THOUSAND OAKS, Calif.,
June 6, 2016 /PRNewswire/
-- Amgen (NASDAQ:AMGN) today announced data from a secondary
analysis of the pivotal Phase 3 ASPIRE trial that showed
Kyprolis® (carfilzomib) for Injection in combination
with lenalidomide and dexamethasone (KRd) improved progression-free
survival (PFS) and overall response rate (ORR) compared to
lenalidomide and dexamethasone (Rd) alone in patients with relapsed
multiple myeloma with early disease progression after initial
therapy or transplant. The results were presented today at the
52nd Annual Meeting of the American Society of Clinical
Oncology (ASCO).
The analysis showed that patients relapsing within one year of
initial therapy treated with KRd (n=87) experienced a median PFS of
24.1 months versus 12.5 months in those treated with Rd (n=72)
(HR=0.75; 95 percent CI: 0.50-1.13). In addition, ORR in the KRd
arm was 79.3 percent versus 61.1 percent in the Rd arm. Patients
relapsing early after first prior transplant treated with KRd
(n=48) experienced a median PFS of 17.3 months versus 11.1 months
in those treated with Rd (n=49) (HR=0.87; 95 percent CI:
0.54-1.41). In addition, the ORR in the KRd arm was 83.3 percent
versus 61.2 percent in the Rd arm. Grade 3 adverse events that
occurred at least five percent more frequently in the KRd arm
compared to the Rd arm in either subgroup were hypokalemia,
neutropenia, febrile neutropenia, hypophosphatemia and respiratory
tract infection (ASCO abstract #8045).
"A goal in treating relapsed multiple myeloma is to get patients
into remission, and keep them in remission as long as possible. For
some patients who relapse early, this may be a sign of a more
aggressive disease1," said Sean
E. Harper, M.D., executive vice president of Research and
Development at Amgen. "This analysis showed that in early relapsing
multiple myeloma patients, the addition of Kyprolis to lenalidomide
and dexamethasone resulted in patients living longer without their
disease progressing, a significant milestone for patients living
with this difficult-to-treat disease."
ASCO Abstract #8045: Carfilzomib, Lenalidomide, and
Dexamethasone (KRd) vs. Lenalidomide and Dexamethasone (Rd) in
Patients with Relapsed Multiple Myeloma (RMM) and Early Progression
During Prior Therapy: Secondary Analysis From the Phase 3 Study
ASPIRE (NCT01080391)
An exploratory sub-group analysis assessed the efficacy and
safety of KRd compared with Rd alone in 159 patients with multiple
myeloma who had relapsed less than or equal to one year from their
first treatment. A second sub-group analysis examined 97 patients
with multiple myeloma who had relapsed less than or equal to one
year from prior transplant.
- In patients who had relapsed less than or equal to one year
from their first treatment, median PFS in the KRd arm was 24.1
months versus 12.5 months for Rd (HR=0.75; 95 percent CI:
0.50-1.13), and ORR was 79.3 percent for KRd versus 61.1 percent
for Rd. In addition, 21.8 percent of patients in the KRd arm
experienced a complete response versus 4.2 percent treated with
Rd.
- In patients who had relapsed less than or equal to one year
after transplant, median PFS in the KRd arm was 17.3 months versus
11.1 months for Rd (HR=0.87; 95 percent CI: 0.54-1.41), and ORR was
83.3 percent for KRd versus 61.2 percent for Rd. Complete responses
in the KRd and Rd arms were 12.5 percent and 4.1 percent,
respectively.
- Grade 3 or higher adverse events that occurred in greater than
or equal to five percent more frequently in KRd than Rd in both
groups were hypokalemia, neutropenia, febrile neutropenia,
hypophosphatemia and respiratory tract infection.
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 multiple myeloma
following treatment with one to three prior regimens. The primary
endpoint of the trial was PFS, defined as the time from treatment
initiation to disease progression or death. Secondary endpoints
included overall survival (OS), overall response rate (ORR),
duration of response (DOR), disease control rate, health-related
quality of life (HR-QoL) and safety. Patients were randomized to
receive Kyprolis (20 mg/m2 on days 1 and 2 of cycle one only,
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, 7 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.2 It is a rare and very
aggressive disease that accounts for approximately one percent of
all cancers.2,3 In the U.S., there are nearly
90,000 people living with, or in remission from, multiple
myeloma.4 Approximately, 30,330 Americans are diagnosed
with multiple myeloma each year and 12,650 patient deaths are
reported on an annual basis.5
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 Kyprolis® (carfilzomib)
Proteasomes
play an important role in cell function and growth by breaking down
proteins that are damaged or no longer needed.5 Kyprolis
has been shown to block proteasomes, leading to an excessive
build-up of proteins within cells.5 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.5,6
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.
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.
Important Safety Information Regarding
Kyprolis® (carfilzomib) for Injection
INDICATIONS
- 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 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
1 Ludwig H, et al. Carfilzomib, Lenalidomide, and
Dexamethasone (KRd) vs. Lenalidomide and Dexamethasone (Rd) in
Patients with Relapsed Multiple Myeloma (RMM) and Early Progression
During Prior Therapy: Secondary Analysis From the Phase 3 Study
ASPIRE (NCT01080391). ASCO Abstract #8045. 2016.
2 GLOBCAN 2012. Global Prevalence and Incidence.
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Accessed on May 11, 2016.
3 American Cancer Society. Multiple Myeloma. Available
at:
http://www.cancer.org/acs/groups/cid/documents/webcontent/003121-pdf.pdf.
Accessed on May 11, 2016.
4 National Cancer Institute. SEER Stat Fact Sheets:
Myeloma. Available at:
http://seer.cancer.gov/statfacts/html/mulmy.html. Accessed on
May 11, 2016.
5 Moreau P, Richardson PG, Cavo M, et al. Proteasome
Inhibitors in Multiple Myeloma: 10 Years Later. Blood. 2012;
120(5):947-959.
6 Kortuem KM and Stewart AK. Carfilzomib. Blood.
2012; 121(6):893-897.
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