THOUSAND OAKS, Calif.,
Feb. 28, 2017 /PRNewswire/
-- Amgen (NASDAQ:AMGN) today announced positive results from a
planned overall survival (OS) interim analysis of the Phase 3
head-to-head ENDEAVOR trial. The study met the key secondary
endpoint of OS, demonstrating that patients with relapsed or
refractory multiple myeloma treated with KYPROLIS®
(carfilzomib) and dexamethasone (Kd) lived 7.6 months longer than
those treated with Velcade® (bortezomib) and
dexamethasone (Vd) (median OS 47.6 months for Kd versus 40.0 for
Vd, HR = 0.79, 95 percent CI, 0.65 – 0.96). This Kd regimen
administered with 56 mg/m2 KYPROLIS twice weekly is
already approved in the U.S., European Union and other countries
based on the primary analysis of progression-free survival (PFS) in
the ENDEAVOR study.
"For an incurable disease like multiple myeloma, a major
treatment goal for oncologists and hematologists is to help
patients live as long as possible," said study co-author and
investigator Meletios A. Dimopoulos, M.D., professor of
Clinical Therapeutics at the National and Kapodistrian University
of Athens, School of Medicine.
"Based on these data, we now know that KYPROLIS not only
significantly extended progression-free survival compared to
Velcade, but also overall survival, making it a clinically
meaningful advance in the treatment of relapsed or refractory
multiple myeloma."
"These results confirm the superiority of KYPROLIS over Velcade
in relapsed or refractory multiple myeloma patients," said
Sean E. Harper, M.D., executive vice
president of Research and Development at Amgen. "A survival benefit
has rarely been demonstrated in relapsed or refractory multiple
myeloma. ENDEAVOR is the only study to demonstrate a survival
benefit in a head-to-head comparison with a current standard of
care regimen. These results further support KYPROLIS as a
foundational therapy in this patient population."
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.
Detailed results will be presented on Saturday, March 4 at
7:30 a.m. IST at the 16th
International Myeloma Workshop in New
Delhi. Amgen plans to submit these results to regulatory
agencies worldwide to support a potential label update to the
ENDEAVOR study results.
The KYPROLIS clinical program continues to focus on providing
solutions for physicians and patients in treating 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 (Kd), versus bortezomib with low-dose
dexamethasone (Vd) 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. 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 1 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 Cycle 1 onwards. Patients who received bortezomib (1.3
mg/m2) with low-dose dexamethasone (20 mg) were treated
with bortezomib administered subcutaneously or intravenously at the
discretion of the investigator and in accordance with regional
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 or the News Release section of
Amgen.com.
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 very aggressive
disease that accounts for approximately one percent of all
cancers.2,3 In the U.S., there are nearly 95,000 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.4
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, 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
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. 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.
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
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contains forward-looking statements that are based on the current
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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
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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
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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
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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)
References
- Jakubowiak A. Management Strategies for Relapsed/Refractory
Multiple Myeloma: Current Clinical Perspectives. Seminars in
Hematology. 2012; 49(3)(1),S16-S32.
- GLOBOCAN 2012. Global Prevalence and Incidence. Available at:
http://globocan.iarc.fr/old/summary_table_pop_prev.asp?selection=224900&title=World&sex=0&window=1&sort=0&submit=%C2%A0Execute%C2%A0.
Accessed on January 6, 2017.
- American Cancer Society. Multiple myeloma. Available at:
http://www.cancer.org/acs/groups/cid/documents/webcontent/003121-pdf.pdf.
Accessed on January 6, 2017.
- National Cancer Institute. SEER Stat Fact Sheets: Myeloma.
Available at: http://seer.cancer.gov/statfacts/html/mulmy.html.
Accessed on January 6, 2017.
- 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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