Amgen (ticker: AMGN, exchange: NASDAQ Global Market (.O))
News Release -
KRAS Biomarker Analysis from Pivotal Vectibix(TM) Trial PublishedManuscript Data Delineate Potential Role of KRAS Oncogene in Patient Selection for Vectibix Treatment
THOUSAND OAKS, Calif., Mar 04, 2008 (BUSINESS WIRE) -- Amgen (NASDAQ: AMGN) today announced that the results from a
biomarker analysis of the pivotal "408" trial were published in the
Journal of Clinical Oncology (JCO). The analysis showed that KRAS
mutations could be used to identify patients who may not respond to
treatment with Vectibix(TM) (panitumumab) monotherapy, the first fully
human anti-epidermal growth factor receptor (EGFr) monoclonal
antibody. These data were previously reported at the European Cancer
Conference in 2007 and the Gastrointestinal Cancer Symposium in
January 2008. The paper was made available early online on the JCO Web
site and will be in the April 2008 print edition.
These findings are the first published results from a Phase 3
randomized, controlled clinical trial to affirm the link between
non-mutated (wild-type) KRAS in tumors, and the efficacy of treatment
with anti-EGFr in patients with metastatic colorectal cancer (mCRC).
The analysis met primary and secondary endpoints by demonstrating that
the effect of Vectibix on progression-free survival (PFS) was
different in patients according to the mutational status of the KRAS
gene in their tumors. The effect of Vectibix on PFS and response rate
appeared to be confined exclusively to the patients whose tumors
harbor normal, non-mutated KRAS.
"These results validate the importance of the KRAS oncogene in
identifying appropriate patients for treatment with Vectibix
monotherapy in the advanced colorectal cancer setting," said Roger M.
Perlmutter, M.D., Ph.D., executive vice president of Research and
Development at Amgen. "We have developed the first prospective
clinical trials with KRAS in earlier lines of mCRC to enhance our
understanding of this biomarker and its potential application. We also
are continuing to investigate the role of other markers to further
refine patient selection."
These analyses were derived from the pivotal "408" trial, which
had shown that Vectibix monotherapy was significantly more effective
than best supportive care in treating mCRC patients in the
chemorefractory setting. Activating KRAS mutations were detected using
real-time polymerase chain reaction (PCR) on DNA derived mostly from
fixed, archived tumor sections.
Results from studies performed over the last twenty-five years
indicate that KRAS plays an important role in cell growth regulation.
In mCRC, the 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.
Anti-EGFr therapies work by blocking the activation of EGFr, thereby
inhibiting downstream events that lead to malignant signaling.
However, it is hypothesized that in patients with tumors harboring a
mutated KRAS gene, the KRAS protein is always turned "on," regardless
of whether the EGFr has been activated or therapeutically inhibited.
Vectibix was approved in the United States (U.S.) in September
2006 as a single agent 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 PFS. Currently
no data are available that demonstrate an improvement in
disease-related symptoms or increased survival with Vectibix. In the
U.S., Vectibix is not approved for use based on KRAS status. In
December 2007, the European Medicines Agency (EMEA) granted a
conditional marketing authorization for Vectibix as monotherapy for
the treatment of patients with EGFr expressing mCRC with non-mutated
KRAS genes after failure of standard chemotherapy regimens. Regulatory
applications in the rest of the world are still pending.
There are currently ongoing Phase 3 trials examining Vectibix in
combination with chemotherapy in the first- and second-line of mCRC.
KRAS and other biomarker analyses have and will continue to be
integrated into the ongoing clinical program studying Vectibix in
earlier lines of mCRC therapy in combination with chemotherapy, as
well as in other tumor types.
Important Product Safety Information - U.S.
Dermatologic toxicities, related to Vectibix blockade of EGF
binding and subsequent inhibition of EGF receptor-mediated signaling
pathways, included but were not limited to dermatitis acneiform,
pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and
skin fissures. Dermatologic toxicities were reported in 89 percent of
patients treated with Vectibix and were severe in 12 percent of
patients. Severe dermatologic toxicities were complicated by
infection, including sepsis, septic death, and abscesses requiring
incisions and drainage. Vectibix may need to be withheld or
discontinued for severe dermatologic toxicities.
Severe infusion reactions occurred with Vectibix in approximately
1 percent of patients. Severe infusion reactions were identified as
anaphylactic reactions, bronchospasm, fever, chills, and hypotension.
Although fatal infusion reactions have not been reported with
Vectibix, they have occurred with other monoclonal antibody products.
Severe infusion reactions require stopping the infusion and possibly
permanently discontinuing Vectibix, depending on the severity and/or
persistence of the reaction.
Important Product Safety Information - European Union
Dermatologic related reactions, a pharmacologic effect observed
with EGFr inhibitors, are experienced with nearly all patients
(approximately 90 percent) treated with Vectibix. The majority of
dermatological reactions are mild to moderate in nature. In clinical
studies, subsequent to the development of severe dermatological
reactions (including stomatitis), infectious complications including
sepsis, in rare cases leading to death, and local abscesses requiring
incisions and drainage were reported. Patients who have severe
dermatologic reactions or who develop worsening reactions whilst
receiving Vectibix should be monitored for the development of
inflammatory or infectious sequelae, and appropriate treatment
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Christine Regan, 805-447-5476 (media)
Arvind Sood, 805-447-1060 (investors)