THOUSAND OAKS, Calif.,
July 23, 2015 /PRNewswire/
-- Amgen (NASDAQ:AMGN) today announced the submission of a
supplemental New Drug Application (sNDA) to the U.S. Food and Drug
Administration (FDA) for Kyprolis® (carfilzomib) for
Injection to seek an expanded indication for the treatment of
patients with a form of blood cancer, relapsed multiple myeloma,
who have received at least one prior therapy. Kyprolis currently
has accelerated approval in the U.S. for the treatment of patients
with relapsed multiple myeloma as a monotherapy.
The sNDA is based on data from the global Phase 3 ENDEAVOR
trial. The ENDEAVOR study is the first of two head-to-head Phase 3
trials of Kyprolis versus Velcade® (bortezomib).
Relapsed multiple myeloma patients treated with Kyprolis and
dexamethasone in the ENDEAVOR study lived twice as long without
their disease worsening, demonstrating statistically and clinically
significant superiority over Velcade (median progression-free
survival [PFS] 18.7 months versus 9.4 months, HR=0.53, 95 percent
CI, 0.44 – 0.65; p<0.0001).
"Submission of this new sNDA for Kyprolis is important because
if approved, it will mean more treatment options for patients with
this serious disease. Multiple myeloma has historically been one of
the most difficult to treat diseases because of the inherent
complexities related to the recurring pattern of remission and
relapse," said Sean E. Harper, M.D.,
executive vice president of Research and Development at Amgen. "The
ENDEAVOR study showed that patients who had failed at least one
prior therapy were half as likely to see their disease worsen if
they received Kyprolis. This is yet another data set that
illustrates Kyprolis' potential to extend the time patients live
without their disease progressing and improve the depth and
duration of a response."
The Kyprolis combination demonstrated superiority over the
Velcade combination for secondary objectives of higher overall
response rate and lower neuropathy events. Overall survival data
are not yet mature and continue to be monitored.
Treatment discontinuation due to adverse events and on-study
deaths was comparable between the two arms. The rates of cardiac
failure and renal failure for Kyprolis were comparable to those
observed in the Phase 3 ASPIRE study. In ENDEAVOR, the rates for
cardiac and renal failure were higher in the Kyprolis arm versus
the Velcade arm. There was also an increase in the incidence of
hypertension and dyspnea in the Kyprolis arm compared to Velcade in
ENDEAVOR and than that observed in the ASPIRE study.
Based on the Phase 3 ASPIRE study Amgen continues to work with
the FDA on the related sNDA in the U.S. and with the European Union
(EU) regulatory authorities for the Marketing Authorization
Application for Kyprolis. Following potential approval based
on the ASPIRE study, Amgen plans to submit ENDEAVOR for potential
authorization in the EU.
Kyprolis Head-to-Head Studies
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 dexamethasone, versus Velcade with dexamethasone 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.
Patients received Kyprolis as a 30-minute infusion along with
dexamethasone (20 mg). Administer Kyprolis at a starting dose of 20
mg/m2 in Cycle 1 on Days 1 and 2. If tolerated,
escalate the dose to a target dose of 56 mg/m2 on Day 8
of Cycle 1. Patients were kept at 56 mg/m2 on days
9, 15 and 16 on a 28 day cycle. Patients who tolerated 56
mg/m2 in Cycle 1 were kept at this dose for subsequent
cycles on days 1, 2, 8, 9, 15 and 16 on a 28 day cycle. Patients
who received Velcade (1.3 mg/m2) with dexamethasone (20
mg) were administered Velcade subcutaneously or intravenously at
the discretion of the investigator and in accordance with
regulatory approval of Velcade. More than 75 percent of the
patients in the control arm received Velcade subcutaneously. This
study was conducted at 235 sites worldwide. For information about
this trial, please visit www.clinicaltrials.gov under trial
identification number NCT01568866.
Kyprolis is also being evaluated in the CLARION study, a
head-to-head Phase 3 multicenter, open-label, randomized study in
transplant-ineligible patients with newly diagnosed multiple
myeloma. The study is evaluating the safety and efficacy of
carfilzomib, melphalan and prednisone versus bortezomib, melphalan
and prednisone. For information about this trial, please visit
www.clinicaltrials.gov under trial identification number
NCT01818752.
About Multiple Myeloma
Multiple myeloma is the second
most common hematologic cancer.1 In the U.S., there are
nearly 96,000 people living with, or in remission from, multiple
myeloma.2 The estimated number of new cases of multiple
myeloma in 2014 was more than 24,000 and the estimated number of
deaths was 11,090.2
About Kyprolis® (carfilzomib) for
Injection
Kyprolis® (carfilzomib) for Injection
is indicated as a single agent for the treatment of patients with
multiple myeloma who have received at least two prior therapies
including bortezomib and an immunomodulatory agent and have
demonstrated disease progression on or within 60 days of completion
of the last therapy. Approval is based on response rate. Clinical
benefit, such as improvement in survival or symptoms, has not been
verified.
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. Kyprolis is also approved
for use in Argentina, Israel, Mexico and Thailand. For more information about Kyprolis,
visit www.kyprolis.com.
Important Safety Information Regarding Kyprolis®
(carfilzomib) for Injection
This safety information is
specific to the current U.S. approved indication, which is based on
Phase 2 studies.
Safety data have been evaluated in 526 patients with relapsed
and/or refractory multiple myeloma who received single-agent
Kyprolis. There were 37 deaths in the Phase 2 studies, or 7 percent
of patients. The most common causes of death, other than disease
progression, were cardiac (5 patients), end-organ failure (4
patients) and infection (4 patients). Important warnings and
precautions include cardiac arrest, congestive heart failure,
myocardial ischemia, pulmonary hypertension, pulmonary
complications, infusion reactions, tumor lysis syndrome,
thrombocytopenia, hepatic toxicity and embryo-fetal toxicity.
Death due to cardiac arrest has occurred within a day of
Kyprolis administration. Patients with New York Heart Association
Class III and IV heart failure, myocardial infarction in the
preceding 6 months and conduction abnormalities uncontrolled by
medications were not eligible for the clinical trials. These
patients may be at greater risk for cardiac complications.
Pulmonary arterial hypertension (PAH) was reported in 2 percent
of patients treated with Kyprolis and was Grade 3 or greater in
less than 1 percent of patients. Dyspnea was reported in 35 percent
of patients enrolled in clinical trials. Grade 3 dyspnea occurred
in 5 percent; no Grade 4 events and 1 death (Grade 5) was
reported.
Infusion reactions, characterized by a spectrum of systemic
symptoms including fever, chills, arthralgia, myalgia, facial
flushing, facial edema, vomiting, weakness, shortness of breath,
hypotension, syncope, chest tightness, or angina can occur
immediately following or up to 24 hours after administration of
Kyprolis. Administration of dexamethasone prior to Kyprolis reduces
the incidence and severity of reactions. Tumor lysis syndrome (TLS)
occurred following Kyprolis administration in <1 percent of
patients. Patients with multiple myeloma and a high tumor burden
should be considered to be at greater risk for TLS.
Thrombocytopenia following Kyprolis administration resulted in a
dose reduction in 1 percent of patients and discontinuation of
treatment with Kyprolis in <1 percent of patients.
Cases of hepatic failure, including fatal cases, have been
reported (<1 percent). Kyprolis can cause elevations of serum
transaminases and bilirubin.
Cases of thrombotic thrombocytopenic purpura/hemolytic uremic
syndrome (TTP/HUS) including fata outcome have been reported.
Treatment with Kyprolis should be discontinued if signs and
symptoms of TTP/HUS occur.
Cases of posterior reversible encephalopathy syndrome
(PRES) have been reported. Treatment with Kyprolis should be
discontinued if PRES is suspected.
There are no adequate and well-controlled studies in pregnant
women using Kyprolis. Females of reproductive potential should be
advised to avoid becoming pregnant while being treated with
Kyprolis.
The most common serious adverse reactions were pneumonia, acute
renal failure, pyrexia and congestive heart failure. The most
common adverse reactions (incidence of 30 percent or greater)
observed in clinical trials of patients with multiple myeloma were
fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea and
pyrexia. Serious adverse reactions were reported in 45 percent of
patients.
Full prescribing information is available 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 biologics manufacturing 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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forward-looking statements that are based on the current
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and are subject to a number of risks, uncertainties and assumptions
that could cause actual results to differ materially from those
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noted, Amgen is providing this information as of July 23, 2015, and expressly disclaims any duty
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No forward-looking statement can be guaranteed and actual
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or identification of new product candidates or development of new
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In addition, sales of Amgen's products (including products of
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CONTACT: Amgen, Thousand
Oaks
Kristen Davis, 805-447-3008
(media)
Trish Hawkins, 805-447-5631
(media)
Arvind Sood, 805-447-1060
(Investors)
1.
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Dimopoulos, MA and
Terpos E. Multiple Myeloma. Annals of Oncology 21
(Supplement 7): vii143–vii150, 2010.
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Leukemia &
Lymphoma Society. Facts 2014-2015. Available at:
http://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/generalcancer/pdf/facts.pdf
Accessed July 2015.
|
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