NEW YORK, June 11 /PRNewswire-FirstCall/ -- ImClone Systems
Incorporated (Nasdaq: IMCL) and Bristol-Myers Squibb Company (NYSE: BMY)
today announced that the U.S. Food and Drug Administration (FDA) has
accepted, for filing and review, a supplemental biologics license
application (sBLA) for ERBITUX(R) (Cetuximab). With this application, the
companies seek to include evidence of improved overall survival in the
product labeling for ERBITUX in the third- line treatment of patients with
metastatic colorectal cancer (mCRC). The Companies also announced that the
ERBITUX sBLA has been granted a priority review. Based on the priority
review, the likely FDA action date for the sBLA is early October. If the
sBLA is approved, ERBITUX would be the only biologic therapy to demonstrate
overall survival as a single agent in patients with metastatic colorectal
cancer.
The sBLA, which is based on results from a large, randomized,
multicenter, Phase III trial, seeks to update the monotherapy indication to
include patients with EGFR-expressing mCRC whose disease has progressed
following, or who were not candidates to receive, irinotecan- or
oxaliplatin-based chemotherapy. The sBLA also seeks to include data on
overall survival relative to best supportive care - considered to be all
approved palliative therapies designed to alleviate pain and treat other
effects caused by advanced colorectal cancer in this patient population.
Currently, in mCRC, ERBITUX is indicated as a monotherapy for
EGFR-expressing mCRC patients who are intolerant to irinotecan-based
therapy. ERBITUX is also approved in combination for the treatment of
EGFR-expressing, mCRC in combination with irinotecan for patients who are
refractory to irinotecan-based chemotherapy; this combination indication
would remain unchanged. These indications were approved based on objective
response rates.
About Colorectal Cancer
In the U.S., approximately 154,000 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.
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' 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 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 the sBLA submission described above will receive FDA
approval, that if the sBLA is approved, the product labeling will be the
product labeling described in this press release, or 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, in our Quarterly Reports
on Form 10-Q and our Current Reports on Form 8- K.. 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
 back to top
Related links:
http://www.ERBITUX.com/
CONTACT:
Rebecca Gregory, Corporate Communications of
ImClone Systems Incorporated, +1-646-638-5058, media@imclone.com,
Media, Madeline Malia, +1-609-252-3347, Madeline.Malia@bms.com,
Tony Plohoros, +1-609-252-7938, Tony.Plohoros@bms.com, Investors,
John Elicker, +1-212-546-3775, John.Elicker@bms.com, all of
Bristol-Myers Squibb
|
