ERBITUX(R) (Cetuximab) Receives Approval in Japan for Use in Advanced Colorectal Cancer
2008-07-16 07:34:00
ERBITUX Is First EGFR-Targeted Monoclonal Antibody Cancer Therapy
Approved for Use in Japan
NEW YORK–(EMWNews)–ImClone Systems Incorporated (NASDAQ: IMCL), a global leader in the
development and commercialization of novel antibodies to treat cancer,
today announced that ERBITUX®
(cetuximab) has received marketing authorization in Japan for use in
treating patients with advanced or metastatic colorectal cancer (mCRC).
Specifically, this approval allows for the use of ERBITUX to treat
patients with epidermal growth factor receptor (EGFR)-positive,
curatively unresectable (inoperable), advanced or recurrent CRC, and
allows the use of ERBITUX plus irinotecan in second and further lines of
mCRC. With this approval, ERBITUX is the first ever EGFR-targeted
monoclonal antibody to be submitted for and receive marketing
authorization in Japan.
“This approval is a major milestone for
ImClone, first and foremost because we and our ERBITUX partners Merck
KGaA and Bristol-Myers Squibb are now able to provide a new treatment
option to cancer patients in Japan, where colorectal cancer is one of
the fastest growing and most prevalent disease threats to both men and
women,” said John H. Johnson, Chief Executive
Officer of ImClone. “ImClone is committed to
maximizing the potential of ERBITUX as an effective therapy for patients
around the world with various types of cancer. We look forward to
broadening its approved use in Japan to include earlier lines of
treatment of colorectal cancer as well as other cancers in the future.”
Merck Ltd. Japan submitted an application to Japan’s
Ministry of Health, Labor and Welfare last year for the use of ERBITUX
in treating patients with EGFR-expressing mCRC. The submission was
mainly based on results from six different international studies
including trials conducted in Europe and Japan which confirm the
activity of ERBITUX in patients with mCRC. ImClone, Bristol-Myers
Squibb, and Merck Serono Co., Ltd., (along with the Japanese
subsidiaries of Merck LTD and Bristol-Myers Squibb) entered into a
co-development and co-commercialization agreement to jointly develop and
market ERBITUX in Japan for the treatment of EGFR-expressing mCRC, as
well as for the treatment of any other cancers the three companies agree
to pursue.
Bristol-Myers Squibb and Merck KGaA will utilize their respective sales
forces in Japan to make ERBITUX available to patients with mCRC. Under
the terms of the co-development and co-commercialization agreement of
ERBITUX in Japan, Merck Serono Co., Ltd. will distribute the product and
record the sales for the collaboration. The terms of this agreement
provide that Merck KGaA will receive 50 percent of the profit/loss from
sales in Japan, and ImClone and Bristol-Myers Squibb will each receive
25 percent. The sharing of profit/loss reflects the co-exclusive rights
to ERBITUX in Japan previously granted by ImClone to Merck KGaA and
Bristol-Myers Squibb. In addition to its percentage of profits, ImClone
will receive from Merck KGaA a 4.75 percent royalty of total net sales
in Japan.
About Colorectal Cancer
In Japan, the incidence of colorectal cancer has increased markedly
during the last 50 years. Among men and women in Japan, the incidence is
higher than for lung cancer (95,651 per year versus 66,453) and second
to stomach cancer (95,651 per year versus 109,779). In terms of
mortality, the ranking is slightly different; colorectal cancer is now
the third largest cancer threat in Japan after lung and stomach cancer
(38,206, 56,367 and 54,423 people per year, respectively). Approximately
25 percent of colorectal cancer patients present with metastatic disease
or cancer that has spread to other organs. EGFR is expressed in 60-80
percent of colorectal cancer tumors.
About ERBITUX®
(Cetuximab)
ERBITUX (cetuximab) is a monoclonal antibody (IgG1 Mab) designed to
inhibit the function of a molecular structure expressed on the surface
of normal and tumor cells called the epidermal growth factor receptor
(EGFR, HER1, c-ErbB-1). In vitro assays and in vivo animal
studies have shown that binding of ERBITUX to the EGFR blocks
phosphorylation and activation of receptor-associated kinases, resulting
in inhibition of cell growth, induction of apoptosis, and decreased
matrix metalloproteinase and vascular endothelial growth factor
production. In vitro, ERBITUX can mediate antibody-dependent
cellular cytotoxicity (ADCC) against certain human tumor types. In
vitro assays and in vivo animal studies have shown that
ERBITUX inhibits the growth and survival of tumor cells that express the
EGFR. No anti-tumor effects of ERBITUX were observed in human tumor
xenografts lacking EGFR expression.
Squamous Cell Carcinoma of the Head
and Neck (SCCHN)
ERBITUX, in combination with radiation therapy, is indicated for the
initial treatment of locally or regionally advanced squamous cell
carcinoma of the head and neck. ERBITUX, as a single agent, is indicated
for the treatment of patients with recurrent or metastatic squamous cell
carcinoma of the head and neck for whom prior platinum-based therapy has
failed.
Colorectal Cancer
ERBITUX, as a single agent, is indicated for the treatment of
EGFR-expressing metastatic colorectal cancer after failure of both
irinotecan- and oxaliplatin-based regimens. ERBITUX, as a single agent,
is also indicated for the treatment of EGFR-expressing metastatic
colorectal cancer in patients who are intolerant to irinotecan-based
regimens.
ERBITUX, in combination with irinotecan, is indicated for the treatment
of EGFR-expressing metastatic colorectal carcinoma in patients who are
refractory to irinotecan-based chemotherapy. The effectiveness of
ERBITUX in combination with irinotecan is based on objective response
rates. Currently, no data are available that demonstrate an improvement
in disease-related symptoms or increased survival with ERBITUX in
combination with irinotecan for the treatment of EGFR-expressing
metastatic colorectal carcinoma.
For full prescribing information, including boxed WARNINGS regarding
infusion reactions and cardiopulmonary arrest, visit http://www.ERBITUX.com.
IMPORTANT SAFETY INFORMATION
Grade 3/4 infusion reactions occurred in approximately 3% of patients
receiving ERBITUX (Cetuximab) in clinical trials, with fatal outcome
reported in less than 1 in 1000. Serious infusion reactions,
requiring medical intervention and immediate, permanent discontinuation
of ERBITUX, included rapid onset of airway obstruction (bronchospasm,
stridor, hoarseness), hypotension, loss of consciousness, and/or cardiac
arrest. Most reactions (90%) were associated with the first
infusion of ERBITUX despite premedication with antihistamines. Caution
must be exercised with every ERBITUX infusion, as there were patients
who experienced their first severe infusion reaction during later
infusions. Monitor patients for 1 hour following ERBITUX
infusions in a setting with resuscitation equipment and other agents
necessary to treat anaphylaxis (eg, epinephrine, corticosteroids,
intravenous antihistamines, bronchodilators, and oxygen). Longer
observation periods may be required in patients who require treatment
for infusion reactions.
Cardiopulmonary arrest and/or sudden death occurred in 4 (2%) of 208
patients with squamous cell carcinoma of the head and neck treated with
radiation therapy and ERBITUX, as compared to none of 212 patients
treated with radiation therapy alone. Fatal events occurred
within 1 to 43 days after the last ERBITUX treatment. Carefully
consider the use of ERBITUX in combination with radiation therapy in
head and neck cancer patients with a history of coronary artery disease,
congestive heart failure or arrhythmias in light of these risks. Closely
monitor serum electrolytes including serum magnesium, potassium, and
calcium during and after ERBITUX therapy.
Interstitial lung disease (ILD), which was fatal in one case, occurred
in 4 of 1570 (<0.5%) patients receiving ERBITUX in clinical trials.
Interrupt ERBITUX for acute onset or worsening of pulmonary symptoms.
Permanently discontinue ERBITUX where ILD is confirmed.
In clinical studies of ERBITUX, dermatologic toxicities, including
acneform rash, skin drying and fissuring, paronychial inflammation,
infectious sequelae (eg, S. aureus sepsis, abscess formation,
cellulitis, blepharitis, cheilitis), and hypertrichosis, occurred in
patients receiving ERBITUX therapy. Acneform rash occurred in 76-88% of
1373 patients receiving ERBITUX in clinical trials. Severe acneform rash
occurred in 1-17% of patients. Acneform rash usually developed within
the first two weeks of therapy and resolved in a majority of the
patients after cessation of treatment, although in nearly half, the
event continued beyond 28 days. Monitor patients receiving ERBITUX for
dermatologic toxicities and infectious sequelae. Sun exposure may
exacerbate these effects.
The safety of ERBITUX in combination with radiation therapy and
cisplatin has not been established. Death and serious
cardiotoxicity were observed in a single-arm trial with ERBITUX,
radiation therapy, and cisplatin (100 mg/m2)
in patients with locally advanced squamous cell carcinoma of the head
and neck. Two of 21 patients died, one as a result of pneumonia
and one of an unknown cause. Four patients discontinued treatment
due to adverse events. Two of these discontinuations were due to cardiac
events.
Hypomagnesemia occurred in 55% (199/365) of patients receiving
ERBITUX and was severe (NCI CTC grades 3 & 4) in 6-17%. The
onset of hypomagnesemia and accompanying electrolyte abnormalities
occurred days to months after initiation of ERBITUX therapy. Monitor
patients periodically for hypomagnesemia, hypocalcemia and hypokalemia,
during, and for at least 8 weeks following the completion of, ERBITUX
therapy. Replete electrolytes as necessary.
The overall incidence of late radiation toxicities (any grade) was
higher with ERBITUX in combination with radiation therapy compared with
radiation therapy alone. The following sites were affected: salivary
glands (65%/56%), larynx (52%/36%), subcutaneous tissue (49%/45%),
mucous membranes (48%/39%), esophagus (44%/35%), and skin (42%/33%) in
the ERBITUX and radiation versus radiation alone arms, respectively. The
incidence of grade 3 or 4 late radiation toxicities were similar between
the radiation therapy alone and the ERBITUX plus radiation therapy arms.
In women of childbearing potential, appropriate contraceptive
measures must be used during treatment with ERBITUX and for 6 months
following the last dose of ERBITUX. ERBITUX should only be used during
pregnancy if the potential benefit justifies the potential risk to the
fetus.
The most serious adverse reactions associated with ERBITUX across
all studies were infusion reactions, cardiopulmonary arrest,
dermatologic toxicity and radiation dermatitis, sepsis, renal failure,
interstitial lung disease, and pulmonary embolus.
The most common adverse reactions associated with ERBITUX (incidence
(>=)25%) are cutaneous adverse reactions (including rash, pruritus, and
nail changes), headache, diarrhea, and infection.
The most frequent adverse events seen in patients with carcinomas of the
head and neck receiving ERBITUX in combination with radiation therapy
(n=208) versus radiation alone (n=212) (incidence ≥50%)
were acneform rash (87%/10%), radiation dermatitis (86%/90%), weight
loss (84%/72%), and asthenia (56%/49%). The most common grade 3/4
adverse events ((>=)10%) included: radiation dermatitis (23%), acneform
rash (17%), and weight loss (11%).
The most frequent adverse events seen in patients with metastatic
colorectal cancer (n=288) in the ERBITUX + best supportive care arm
(incidence ≥ 50%) were fatigue (89%),
rash/desquamation (89%), abdominal pain (59%), and pain-other (51%). The
most common grade 3/4 adverse events ((>=)10%) included: fatigue (33%),
pain-other (16%), dyspnea (16%), abdominal pain (14%), infection without
neutropenia (13%), rash/desquamation (12%), and gastrointestinal-other
(10%).
The most frequent adverse events seen in patients with metastatic
colorectal cancer (n=354) treated with ERBITUX plus irinotecan in
clinical trials (incidence ≥ 50%) were
acneform rash (88%), asthenia/malaise (73%), diarrhea (72%), and nausea
(55%). The most common grade 3/4 adverse events ((>=) 10%) included:
diarrhea (22%), leukopenia (17%), asthenia/malaise (16%), and acneform
rash (14%).
About ImClone Systems
ImClone Systems Incorporated is a fully integrated global
biopharmaceutical company committed to advancing oncology care by
developing and commercializing a portfolio of targeted biologic
treatments designed to address the medical needs of patients with a
variety of cancers. The Company’s research
and development programs include growth factor blockers and angiogenesis
inhibitors. ImClone Systems’ headquarters and
research operations are located in New York City, with additional
administration and manufacturing facilities in Branchburg, New Jersey.
For more information about ImClone Systems, please visit the Company’s
web site at http://www.imclone.com.
ERBITUX is a registered trademark of ImClone Systems Incorporated.
Certain matters discussed in this news release may constitute
forward-looking statements within the meaning of the Private Securities
Litigation Reform Act of 1995 and the Federal securities laws. Although
the company believes that the expectations reflected in such
forward-looking statements are based upon reasonable assumptions it can
give no assurance that its expectations will be achieved.
Forward-looking information is subject to certain risks, trends and
uncertainties that could cause actual results to differ materially from
those currently expected. Many of these factors are beyond the company’s
ability to control or predict. Important factors that may cause actual
results to differ materially and could impact the company and the
statements contained in this news release can be found in the company’s
filings with the Securities and Exchange Commission, particularly those
factors identified as “risk factors”
in the Company’s most recent annual report of
Form 10-K and in its quarterly reports on Form 10-Q and current reports
on Form 8-K. For forward-looking statements in this news release, the
company claims the protection of the safe harbor for forward-looking
statements contained in the Private Securities Litigation Reform Act of
1995. The company assumes no obligation to update or supplement any
forward-looking statements whether as a result of new information,
future events or otherwise.
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