THOUSAND OAKS, Calif.,
Nov. 10, 2016 /PRNewswire/ -- Amgen
(NASDAQ:AMGN) today announced a collaboration with Janssen Biotech,
Inc. to evaluate the combination of Amgen's KYPROLIS®
(carfilzomib) and Janssen's DARZALEX® (daratumumab) in
multiple clinical studies in patients with multiple myeloma. Under
the terms of the agreement, the companies may elect to supply drug
only or supply drug and share development costs on a study-by-study
basis.
The first study initiated as part of this agreement is a Phase 3
registrational trial evaluating KYPROLIS in combination with
DARZALEX and dexamethasone compared to KYPROLIS and dexamethasone
alone in patients with multiple myeloma who have had one, two or
three prior lines of therapy. The rationale for combining these
agents is that they have demonstrated substantial activity in
multiple myeloma, with distinct and complementary mechanisms of
action. The study is anticipated to start enrolling patients in
April 2017.
"Given the relapsing nature of multiple myeloma, several options
are needed to attack the disease differently and keep patients in
remission as long as possible," said Sean
E. Harper, M.D., executive vice president of Research and
Development at Amgen. "We are excited to collaborate with Janssen
to evaluate the potential of combining KYPROLIS, a powerful
proteasome inhibitor, with DARZALEX, the first human anti-CD38
monoclonal antibody for the treatment of multiple myeloma in the
relapsed setting."
As part of an earlier and separate agreement, Amgen is also
supplying KYPROLIS for Janssen's open-label Phase 1b study. The
combination of DARZALEX and KYPROLIS is being investigated in this
Phase 1b study in two cohorts. One cohort includes DARZALEX in
combination with KYPROLIS and dexamethasone in patients who
previously received one to three prior lines of therapy. The second
cohort includes DARZALEX in combination with KYPROLIS,
REVLIMID® (lenalidomide) and dexamethasone in subjects
with newly diagnosed multiple myeloma, regardless of
transplantation eligibility. Both Phase 1 cohorts are fully
enrolled.
About the Phase 3 Study Design
The proposed study
design is a Phase 3, open-label, randomized study in multiple
myeloma patients with one, two or three prior lines of therapy.
Patients will be treated to progression. In the first arm, patients
will receive KYPROLIS twice weekly at 56 mg/m2 and
dexamethasone in combination with DARZALEX (KdD). In the second arm
(control), patients will receive KYPROLIS twice weekly at 56
mg/m2 and dexamethasone (Kd). The primary endpoint is
progression-free survival (PFS) and the key secondary endpoints are
overall response rate, minimal residual disease and overall
survival.
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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The scientific information discussed in this news release
relating to new indications for our products is preliminary and
investigative and is not part of the labeling approved by
the U.S. Food and Drug Administration or
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DARZALEX® (daratumumab) is a registered trademark of
Janssen Biotech, Inc.
REVLIMID® (lenalidomide) is a registered trademark of
Celgene Corporation.
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 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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