Vectibix(R) Approved in the European Union for the Treatment of Metastatic Colorectal Cancer
Clinically Relevant Biomarker Provides Physicians With the Ability
to Predict the Patients Most Likely to Respond to Vectibix Treatment
THOUSAND OAKS, Calif.--(BUSINESS WIRE)--Dec. 5, 2007--Amgen
(NASDAQ: AMGN) today announced that the European Commission has
granted a conditional marketing authorization for Vectibix(R)
(panitumumab) as monotherapy for the treatment of patients with
epidermal growth factor receptor (EGFr) expressing metastatic
colorectal cancer (mCRC) with non-mutated (wild-type) KRAS genes after
failure of standard chemotherapy regimens.
Vectibix, a fully human anti-EGFr monoclonal antibody, has been
granted a positive Commission decision in the European Union (EU)
based upon a positive opinion from the European Committee for
Medicinal Products for Human Use (CHMP) for marketing authorization in
September of this year. This approval is based on a positive benefit /
risk assessment in a patient population that currently has few
treatment options available to them. As part of the CHMP review,
clinical data supporting the utility of KRAS mutation status as a
biomarker for clinical outcome were provided.
"It is an exciting time in the oncology arena as we see a shift
towards individualized patient care," said Willard Dere, M.D., senior
vice president and international chief medical officer at Amgen. "We
are pleased that Vectibix has received conditional marketing
authorization allowing metastatic colorectal cancer patients to have
access to a new targeted treatment option."
These biomarker data were generated from a prospectively defined
analysis of the Phase 3, randomized, controlled clinical trial "408"
that investigated the treatment effect of KRAS status (non-mutated
versus mutated) in Vectibix patients with mCRC. The analysis
demonstrated that the effect of Vectibix on progression-free survival
(PFS) was confined exclusively to the approximately 60 percent of
patients whose tumors harbor normal, non-mutated (wild-type) KRAS.
Vectibix had no clinical benefit in patients who had tumors with
mutations in KRAS regardless of the endpoint studied. Previously
reported pivotal results from "408" demonstrated that Vectibix
monotherapy significantly improved PFS and response rates in heavily
pre-treated patients with mCRC after failure of standard chemotherapy
versus best supportive care.
KRAS plays an important role in cell growth regulation and
oncogenesis. Anti-EGFr therapies work by blocking the activation of
EGFr, thereby inhibiting downstream events that lead to malignant
signaling. However, in patients with tumors harboring a mutated or
activated KRAS, the KRAS protein is always turned "on" regardless of
whether EGFr has been activated or therapeutically inhibited. Thus, in
patients with mutated KRAS, signaling continues despite anti-EGFr
therapy. Mutant KRAS is detected in approximately 40 percent of CRC
"Being able to select which patients are more likely to respond to
therapy is an important step forward in the treatment of metastatic
colorectal cancer," said Professor Eric Van Cutsem, Digestive Oncology
Unit, University Hospital, Leuven, Belgium, a Vectibix investigator.
"The ability to predict the patient population more likely to respond
to Vectibix could potentially reduce drug exposure in patients who we
know will not respond."
Vectibix, the first fully human IgG2 monoclonal antibody (MAb)
therapy, targets the EGFr, a protein that plays an important role in
cancer cell signaling. With its demonstrated efficacy and convenient
Q2W dosing schedule Vectibix provides an important option in the
management of mCRC patients. Ongoing Phase 3 trials are exploring the
potential of administering Vectibix in combination with chemotherapy
in the first- and second-line of mCRC, as well as in the head and neck
In the EU, Vectibix is indicated as monotherapy for the treatment
of patients with metastatic colorectal carcinoma expressing EGFr with
tumors with non-mutated KRAS and after failure of fluoropyrimidine-,
oxaliplatin-, and irinotecan-containing chemotherapy regimens.
Approved by the Food and Drug Administration (FDA) in September
2006, Vectibix is indicated in the United States (U.S.) as a single
agent for the treatment of patients with EGFr-expressing, metastatic
colorectal carcinoma 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, metastatic colorectal carcinoma is based
on progression-free survival. Currently, no data are available that
demonstrate an improvement in disease-related symptoms or increased
survival with Vectibix.
Important Product Safety Information - EU
Dermatologic related reactions, a pharmacologic effect observed
with epidermal growth factor receptor (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 promptly initiated.
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 90 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
one 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.
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Sabeena Ahmad, +41 41 3692 530 (EU media)
Christine Regan, 805-447-5476 (U.S. media)
Arvind Sood, 805-447-1060 (investors)