THOUSAND OAKS, Calif.,
Sept. 27, 2016 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today
announced top-line results of the Phase 3 CLARION trial, which
evaluated an investigational regimen of KYPROLIS®
(carfilzomib), melphalan and prednisone (KMP) versus
Velcade® (bortezomib), melphalan and prednisone (VMP)
for 54 weeks in patients with newly diagnosed multiple myeloma who
were ineligible for hematopoietic stem-cell transplant. The trial
did not meet the primary endpoint of superiority in
progression-free survival (PFS) (median PFS 22.3 months for KMP
versus 22.1 months for VMP, HR = 0.91, 95 percent CI, 0.75 - 1.10).
While the data for overall survival, a secondary endpoint, are not
yet mature, the observed hazard ratio (KMP versus VMP) was 1.21 (95
percent CI, 0.90 - 1.64). Neither result was statistically
significant.
Overall, the adverse events in the KMP arm were consistent with
the known safety profile of KYPROLIS. The incidence of Grade 3 or
higher adverse events was 74.7 percent in the KMP arm and 76.2
percent in the VMP arm. Fatal treatment-emergent adverse events
occurred in 6.5 percent of KMP patients and 4.3 percent of VMP
patients. The incidence of Grade 2 or higher peripheral neuropathy,
a secondary endpoint, was 2.5 percent in the KMP arm and 35.1
percent in the VMP arm.
These data will be submitted to a future medical conference and
for publication.
"Based on studies in the KYPROLIS label, including the ENDEAVOR
study, a head-to-head comparison of KYPROLIS to Velcade in patients
with relapsed or refractory multiple myeloma, we know KYPROLIS to
be a major advance in proteasome inhibitor therapy," said
Sean E. Harper, M.D., executive vice
president of Research and Development at Amgen. "The CLARION
results, generated in the context of a melphalan-containing
regimen, are disappointing, especially given the robust data we've
seen in the second-line setting. However, the myeloma landscape has
changed dramatically since the design of the CLARION study with
very few newly diagnosed patients treated with melphalan-based
regimens, particularly in the U.S. We remain committed to
exploring KYPROLIS in combination with other agents to advance the
treatment of multiple myeloma."
Amgen supports a number of investigator-sponsored studies, and a
Phase 3 study evaluating KYPROLIS in combination with lenalidomide
plus dexamethasone (KRd) versus Velcade in combination with
lenalidomide plus dexamethasone (VRd) in newly diagnosed multiple
myeloma patients. This trial, called E1A11 or ENDURANCE, is
underway independently by the ECOG-ACRIN Cancer Research Group with
funding provided by the National Cancer Institute (NCI) and its
National Clinical Trials Network. Over 750 institutions nationwide
are currently enrolling patients in the study (NCT01863550).
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 the CLARION Study
The CLARION study was a Phase
3 head-to-head multicenter, open-label, randomized study in
transplant-ineligible patients with newly diagnosed multiple
myeloma. A total of 955 patients were randomized 1:1 to receive
KYPROLIS, melphalan and prednisone or Velcade, melphalan and
prednisone for 54 weeks. The median patient age was 72.
The KMP regimen consisted of KYPROLIS as a 30 minute intravenous
(IV) infusion on days 1, 2, 8, 9, 22, 23, 29 and 30 during each
42-day cycle (20 mg/m2 on days 1 and 2 of cycle 1; 36
mg/m2 thereafter), melphalan 9 mg/m2 on days
1–4, and prednisone 60 mg/m2 on days 1–4.
Amgen Webcast Investor Call
Amgen will host a webcast call for the investment community
on Tuesday, Sept. 27, 2016, at 8:30 a.m.
ET. Sean E. Harper, M.D., executive vice president of
Research and Development at Amgen, along with KYPROLIS
clinical investigators, will participate in the call to
discuss the CLARION data.
Live audio of the investor call will be simultaneously broadcast
over the Internet and will be available to members of the news
media, investors and the general public.
The webcast, as with other selected presentations regarding
developments in Amgen's business given by management at
certain investor and medical conferences, can be found
on Amgen's website, www.amgen.com, under Investors.
Information regarding presentation times, webcast availability and
webcast links are noted on Amgen's Investor Relations
Events Calendar. The webcast will be archived and available for
replay for at least 90 days after the event.
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 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, Brazil and the European Union. Additional
regulatory applications for KYPROLIS are underway and have been
submitted to health authorities worldwide.
For more U.S. information, please visit www.kyprolis.com.
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
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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Velcade® (bortezomib) is a registered trademark of
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CONTACT: Amgen, Thousand
Oaks
Kristen Davis, 805-447-3008
(media)
Kristen Neese, 805-313-8267
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(investors)
References
- Jakubowiak A. Management Strategies for Relapsed/Refractory
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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 March 9, 2015.
- American Cancer Society. Multiple myeloma.
http://www.cancer.org/acs/groups/cid/documents/webcontent/003121-pdf.pdf.
Accessed on: October 30, 2015.
- National Cancer Institute. SEER Stat Fact Sheets: Myeloma.
Available at: http://seer.cancer.gov/statfacts/html/mulmy.html.
Accessed on August 5, 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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