NEW YORK, Sept. 11 /PRNewswire-FirstCall/ -- ImClone Systems
Incorporated (Nasdaq: IMCL) and Bristol-Myers Squibb Company (NYSE: BMY)
today announced that a Phase III study of ERBITUX(R) (Cetuximab) in
combination with platinum-based chemotherapy (vinorelbine plus cisplatin)
met its primary endpoint of increasing overall survival compared with
chemotherapy alone in patients with advanced non-small cell lung cancer
(NSCLC). This large, randomized multi-national study, known as FLEX
(First-Line Treatment for Patients with Epidermal growth factor inhibitor
(EGFR)-EXpressing Advanced NSCLC) was conducted by Merck KGaA, Darmstadt,
Germany and enrolled patients with Stage IIIB or Stage IV NSCLC who had not
previously received chemotherapy.
"Based on the FLEX results, ERBITUX is the only member of the class of
epidermal growth factor inhibitors to demonstrate survival in the
first-line treatment of patients with advanced non-small cell lung cancer.
Previous pivotal trials involving other agents targeting EGFR have failed
to demonstrate a survival advantage for these patients," stated Eric K.
Rowinsky, M.D., Chief Medical Officer and Senior Vice President of ImClone
Systems. "These are important results for lung cancer patients and health
care professionals treating this devastating disease, since there have been
very few treatment advances for lung cancer in recent years."
"Studies have shown that ERBITUX improves overall survival for patients
with certain head and neck cancers, and now, with the FLEX data, for
patients with advanced non-small cell lung cancer," said Martin Birkhofer,
M.D., Vice President, Oncology Global Medical Affairs, Bristol-Myers
Squibb. "We look forward to sharing these data with the medical community."
Results from this study will be submitted for presentation at an
upcoming medical conference.
Merck KGaA, Darmstadt, Germany, is ImClone Systems' ERBITUX partner
outside of North America.
About Lung Cancer
The American Cancer Society estimates that in the U.S., more than
213,000 people will be diagnosed with lung cancer in 2007. Lung cancer is
the leading cause of cancer-related death in men and women in the U.S.,
with 160,000 deaths estimated in 2007. Approximately 80 to 85% of these
patients will be diagnosed with non-small cell lung cancer, with the
majority being diagnosed with locally advanced or metastatic disease.
About ERBITUX(R) (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's 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.
ERBITUX (Cetuximab), 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
(Cetuximab) therapy. These reactions are characterized by rapid onset of
airway obstruction (bronchospasm, stridor, hoarseness), urticaria,
hypotension, loss of consciousness, 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, inflammatory and infectious
sequelae (eg, blepharitis, cheilitis, cellulitis, cyst), and hypertrichosis
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).
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. If ERBITUX is used during pregnancy or if patients
become pregnant while receiving ERBITUX , patients should be apprised of
the potential risk for loss of pregnancy or potential hazard to the fetus.
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 a fully integrated 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(R) 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 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. There can be
no guarantee that a registrational submission will be made to the FDA based
on the data described in this press release or if such registrational
submission is made, that it would receive FDA approval. 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.
SOURCE ImClone Systems Incorporated; Bristol-Myers Squibb Company
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Related links:
http://www.imclone.com
http://www.bms.com http://www.ERBITUX.com
CONTACT:
Media and Investors, ImClone Systems
Incorporated, Rebecca Gregory, +1-646-638-5058,
Rebecca.Gregory@imclone.com, or Tracy Henrikson, +1-908-243-9945,
Tracy.Henrikson@imclone.com, both of Corporate Communications,
ImClone Systems Incorporated; or Bristol-Myers Squibb, Media,
Madeline Malia, +1-609-252-3347, Madeline.Malia@bms.com, or Tony
Plohoros, +1-609-252-7938, Tony.Plohoros@bms.com, or Investors,
John Elicker, +1-212-546-3775, John.Elicker@bms.com, all of
Bristol-Myers Squibb
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