ERBITUX(R) (Cetuximab) Receives Approval in Japan for Use in Advanced Colorectal Cancer

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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