patient Support Program
Amgen is proud to offer Onyx
Pharmaceuticals 360® (Onyx 360) which is a patient
support program designed to provide personalized services to
patients living with cancer. Upon enrollment, patients are paired
with a dedicated Onyx 360 Oncology Nurse Ambassador who is trained
to help navigate their treatment journey and address daily and long
term concerns. Onyx 360 also provides access to a network of
resources and third-party services including transportation,
emotional support and financial and product reimbursement
assistance. Onyx 360 services are provided to patients at no cost.
For more information, please visit
www.kyprolis.com/support-during-treatment.
Editor's Note: Dr. Niesvizky is
an advisory board member for and paid consultant to Onyx
Pharmaceuticals, Inc.
Important Safety Information Regarding Kyprolis®
(carfilzomib) for Injection
INDICATION(S)
- KYPROLIS® (carfilzomib) is indicated 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.
- KYPROLIS® (carfilzomib) is indicated as a single
agent for the treatment of patients with relapsed or refractory
multiple myeloma who have received one or more lines of
therapy.
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.
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 neuroradiological 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 events 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 events 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
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 biologics manufacturing 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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References
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Accessed on January 13, 2016.
- American Cancer Society. Multiple Myeloma. Available at:
http://www.cancer.org/acs/groups/cid/documents/webcontent/003121-pdf.pdf.
Accessed on January 13, 2016.
- Palumbo A and Anderson K. Multiple myeloma. N Engl J
Med. 2011;364:1046–60.
- National Cancer Institute. SEER Stat Fact Sheets: Myeloma.
Available at: http://seer.cancer.gov/statfacts/html/mulmy.html.
Accessed on January 13, 2016.
- National Cancer Institute. NCI Dictionary of Cancer Terms.
Available at:
http://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=44782.
Accessed on January 13, 2016.
- Moreau P, Richardson PG, Cavo M, et al. Proteasome Inhibitors
in Multiple Myeloma: 10 Years Later. Blood. 2012;
120(5):947-959.
- Kyprolis® [package insert]. Thousand Oaks, CA: Amgen; 2016.
- Kortuem KM and Stewart AK. Carfilzomib. Blood. 2012;
121(6):893-897.
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