THOUSAND OAKS, Calif.,
Jan. 15, 2015 /PRNewswire/ -- Amgen
(NASDAQ:AMGN) today announced new data from the Phase 2 PEAK and
Phase 3 PRIME studies that support the first-line use of
Vectibix® (panitumumab) in combination with FOLFOX, an
oxaliplatin-based chemotherapy regimen, in patients with wild-type
RAS (absence of exons 2, 3, or 4
KRAS or NRAS mutations) metastatic
colorectal cancer (mCRC). The data will be presented during a
poster session at the 2015 American Society of Clinical Oncology
(ASCO) Gastrointestinal Cancers Symposium taking place in
San Francisco from January 15 to 17.
In an exploratory analysis from the PEAK study (abstract #660),
treatment with Vectibix compared to bevacizumab
(Avastin®) resulted in a significantly higher proportion
of patients with earlier tumor shrinkage at week eight (64 percent
vs. 45 percent, respectively; 95 percent CI, p=0.0232), and
among responding patients, a significantly longer duration of
response (11.4 vs. 8.5 months, respectively; 95 percent CI,
p=0.0142) and greater depth of response (65 percent vs. 46
percent, respectively; p=0.0007). Overall response rates
(ORR) appeared to be similar between Vectibix and bevacizumab. This
is consistent with observed overall survival (OS) and
progression-free survival (PFS) rates, and with data previously
reported. The safety profile of Vectibix was consistent with
previously reported studies.
"These analyses help deepen our understanding of how Vectibix
works when added to a standard first-line chemotherapy for the
treatment of wild-type RAS metastatic colorectal cancer,"
said Sean E. Harper, M.D., executive
vice president of Research and Development at Amgen. "Our Vectibix
clinical trial program continues to yield new insights regarding
biomarkers and drug sequencing."
While the primary analysis from PEAK showed similar ORR between
the Vectibix- and bevacizumab-based regimens, this exploratory
analysis demonstrates that Vectibix produces early, sustained
anti-tumor activity, which may in part explain the OS and PFS
benefits seen with Vectibix versus bevacizumab in this trial.
A separate analysis from the Phase 3 PRIME study (abstract
#537), demonstrated that there were no significant differences in
quality of life among patients treated with Vectibix plus FOLFOX
versus FOLFOX alone despite the incidence of adverse events
associated with each treatment regimen. The quality of life
analysis included a scale that assessed mobility, self-care, usual
activities, pain/discomfort and anxiety/depression.
Colorectal cancer is the third most common cancer found in both
men and women in the U.S. and is the second leading cause of cancer
deaths.1,2 Approximately 1.2 million cases of colorectal
cancer are expected to occur globally each year.3
About the PEAK Study
The PEAK (Panitumumab Efficacy in Combination with mFOLFOX6 Against
bevacizumab plus mFOLFOX6 in mCRC subjects with wild-type
KRAS tumors) ('509) study is a global, multicenter,
randomized, interventional Phase 2 trial designed to compare
efficacy of first-line Vectibix (panitumumab) in combination with
mFOLFOX6 versus bevacizumab in combination with mFOLFOX6 in 285
previously untreated patients with wild-type KRAS exon 2
metastatic colorectal cancer (mCRC). Primary endpoints include
progression-free survival (PFS), and secondary endpoints include
overall survival (OS), percentage of patients with objective
response (OR), duration of response (DoR), depth of response (DpR)
and safety.
Patients were randomized in a 1:1 ratio to receive 6 mg/kg of
intravenous panitumumab and mFOLFOX6, or 5 mg/kg of intravenous
bevacizumab and mFOLFOX6 every 14 days.
In the exploratory analyses of tumor assessments, DpR was
defined as the percentage of tumor shrinkage at nadir (point in
time between chemotherapy cycles in which a patient experiences low
blood counts) or progression. Early tumor shrinkage (ETS) was
defined as the proportion of patients with >30 percent tumor
shrinkage at week eight.
About the PRIME Study
The PRIME (Panitumumab Randomized trial In combination with
chemotherapy for Metastatic colorectal cancer to determine
Efficacy) ('203) study is a global, multicenter, randomized Phase 3
study designed to evaluate Vectibix (panitumumab) in combination
with FOLFOX versus FOLFOX alone in 1,183 patients with wild-type
KRAS exon 2 metastatic colorectal cancer (mCRC). Primary
endpoints include progression-free survival (PFS), and secondary
endpoints include overall survival (OS), objective response rate
(ORR), duration of response (DoR) and safety.
Patients were randomized in a 1:1 ratio to receive 6 mg/kg of
panitumumab (day 1) and FOLFOX (day 1 and 2), or FOLFOX (day 1 and
2) alone of each 14-day cycle.
In this analysis, quality of life (QoL) was assessed every four
weeks until disease progression, and once at a safety follow-up,
using the EuroQoL 5-domain health state index and overall health
rating (OHR; 0-100 visual analogue scale).
About Vectibix® (panitumumab)
Vectibix is the first fully human anti-EGFR antibody approved by
the U.S. Food and Drug Administration (FDA) for the treatment of
metastatic colorectal cancer (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 after prior treatment with
fluoropyrimidine-, oxaliplatin-, and irinotecan-containing
chemotherapy.
In May 2014, the FDA approved
Vectibix for use in combination with FOLFOX, as first-line
treatment in patients with wild-type KRAS (exon 2) mCRC. With this
approval, Vectibix became the first- and- only biologic therapy
indicated for use with FOLFOX, one of the most commonly used
chemotherapy regimens, in the first-line treatment of mCRC for
patients with wild-type KRAS mCRC.
Important U.S. Product Information
Vectibix is indicated for the treatment of patients with wild-type
KRAS (exon 2 in codons 12 or 13) mCRC as determined by an
FDA-approved test for this use:
- As first-line therapy in combination with FOLFOX
- As monotherapy following disease progression after prior
treatment with fluoropyrimidine-, oxaliplatin-, and
irinotecan-containing chemotherapy
Vectibix is not indicated for the treatment of patients with
KRAS-mutant mCRC or for whom KRAS mutation status is
unknown. Vectibix in combination with oxaliplatin-based
chemotherapy is not indicated for the treatment of patients with
RAS-mutant mCRC or for whom RAS mutation status is unknown.
RAS is defined as exon 2 (codons 12 and 13), exon 3 (codons 59
and 61), and exon 4 (codons 117 and 146) of either KRAS or NRAS and
hereon is referred to as "RAS."
WARNING: DERMATOLOGIC TOXICITY
Dermatologic Toxicity: Dermatologic toxicities occurred in 90
percent of patients and were severe (NCI-CTC grade 3 or higher) in
15 percent of patients receiving Vectibix monotherapy. [See Dosage
and Administration (2.1), Warnings and Precautions (5.1), and
Adverse Reactions (6.1)]
A predefined retrospective subset analysis of a clinical study
further identified a shortening of progression-free survival (PFS)
and overall survival (OS) in patients with RAS-mutant tumors
who received Vectibix and FOLFOX versus FOLFOX alone.
Determination of RAS-mutant tumor status should be performed
by an experienced laboratory.
Determination of KRAS mutational status in colorectal
tumors using an FDA-approved test indicated for this use is
necessary for selection of patients for treatment with
Vectibix. Patients with KRAS-mutant mCRC tumors
receiving Vectibix in combination with FOLFOX experienced shorter
OS compared to FOLFOX alone.
Progressively decreasing serum magnesium levels leading to
severe (Grade 3-4) hypomagnesemia occurred in up to 7% of patients
across clinical trials. Monitor patients for hypomagnesemia
and hypocalcemia prior to initiating Vectibix treatment,
periodically during Vectibix treatment, and for up to 8 weeks
after the completion of treatment.
In a clinical trial, 4% of patients experienced infusion
reactions and 1% of patients experienced severe infusion reactions
(NCI-CTC grade 3-4).
Severe diarrhea and dehydration, leading to acute renal failure
and other complications, have been observed in patients treated
with Vectibix in combination with chemotherapy.
Fatal and non-fatal cases of interstitial lung disease (ILD)
(1%) and pulmonary fibrosis have been observed in patients treated
with Vectibix. Pulmonary fibrosis occurred in less than 1%
(2/1467) of patients enrolled in clinical studies of
Vectibix. In the event of acute onset or worsening of
pulmonary symptoms, interrupt Vectibix therapy. Discontinue
Vectibix therapy if ILD is confirmed.
The most common adverse reactions of Vectibix are skin rash with
variable presentations, paronychia, fatigue, nausea and diarrhea.
The most frequently reported serious, adverse reactions of Vectibix
are general physical health deterioration, and intestinal
obstruction.
The most commonly reported adverse reactions of Vectibix in
combination with FOLFOX are diarrhea, stomatitis, mucosal
inflammation, asthenia, paronychia, anorexia, hypomagnesemia,
hypokalemia, rash, acneiform dermatitis, pruritus, and dry skin.
The most frequently reported serious adverse reactions are diarrhea
and dehydration.
To see the full Vectibix Safety Information, visit
www.vectibix.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
This news release contains forward-looking statements that are
based on the current expectations and beliefs of Amgen Inc. and its
subsidiaries (Amgen, we or us) 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, political,
regulatory or clinical results or practices, customer and
prescriber 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 Inc.,
including Amgen Inc.'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 Inc.'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 Jan. 15, 2015,
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
and our partners 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 collaborations, partnerships and
joint ventures. Product candidates that are derived from
relationships may be subject to disputes between the parties or may
prove to be not as effective or as safe as we may have believed at
the time of entering into such relationship. Also, we or others
could identify safety, side effects or manufacturing problems with
our products after they are on the market. Our business may be
impacted by government investigations, litigation and product
liability claims. If we fail to meet the compliance obligations in
the corporate integrity agreement between us and the U.S.
government, we could become subject to significant sanctions. We
depend on third parties for a significant portion of our
manufacturing capacity for the supply of certain of our current and
future products and limits on supply may constrain sales of certain
of our current products and product candidate development.
In addition, sales of our products (including products of our
wholly-owned subsidiaries) are affected by the reimbursement
policies imposed by third-party payers, including governments,
private insurance plans and managed care providers and may be
affected by regulatory, clinical and 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
products that have lower prices, established reimbursement,
superior performance, are easier to administer, or that are
otherwise competitive with our products. In addition, while we and
our partners routinely obtain patents for our and their products
and technology, the protection of our products offered by patents
and patent applications may be challenged, invalidated or
circumvented by our or our partners' competitors and there can be
no guarantee of our or our partners' 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 with a product similar to one of our products
that implicate an entire class of products could have a material
adverse effect on sales of the affected products and on our
business and results of operations. Our efforts to integrate the
operations of companies we have acquired may not be successful.
Cost savings initiatives may result in us incurring impairment or
other related charges on our assets. We may experience
difficulties, delays or unexpected costs and not achieve
anticipated benefits and savings from our recently announced
restructuring plans. Our business performance could affect or limit
the ability of our Board of Directors to declare a dividend or our
ability to pay a dividend or repurchase common stock.
The scientific information discussed in this news release
related to our product candidates is preliminary and investigative.
Such product candidates are not approved by the U.S. Food and Drug
Administration, and no conclusions can or should be drawn regarding
the safety or effectiveness of the product candidates.
Avastin® is a registered trademark of Genentech,
Inc.
CONTACT: Amgen
Kristen Davis, 805-447-3008
(media)
Cuyler Mayer, 805-447-6332
(media)
Arvind Sood, 805-447-1060
(investors)
References
1 Colorectal Cancer Facts and
Figures. American Cancer Society website.
http://www.cancer.org/cancer/colonandrectumcancer/detailedguide/colorectal-cancer-key-statistics.
Accessed December 23, 2014.
2 Colorectal Cancer Prevention
(PDQ®). National Cancer Institute
website.
http://www.cancer.gov/cancertopics/pdq/prevention/colorectal/HealthProfessional/page3.
Accessed December 23, 2014.
3 Jemal. Global Cancer Statistics. CA Cancer J
Clin. 2011;61:69-90.
Logo -
http://photos.prnewswire.com/prnh/20081015/AMGENLOGO
To view the original version on PR Newswire,
visit:http://www.prnewswire.com/news-releases/amgen-presents-new-data-supporting-first-line-use-of-vectibix-panitumumab-in-combination-with-folfox-in-patients-with-wild-type-ras-metastatic-colorectal-cancer-300021446.html
SOURCE Amgen