Biotech News - ImClone Systems Incorporated (Public, NASDAQ:IMCL)

ImClone Systems Incorporated (Public, NASDAQ:IMCL)

Survival Data Available from Two Randomized ERBITUX Studies in
Metastatic Colorectal Cancer

- NCIC CTG study meets primary endpoint by significantly improving
overall survival -
- EPIC secondary endpoints strongly favor ERBITUX combination;
primary endpoint not met possibly due to post-study therapy -

NEW YORK, Nov. 6 ImClone Systems Incorporated (Nasdaq: IMCL - News)
and Bristol-Myers Squibb Company (NYSE: BMY - News) today announced
results from two randomized Phase III trials of ERBITUX® (cetuximab)
in patients with metastatic colorectal cancer. These are the first
large, randomized studies to examine the impact of ERBITUX treatment
on overall survival in colon cancer.

A randomized, multicenter, Phase III trial (NCIC CTG CO.17) compared
ERBITUX plus best supportive care to best supportive care alone in
572 patients with metastatic colorectal cancer whose disease was
refractory to all available chemotherapy, including irinotecan,
oxaliplatin, and fluoropyrimidines. The study, conducted by the
National Cancer Institute of Canada Clinical Trials Group (NCIC CTG)
in collaboration with the Australasian Gastro-Intestinal Trials
Group (AGITG), met its primary efficacy endpoint showing a
statistically significant improvement in overall survival. These are
the first data of an anticancer therapy to demonstrate overall
survival in this refractory treatment setting. The NCIC CTG is
scheduled to submit the data from this study for presentation at a
major medical meeting in 2007.

"This is the second tumor type where ERBITUX has shown survival
benefit," said Eric Rowinsky, M.D., Chief Medical Officer and Senior
Vice President of ImClone Systems. "Additionally, no other EGFR-
targeted therapy has demonstrated an improvement in overall survival
in a Phase III colorectal cancer clinical study."

A second Phase III, randomized study, known as the Erbitux Plus
Irinotecan in Colorectal Cancer (EPIC), compared irinotecan to
irinotecan plus ERBITUX in approximately 1,300 patients whose
disease was not responding to first-line oxaliplatin-based
chemotherapy. After randomization, patients were treated until their
disease progressed. Upon disease progression, study treatment was
stopped and further treatment was at the discretion of the physician.

Secondary efficacy endpoints (progression free survival, response
rate) strongly favored the combination of ERBITUX plus irinotecan
over irinotecan alone; however, the primary endpoint (overall
survival) was not met.

Efforts to interpret these confounded results are ongoing. A
preliminary review of the data reveal that a considerable number of
patients randomized to the irinotecan arm went on to receive ERBITUX
with or without irinotecan after failing irinotecan alone.

"The studies provide important new information for patients with
advanced colorectal cancer, and are part of our comprehensive
clinical development program designed to fully understand the
potential uses of ERBITUX for cancer patients," said Martin
Birkhofer, M.D., Vice President, Oncology Global Medical Affairs,
Bristol-Myers Squibb. "We look forward to our full analysis of the
data, and to sharing the results with the scientific community at a
major medical meeting."

"We are encouraged by the totality of the results from both studies
and we plan to have discussions with the Food and Drug
Administration concerning a registrational submission," said Eric
Rowinsky, M.D. Chief Medical Officer and Senior Vice President of
ImClone Systems.

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.

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, 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-am 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 Colorectal Cancer

In the U.S., approximately 149,000 people will be diagnosed with
cancer of the colon or rectum this year. Half of these patients have
metastatic disease, or cancer that has spread to other organs, at
the time of diagnosis. EGFR is expressed in up to 77.7 % of
colorectal cancer tumors. Colorectal cancer is the third most common
cancer in both men and women.(1)

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. There can be no guarantee that a registrational
submission will me 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, 2005 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.

(1) American Cancer Society: Cancer Facts and Figures 2006.

http://www.cancer.org/downloads/STT/CAFF2006PWSecured.pdf.

Source: Bristol-Myers Squibb Company

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