Phase III Study of ERBITUX -TM- -Cetuximab- and High-Dose Radiation in Locally Advanced Head and Neck Cancer Presented at ASCO.

Business Editors/Health/Medical Writers

40th Annual Meeting of American Society of Clinical Oncology 

NEW ORLEANS--(BUSINESS WIRE)--June 5, 2004

ImClone Systems Incorporated (Nasdaq:IMCL), Merck KGaA, Darmstadt, Germany (Frankfurt Stock Exchange:MRK), and Bristol-Myers Squibb Company (NYSE:BMY) today announced the results of an international, randomized phase III study of 424 patients with locally advanced squamous cell carcinoma of the head and neck evaluating the addition of ERBITUX(TM) (Cetuximab) Injection, an IgG1 monoclonal antibody, to high-dose radiation. The study met both its primary endpoint of locoregional control and its secondary endpoint of overall survival. This study was presented today at a press conference during the American Society of Clinical Oncology (ASCO) 40th Annual Meeting.

The percentage of patients who achieved locoregional control at one year and at two years following treatment was 69% and 56% in ERBITUX-treated patients compared to 59% and 48% for those treated with radiation alone. Likewise, the percentage of patients alive at two and three years post-treatment was 62% and 57% for the ERBITUX-treated patients versus 55% and 44% for those treated with radiation alone. Both the duration of locoregional control and the duration of survival were statistically significant (log-rank p-value=0.02 for both endpoints). With a minimum follow-up of 24 months and a median follow-up of 38 months, the median overall survival for the ERBITUX-treated patients was 54 months (95% CI: 36-58+) compared to 28 months (95% CI: 21-38) for patients treated with radiation alone.

The incidence of grade 3/4 mucositis (inflammation of the mucous membrane), a serious adverse event associated with high-dose radiation therapy for head and neck cancer, was similar in both treatment groups (55% in patients receiving radiation plus ERBITUX and 52% in patients who received radiation alone). Three percent of patients in the radiation plus ERBITUX arm and zero percent of patients in the radiation-alone arm experienced grade 3/4 infusion reactions, and grade 3/4 skin reaction occurred in 34 percent of patients receiving radiation plus ERBITUX compared to 18 percent of radiation-alone patients.

The phase III trial (IMCL-9815) examined the impact of combining ERBITUX with high-dose radiation on locoregional disease control and overall survival in 424 patients with advanced squamous cell carcinoma of the oropharynx (area of the throat at the back of the mouth), larynx (voice box) or hypopharynx (cavity at the back of the mouth that opens into the esophagus) that has spread through the head and neck region. Patients were randomized to receive radiation plus weekly ERBITUX therapy (n=211) or radiation alone (n=213) for six to seven weeks.

The companies plan to discuss these findings and other head and neck cancer clinical data with the Food and Drug Administration (FDA), as well as the European Medicines Agency (EMEA).

ERBITUX(TM) (Cetuximab) Approved Indication

ERBITUX is approved by the FDA for use in combination with irinotecan in the treatment of patients with EGFR-expressing, metastatic colorectal cancer who are refractory to irinotecan-based chemotherapy and for use as a single agent in the treatment of patients with EGFR-expressing, metastatic colorectal cancer who are intolerant to irinotecan-based chemotherapy. The effectiveness of ERBITUX for the treatment of colorectal 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.

Outside the U.S., Merck KGaA, Darmstadt, Germany, gained approval for use of ERBITUX in combination with irinotecan in patients with EGFR-expressing metastatic colorectal cancer who have failed prior irinotecan therapy in Switzerland in December 2003, with EU approval expected in June 2004.

In May 2004, Merck KGaA also received approval for ERBITUX in Argentina and Mexico for use in combination with irinotecan or as a single agent in patients with EGFR-expressing metastatic colorectal cancer after failure of irinotecan-including cytotoxic therapy.

ERBITUX Important Safety Information

Severe infusion reactions, rarely fatal and characterized by rapid onset of airway obstruction (bronchospasm, stridor, hoarseness), urticaria, and hypotension, have occurred (3%) with the administration of ERBITUX. Most reactions (90%) are associated with the first infusion of ERBITUX despite the use of prophylactic antihistamines.

Severe cases of interstitial lung disease (ILD), which was fatal in one case, occurred in less than 0.5% of patients receiving ERBITUX.

Dermatologic toxicities, including acneform rash (12% grade 3-4), skin drying and fissuring, and inflammatory or infectious sequelae (e.g. blepharitis, cheilitis, cellulitis, cyst) were reported. Sun exposure may exacerbate these effects.

Other serious adverse events associated with ERBITUX in clinical trials were fever (5%), sepsis (3%), kidney failure (2%), pulmonary embolus (1%), dehydration (5% in patients receiving ERBITUX plus irinotecan, 2% receiving monotherapy) and diarrhea (6% in patients receiving ERBITUX plus irinotecan, 0% with monotherapy).

Additional common adverse events seen in patients receiving ERBITUX plus irinotecan (n=354) or ERBITUX monotherapy (n=279) were acneform rash (88%/90%), asthenia/malaise (73%/49%), diarrhea (72%/28%), nausea (55%/29%), abdominal pain (45%/25%), vomiting (41%/25%), fever (34%/33%) and constipation (30%/28%).

Full prescribing information is available upon request, or at www.ERBITUX.com.

Background Information

ERBITUX binds specifically to epidermal growth factor receptor (EGFR, HER1, c-ErbB-1) on both normal and tumor cells, and competitively inhibits the binding of epidermal growth factor (EGF) and other ligands, such as transforming growth factor-alpha. The EGFR is constitutively expressed in many normal epithelial tissues, including the skin and hair follicle. Over-expression of EGFR is also detected in many human cancers including those of the colon and rectum.

According to the American Cancer Society, approximately 40,000 Americans will be diagnosed with oral, head and neck cancer this year, including cancers of the tongue, mouth, pharynx, and larynx. More than 11,000 will die from the disease in 2004. Approximately 70,000 new cases are diagnosed annually in Europe, with more than 25,000 deaths each year. Treatment for head and neck cancer may include surgery, radiation therapy and chemotherapy or some combination of these.

About ImClone Systems Incorporated

ImClone Systems Incorporated is 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 three programs include growth factor blockers, angiogenesis inhibitors and cancer vaccines. 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. 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, 2003 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.

About Merck KGaA, Darmstadt, Germany

Merck KGaA, Darmstadt, Germany, is a global pharmaceutical and chemical company with sales of EUR 7.2 billion in 2003, a history that began in 1668, and a future shaped by 28,300 employees in 56 countries. Its success is characterized by innovations from entrepreneurial employees. Merck's operating activities come under the umbrella of Merck KGaA, in which the Merck family holds a 74 percent interest and free shareholders own the remaining 26 percent. The former U.S. subsidiary, Merck & Co., has been completely independent of the Merck Group since 1917.

Merck KGaA, Darmstadt, Germany, licensed the right to market ERBITUX outside the U.S. and Canada from ImClone Systems Incorporated of New York in 1998. In Japan, Merck KGaA has co-exclusive marketing rights with ImClone Systems.

Note to editors:

Results of IMC-9815 (Abstract 5507) were presented Saturday, June 5, 8:00 AM CDT during a press conference on aerodigestive cancers sponsored by the American Society of Clinical Oncology (ASCO). Data will be presented to conference attendees Tuesday, June 8, 10:30 AM CDT during an oral presentation session on head and neck cancer.