Phase
3 Trial Comparing Vectibix® (Panitumumab) to Erbitux® (Cetuximab) Meets Primary
Endpoint Of Non-Inferiority Of Overall Survival. Trial Evaluated Nearly 1,000 Patients
With Metastatic Colorectal Cancer
Full
press release follows.
SOURCE:
Amgen
THOUSAND
OAKS, Calif., Sept. 28, 2013 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today
announced detailed results from the Phase 3 ASPECCT ('763) trial comparing
Vectibix® (panitumumab) to Erbitux® (cetuximab) for the
treatment of wild-type KRAS metastatic colorectal cancer in patients who
have not responded to chemotherapy. The study met its primary endpoint,
demonstrating that panitumumab was non-inferior to cetuximab for overall
survival. The results were presented in an oral presentation at the 17th ECCO -
38th ESMO - 32nd ESTRO European Cancer Congress in Amsterdam (Abstract No. 18).
The
prospective study showed that the median overall survival for patients treated
with panitumumab was 10.4 months (range 9.4 months to 11.6 months) compared to
10 months (range 9.3 months to 11.0 months) for patients treated with cetuximab
(95 percent CI, 0.84-1.11, p=0.0007).
Colorectal
cancer is the second leading cause of cancer deaths.1,2
Approximately 1.2 million cases of colorectal cancer are expected to occur
globally.
"ASPECCT
was a well-conducted and robust Phase 3 trial involving nearly 1,000 patients
globally with metastatic colorectal cancer," said Sean E. Harper, M.D.,
executive vice president of Research and Development at Amgen. "Colorectal
cancer is a devastating disease and these results provide physicians with
important new information about the role Vectibix can play as they evaluate
treatment options."
In the
study, progression-free survival was a median of 4.1 months in patients treated
with panitumumab versus 4.4 months in patients treated with cetuximab (HR=1.00,
95 percent CI, 0.88, 1.14). Objective response rate, which is the percentage of
patients who experienced tumor size reduction, was 22 percent for patients
treated with panitumumab compared to 19.8 percent for patients in the cetuximab
arm (Odds Ratio 1.15, 95 percent CI, 0.83, 1.58).
In the
safety analysis, the profiles of both treatments were consistent with
previously reported studies. Adverse events (AEs) included known events such as
rash, low levels of magnesium in the blood and infusion reactions.
In
Europe, the ASPECCT trial is a Specific Obligation for Vectibix as part of the
European Medicine Agency's (EMA) conditional marketing authorization.
ASPECCT
('763) Trial Design
ASPECCT
is a global, randomized, multicenter, open-label, Phase 3 non-inferiority trial
designed to compare the effect of panitumumab versus cetuximab on overall
survival for monotherapy treatment of chemorefractory metastatic colorectal
cancer (mCRC) in 999 patients with wild-type KRAS tumors (primary
endpoint). Secondary endpoints included safety, patient reported outcomes,
progression-free survival, time to response, time to treatment failure and
duration of response.
Patients
were randomized in a 1:1 ratio to receive 6 mg/kg of intravenous panitumumab
every 14 days or 400 mg/m2 of an initial dose of intravenous
cetuximab, followed by 250 mg/m2 of intravenous cetuximab every
seven days.
About KRAS
Results
from studies performed over the last 30 years indicate that KRAS plays
an important role in cell growth regulation. In mCRC, EGFR transmits signals
through a set of intracellular proteins. Upon reaching the nucleus, these
signals instruct the cancer cell to reproduce and metastasize, leading to
cancer progression.3 Anti-EGFR antibody therapies work by inhibiting
the activation of EGFR, thereby inhibiting downstream events that lead to
malignant signaling. However, in patients whose tumors harbor a mutated KRAS
gene, the KRAS protein is always turned "on," regardless of whether
the EGFR has been activated or therapeutically inhibited. Common KRAS
mutations occurring in exon 2 (codons 12/13) are present in approximately 40 to
50 percent of mCRC patients.4,5
About
Vectibix
Vectibix
is the first fully human anti-EGFR antibody approved by the United States
(U.S.) Food and Drug Administration (FDA) for the treatment of mCRC. Vectibix
was approved in the U.S. in September 2006 as a monotherapy for the treatment
of patients with EGFR-expressing mCRC after disease progression on or following
fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy
regimens.
The
effectiveness of Vectibix as a single agent for the treatment of
EGFR-expressing mCRC is based on progression-free survival. Currently no data
are available that demonstrate an improvement in disease-related symptoms or
increased survival with Vectibix.
Retrospective
subset analyses of mCRC trials have not shown a treatment benefit for Vectibix
in patients whose tumors had RAS mutations. In the EU, the use of
Vectibix is not recommended for the treatment of colorectal cancer with these
mutations.
Important
U.S. Product Information
Vectibix
is indicated as a single agent for the treatment of EGFR-expressing mCRC with
disease progression on or following fluoropyrimidine-, oxaliplatin- and
irinotecan-containing chemotherapy regimens. The effectiveness of Vectibix as a
single agent for the treatment of EGFR-expressing mCRC is based on
progression-free survival. Currently, no data demonstrate an improvement in
disease-related symptoms or increased survival with Vectibix.
Vectibix
is not indicated for the treatment of patients with KRAS
mutation-positive mCRC or for whom KRAS mCRC status is unknown.
Retrospective subset analyses of metastatic colorectal cancer trials have not
shown a treatment benefit for Vectibix in patients whose tumors had KRAS
mutations in codon 12 or 13. Vectibix in combination with oxaliplatin-based
chemotherapy is not indicated for the treatment of patients with RAS (KRAS
or NRAS) mutation-positive mCRC or for whom RAS status is
unknown.
WARNING:
DERMATOLOGIC TOXICITY and INFUSION REACTIONS
Dermatologic
Toxicity: Dermatologic toxicities occurred in 89 percent of patients and were
severe (NCI-CTC grade 3 or higher) in 12 percent of patients receiving Vectibix
monotherapy. [See Dosage and Administration (2.1), Warnings and Precautions
(5.1), and Adverse Reactions (6.1)].
Infusion
Reactions: Severe infusion reactions occurred in approximately one percent of
patients. Fatal infusion reactions occurred in postmarketing experience [See
Dosage and Administration (2.1), Warnings and Precautions (5.2), and Adverse
Reactions (6.1, 6.3)].
The
most common adverse events of Vectibix are skin rash with variable
presentations, hypomagnesemia, paronychia, fatigue, abdominal pain, nausea and
diarrhea, including diarrhea resulting in dehydration.
The
most serious adverse reactions of Vectibix are pulmonary fibrosis, pulmonary
embolism, severe dermatologic toxicity complicated by infectious sequelae and
septic death, infusion reactions, abdominal pain, hypomagnesemia, nausea,
vomiting and constipation.
Important
EU Product Information
For
full prescribing information please see the Summary of Product Characteristics.
Vectibix
is indicated for the treatment of adult patients with wild-type RAS
metastatic colorectal cancer (mCRC):
• in first-line in combination with
FOLFOX.
• in second-line in combination with
FOLFIRI for patients who have received first-line fluoropyrimidine-based
chemotherapy (excluding irinotecan).
• as monotherapy after failure of
fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy
regimens.
Vectibix
is contraindicated in patients with a history of severe or life-threatening
hypersensitivity reactions to the product and in patients with interstitial
pneumonitis or pulmonary fibrosis.
The
combination of Vectibix with oxaliplatin-containing chemotherapy is
contraindicated for patients with mutant RAS mCRC or for whom RAS mCRC
status is unknown.
Other
adverse events of special importance associated with Vectibix and/or EGFR
monoclonal antibody therapies include dermatologic-related reactions, pulmonary
complications, electrolyte disturbances, infusion-related reactions (including
rare reports with fatal outcome) and ocular toxicities. These events should be
monitored carefully, see Summary of Product Characteristics for information on
appropriate management of these adverse events. Acute renal failure has been
observed in patients who develop severe diarrhoea and dehydration. For patients
with ECOG 2 performance status, assessment of benefit-risk is recommended prior
to initiation of Vectibix in combination with chemotherapy for treatment of
mCRC.
Vectibix
should not be used in combination with IFL [bolus 5-fluorouracil (500 mg/m2),
leucovorin (20 mg/m2) and irinotecan (125 mg/m2)] or in combination with
bevacizumab containing chemotherapy.
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 the world's largest independent biotechnology company,
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
This
news release contains forward-looking statements that are based on management's
current expectations and beliefs and are subject to a number of risks,
uncertainties and assumptions that could cause actual results to differ
materially from those described. All statements, other than statements of
historical fact, are statements that could be deemed forward-looking
statements, including estimates of revenues, operating margins, capital
expenditures, cash, other financial metrics, expected legal, arbitration,
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patterns or practices, reimbursement activities and outcomes and other such
estimates and results. Forward-looking statements involve significant
risks and uncertainties, including those discussed below and more fully
described in the Securities and Exchange Commission (SEC) reports filed
by Amgen, including Amgen's most recent annual report on Form
10-K and any subsequent periodic reports on Form 10-Q and Form 8-K. Please
refer to Amgen's most recent Forms 10-K, 10-Q and 8-K for additional
information on the uncertainties and risk factors related to our
business. Unless otherwise noted, Amgen is providing this
information as of Sept. 28, 2013, and expressly disclaims any duty to
update information contained in this news release.
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 indications for existing products cannot be
guaranteed and movement 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 guarantee safe and
effective performance of product candidates in humans. The complexity of the
human body cannot be perfectly, or 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
product marketing has in the past varied and we expect similar variability in
the future. We develop product candidates internally and through licensing
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become subject to significant sanctions. We depend on third parties for a
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In
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imposed by third-party payers, including governments, private insurance plans
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guideline developments and domestic and international trends toward managed
care and healthcare cost containment as well as U.S. legislation affecting
pharmaceutical pricing and reimbursement. Government and others' regulations
and reimbursement policies may affect the development, usage and pricing of our
products. In addition, we compete with other companies with respect to
some of our marketed products as well as for the discovery and development of
new products. We believe that some of our newer products, product
candidates or new indications for existing products, may face competition when
and as they are approved and marketed. Our products may compete against
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and technology, the protection offered by our patents and patent applications
may be challenged, invalidated or circumvented by our competitors and there can
be no guarantee of our ability to obtain or maintain patent protection for our
products or product candidates. We cannot guarantee that we will be able to
produce commercially successful products or maintain the commercial success of
our existing products. Our stock price may be affected by actual or perceived
market opportunity, competitive position, and success or failure of our
products or product candidates. Further, the discovery of significant problems
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and on our business and results of operations.
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 (FDA) for the products. The products are not approved for
the investigational use(s) discussed in this news release, and no
conclusions can or should be drawn regarding the safety or effectiveness of the
products for these uses.
Erbitux®
is a registered trademark of ImClone LLC.
CONTACT:
Amgen, Thousand Oaks
Christine Regan, 805-447-5476 (media)
Arvind Sood,
805-447-1060 (investors)
1 Cancer Facts and Figures 2013.
American Cancer Society website. http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-036845.pdf.
Accessed March 25, 2013.
2 Colorectal Cancer Prevention (PDQ®).
National Cancer Institute. Accessed March 25, 2013. http://www.cancer.gov/cancertopics/pdq/prevention/colorectal/HealthProfessional/page3.
3
Malumbres, M. and Barbacid, M. RAS oncogenes: the first 30 years. Nature
Reviews Cancer. 3:459-65, 2003.
4 Karapentis C, S.
Snell, L, E. The Laboratory Assessment of KRAS Mutation Status in
Colorectal Cancer. Asia Pacific Journal of Oncology and
Hematology. 2010.
5 Friday BB and Adjei AA. K-ras as a
target for cancer therapy. Biochim. Biophys. Acta 1756:
127-144, 2005.
SOURCE
Amgen
