NEW YORK and TOKYO, Feb. 5 /PRNewswire-FirstCall/ -- ImClone Systems
(Nasdaq: IMCL) and Bristol-Myers Squibb Company (NYSE: BMY) announced today
that an application has been submitted with the Japanese Pharmaceuticals
and Medical Devices Agency (PMDA) for the use of ERBITUX(R) (Cetuximab) in
treating patients with advanced colorectal cancer. ERBITUX is the first
IgG1 monoclonal antibody that inhibits the epidermal growth factor receptor
(EGFR) to be submitted for marketing authorization in Japan.
The Japanese submission was based on results from studies conducted in
Europe and Japan which confirm the activity of ERBITUX in patients with
metastatic colorectal cancer.
In Japan, the incidence of colorectal cancer has increased markedly
during the last 50 years(1). Among men and women in Japan, the incidence is
higher than for lung cancer (95,651 per year vs 66,453) and second to
stomach cancer (95,651 per year vs 109,779). In terms of mortality, the
ranking is slightly different: Colorectal cancer is now the third biggest
cancer threat in Japan after lung and stomach cancer (38,206, 56,367 and
54,423 people per year, respectively)(2). Approximately 25 percent of
colorectal cancer patients present with metastatic disease(3).
The filing in Japan is a result of a development collaboration between
ImClone Systems, Bristol-Myers Squibb, and Merck KGaA of Darmstadt,
Germany.
About ERBITUX (Cetuximab)
ERBITUX 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. While the mechanism of ERBITUX' anti-tumor effect(s) in vivo is
unknown, all of these processes may contribute to the overall therapeutic
effect of ERBITUX. EGFR is part of a signaling pathway that is linked to
the growth and development of many human cancers, including those of the
head and neck, colon and rectum.
In the U.S., ERBITUX, in combination with radiation therapy, is
indicated for the 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.
ERBITUX is indicated for the treatment of EGFR-expressing, metastatic
colorectal carcinoma (mCRC) in combination with irinotecan for patients who
are refractory to irinotecan-based chemotherapy, and as a single agent for
patients who are intolerant to irinotecan-based therapy. The effectiveness
of ERBITUX for the treatment of EGFR-expressing mCRC cancer is based on
objective response rates. Currently, no data are available that demonstrate
an improvement in disease-related symptoms or increased survival with
ERBITUX for the treatment of EGFR-expressing mCRC.
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, rarely with fatal outcome (<1 in 1000),
occurred in approximately 3% (46/1485) of patients receiving ERBITUX
therapy. These reactions are characterized by rapid onset of airway
obstruction (bronchospasm, stridor, hoarseness), urticaria, hypotension,
and/or cardiac arrest. Severe infusion reactions require immediate and
permanent discontinuation of ERBITUX therapy.
Most reactions (90%) were associated with the first infusion of ERBITUX
despite the use of prophylactic antihistamines. Caution must be exercised
with every ERBITUX infusion as there were patients who experienced their
first severe infusion reaction during later infusions. A 1-hour observation
period is recommended following the ERBITUX infusion. Longer observation
periods may be required in patients who experience infusion reactions.
Cardiopulmonary arrest and/or sudden death occurred in 2% (4/208) of
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. ERBITUX in combination with radiation
therapy should be used with caution in patients with known coronary artery
disease, congestive heart failure and arrhythmias. Close monitoring of
serum electrolytes, including serum magnesium, potassium, and calcium
during and after ERBITUX therapy is recommended.
Severe cases of interstitial lung disease (ILD), which was fatal in one
case, occurred in less than 0.5% of 774 patients with advanced colorectal
cancer (mCRC) receiving ERBITUX. There was one case of ILD reported in 796
patients with head and neck cancer receiving ERBITUX in clinical studies.
In clinical studies of ERBITUX, dermatologic toxicities, including
acneform rash, skin drying and fissuring, and inflammatory and infectious
sequelae (eg, blepharitis, cheilitis, cellulitis, cyst) were reported. In
208 patients receiving ERBITUX + RT, acneform rash was reported in 87% (17%
severe) as compared to 10% in 212 patients treated with radiation therapy
alone (1% severe). In patients receiving ERBITUX alone, 76% (N=103)
experienced acneform rash (1% severe). In patients with mCRC, acneform rash
was reported in 89% (686/774) of all treated patients, and was severe in
11% (84/774). Subsequent to the development of severe dermatologic
toxicities, complications including S. aureus sepsis and abscesses
requiring incision and drainage were reported. Sun exposure may exacerbate
these effects. A related nail disorder, occurring in 12% (0.4% Grade 3) of
patients, was characterized as a paronychial inflammation.
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, delayed, accelerated
(concomitant boost) fractionation radiation therapy, and cisplatin (100
mg/m2) conducted 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
(myocardial infarction in one patient and arrhythmia, diminished cardiac
output, and hypotension in the other patient).
The incidence of hypomagnesemia (both overall and severe [NCI CTC
Grades 3 & 4]) was increased in patients receiving ERBITUX alone or in
combination with chemotherapy as compared to those receiving best
supportive care or chemotherapy alone based on ongoing, controlled clinical
trials in 244 patients. Approximately one-half of these patients receiving
ERBITUX experienced hypomagnesemia and 10-15% experienced severe
hypomagnesemia. Electrolyte repletion was necessary in some patients and in
severe cases, intravenous replacement was required. Patients receiving
ERBITUX therapy should be periodically monitored for hypomagnesemia, and
accompanying hypocalcemia and hypokalemia during, and up to 8 weeks
following the completion of, ERBITUX therapy.
The most serious adverse reactions associated with ERBITUX in
combination with radiation therapy in 208 patients with head and neck
cancer were infusion reaction (3%), cardiopulmonary arrest (2%),
dermatologic toxicity (2.5%), mucositis (6%), radiation dermatitis (3%),
confusion (2%), and diarrhea (2%).
The most serious adverse reactions associated with ERBITUX in mCRC
clinical trials (N=774) were infusion reaction (3%), dermatologic toxicity
(1%), interstitial lung disease (0.4%), fever (5%), sepsis (3%), kidney
failure (2%), pulmonary embolus (1%), dehydration (5% in patients receiving
ERBITUX with irinotecan, 2% in patients receiving ERBITUX as a single
agent) and diarrhea (6% in patients receiving ERBITUX with irinotecan, 0.2%
in patients receiving ERBITUX as a single agent).
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%), skin (42%/33%), brain (11%/9%),
lung (11%/8%), spinal cord (4%/3%), and bone (4%/5%) in the ERBITUX and
radiation versus radiation alone arms, respectively.
The incidence of Grade 3 or 4 late radiation toxicities were generally
similar between the radiation therapy alone and the ERBITUX plus radiation
therapy arms.
The most common 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) were mucositis-stomatitis (93%/94%),
acneform rash (87%/10%), radiation dermatitis (86%/90%), weight loss
(84%/72%), xerostomia (72%/71%), dysphagia (65%/63%), asthenia (56%/49%),
nausea (49%/37%), constipation (35%/30%) and vomiting (29%/23%). The most
common adverse events seen in patients with carcinomas of the head and neck
receiving ERBITUX as a single agent (N=103) were acneform rash (76%),
asthenia (45%), pain (28%), fever (27%) and weight loss (27%).
The most common adverse events seen in patients with mCRC receiving
ERBITUX with irinotecan (n=354) or ERBITUX as a single agent (n=420) were
acneform rash (88%/90%), asthenia/malaise (73%/48%), diarrhea (72%/25%),
nausea (55%/29%), abdominal pain (45%/26%), vomiting (41%/25%), fever
(34%/27%), constipation (30%/26%), and headache (14%/26%).
About ImClone Systems
ImClone Systems Incorporated is committed to advancing oncology care by
developing 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' strategy is to become a fully
integrated biopharmaceutical company, taking its development programs from
the research stage to the market. ImClone Systems' headquarters and
research operations are located in New York City, with additional
administration and manufacturing facilities in Branchburg, New Jersey.
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 projected. 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, including quarterly
reports on Form 10-Q, current reports on Form 8-K and annual reports on
Form 10-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.
About Bristol-Myers Squibb
Bristol-Myers Squibb is dedicated to the discovery, development and
exhaustive exploration of innovative cancer fighting therapies designed to
extend and enhance the lives of patients living with cancer. More than 40
years ago, Bristol-Myers Squibb built a unified vision for the future of
cancer treatment. With expertise, dedication and resolve, that vision led
to the development of a diverse global portfolio of anti-cancer therapies
that are an important cornerstone of care today. Hundreds of scientists at
Bristol-Myers Squibb's Pharmaceutical Research Institute are studying ways
to improve current cancer treatments and identify better, more effective
medicines for the future.
Bristol-Myers Squibb is a global pharmaceutical and related health care
products company whose mission is to extend and enhance human life.
This press release contains "forward-looking statements" as that term
is defined in the Private Securities Litigation Reform Act of 1995
regarding product development. Such forward-looking statements are based on
current expectations and involve inherent risks and uncertainties,
including factors that could delay, divert or change any of them, and could
cause actual outcomes and results to differ materially from current
expectations. No forward-looking statement can be guaranteed. Among other
risks, there can be no guarantee that the application will be approved, or,
if approved, that the product will be commercially successful.
Forward-looking statements in this press release should be evaluated
together with the many uncertainties that affect Bristol-Myers Squibb's
business, particularly those identified in the cautionary factors
discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the
year ended December 31, 2006 and in our Quarterly Reports on Form 10-Q.
Bristol-Myers Squibb undertakes no obligation to publicly update any
forward-looking statement, whether as a result of new information, future
events or otherwise.
References:
1. Koyama Y, Kotake K. Overview of Colorectal Cancer in Japan: Report from
the Registry of the Japanese Society for Cancer of the Colon and
Rectum. Dis Colon Rectum. 1997; 40: S2-9.
2. Internacional Agency for Research on Cancer Web site. Available at:
http://www-dep.iarc.fr/ (Globocan 2002). Accessed on 2/2/2007.
3. Cunningham D et al. The Chemotherapy of Colon Cancer Can No Longer Be
Ignored. Eur J Cancer 1993; 29A: 2007-2079.
SOURCE ImClone Systems; Bristol-Myers Squibb Company
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Related links:
http://www.ERBITUX.com
CONTACT:
Andrea Rabney, Andrea.Rabney@imclone.com, or
David Pitts, David.Pitts@imclone.com, both Corporate
Communications of ImClone Systems Incorporated, +1-646-638-5058;
or Media: Madeline Malia, +1-609-252-3347,
Madeline.Malia@bms.com, or Tony Plohoros, +1-609-252-7938,
tony.plohoros@bms.com, or John Elicker, Investors,
+1-212-546-3775, John.Elicker@bms.com, all of Bristol-Myers
Squibb
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