THOUSAND OAKS, Calif.,
June 11, 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 the positive overall survival (OS) data
from the Phase 3 ASPIRE trial to the U.S. Prescribing Information
for KYPROLIS® (carfilzomib). Data added to the label
showed that KYPROLIS, lenalidomide and dexamethasone (KRd)
significantly reduced the risk of death by 21 percent and extended
overall survival by 7.9 months versus lenalidomide and
dexamethasone alone (Rd) in patients with relapsed or refractory
multiple myeloma (median OS 48.3 months for KRd versus 40.4 months
for Rd, HR=0.79, 95 percent CI, 0.67 – 0.95; two-sided
p=0.0091).
"Amgen is focused on advancing treatment options that have the
potential to transform outcomes for patients," said David M. Reese, M.D., senior vice president of
Translational Sciences and Oncology at Amgen. "The ASPIRE trial
showed significant improvement in survival in patients with
relapsed or refractory multiple myeloma who received KYPROLIS as
part of a triplet regimen. With this approval, the U.S. Prescribing
Information for KYPROLIS now includes positive overall survival
data from two Phase 3 trials, underscoring the important role of
proteasome inhibition in the treatment of multiple
myeloma."
Full OS results from ASPIRE were published earlier this year in
the Journal of Clinical Oncology. The safety data were
consistent with the known safety profile of KYPROLIS. The most
common adverse events (greater than or equal to 20 percent) in the
KYPROLIS arm were diarrhea, anemia, neutropenia, fatigue, upper
respiratory tract infection, pyrexia, cough, hypokalemia,
thrombocytopenia, muscle spasms, pneumonia, nasopharyngitis,
nausea, constipation, insomnia and bronchitis.
Since its approval in 2012, approximately 80,000 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
blood cancer.
About ASPIRE
The international, randomized Phase 3 ASPIRE
(CArfilzomib, Lenalidomide, and DexamethaSone versus
Lenalidomide and Dexamethasone for the treatment
of PatIents with Relapsed Multiple
MyEloma) trial evaluated KYPROLIS in combination with
lenalidomide and dexamethasone, versus lenalidomide and
dexamethasone alone, in patients with relapsed or refractory
multiple myeloma following treatment with one to three prior
regimens. The primary endpoint of the trial was progression-free
survival, defined as the time from treatment initiation to disease
progression or death. Secondary endpoints included OS, overall
response rate, duration of response, disease control rate,
health-related quality of life and safety. Patients were randomized
to receive KYPROLIS (20 mg/m2 on days 1 and 2 of
cycle one, escalating to 27 mg/m2 on days 8, 9, 15
and 16 of cycle one and continuing on days 1, 2, 8, 9, 15 and 16 of
subsequent cycles), in addition to a standard dosing schedule of
lenalidomide (25 mg per day for 21 days on, seven days off) and
low-dose dexamethasone (40 mg per week in four-week cycles), versus
lenalidomide and low-dose dexamethasone alone. The study randomized
792 patients at sites in North
America, Europe and Israel.
About Multiple Myeloma
Multiple myeloma is an incurable blood cancer, characterized by
a recurring pattern of remission and relapse.1 It is a
rare and life-threatening disease that accounts for approximately
two percent of all cancers.2,3 In the U.S., there are
more than 124,000 people living with, or in remission from,
multiple myeloma.2 Approximately 30,770 Americans
are diagnosed with multiple myeloma each year and 12,770 patient
deaths are reported on an annual basis.2
About KYPROLIS® (carfilzomib)
Proteasomes play an important role in cell function and growth
by breaking down proteins that are damaged or no longer
needed.4 KYPROLIS has been shown to block
proteasomes, leading to an excessive build-up of proteins within
cells.4 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.4,5
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 United States. Additional
regulatory applications for KYPROLIS are underway and have been
submitted to health authorities worldwide.
Important U.S. KYPROLIS® (carfilzomib) 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 control and fluid management) prior to
starting treatment with KYPROLIS and remain under close
follow‐up.
Acute Renal Failure
- Cases of acute renal failure, including some fatal renal
failure events, 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.
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. 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 side effects occurring in at least 20% of
patients receiving KYPROLIS when used alone (monotherapy) in trials
are: low red blood cell count, tiredness (fatigue), low platelets,
nausea, fever, difficulty breathing, diarrhea, headache, cough,
swelling of the lower legs or hands.
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
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by Amgen, including our most recent annual report on Form 10-K and
any subsequent periodic reports on Form 10-Q and current reports
on Form 8-K. Unless otherwise noted, Amgen is providing this
information as of the date of this news release and does not
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CONTACT: Amgen, Thousand Oaks
Kristen Davis, 805-447-3008
(Media)
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References
- Jakubowiak A. Management Strategies for Relapsed/Refractory
Multiple Myeloma: Current Clinical Perspectives. Seminars
in Hematology. 2012; 49(3)(1),S16-S32.. 2012;
49(3)(1),S16-S32.
- National Cancer Institute. SEER Stat Fact Sheets: Myeloma.
Available
at: http://seer.cancer.gov/statfacts/html/mulmy.html. Accessed
on May 30, 2018.
- American Cancer Society. About Multiple Myeloma. Available
at https://www.cancer.org/content/dam/CRC/PDF/Public/8738.00.pdf.
Accessed on April 19, 2018.
- 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.. 2012; 121(6):893-897.
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