Elan and Biogen Pioneer New Approach to Treatment of Crohn’s Disease and Multiple Sclerosis

Antegren® (natalizumab), a humanized monoclonal antibody, demonstrated promising results on multiple endpoints in a Phase II study of Crohn’s Disease, a chronic inflammatory disease of the gastrointestinal tract, according to Phase II data presented today at an annual meeting of the American Gastroenterological Association during Digestive Disease Week, the premiere international meeting for the gastroenterology community. Elan Corporation, plc (NYSE: ELN) (“Elan”) and Biogen, Inc. (NASDAQ: BGEN) (“Biogen”) are collaborating on the development, manufacture and marketing of Antegren, one of the first in
a new class of potential therapeutics known as alpha 4 integrin inhibitors that are designed to prevent migration of inflammatory cells from blood vessels to the site of inflammation.

In addition to its potential as a treatment for Crohn’s Disease, Antegren has also been evaluated in a Phase II multiple sclerosis (“MS”) study. The primary endpoint of the study was to show a statistically significant reduction in new gadolinium enhancing MRI brain lesions versus placebo. Elan and Biogen are extremely pleased with the findings from the study. The companies expect to present the Phase II MS data later this year at an appropriate scientific forum. Elan and Biogen met with the Food and Drug Administration (“FDA”) last week to discuss the design of the Phase III studies in MS that are expected to start later this year.

This Phase II study (CD 202) enrolled 244 moderate-severely active patients with Crohn’s Disease (Crohn’s Disease Activity Index (“CDAI”) score 220-450). The randomized, double-blind, placebo-controlled, parallel group study was conducted across eight countries at 38 sites. The patients were randomized to one of four treatment groups: a single 3mg/kg Antegren infusion; two 3mg/kg Antegren infusions at a 4-week interval; two 6mg/kg Antegren infusions at a 4-week interval; or placebo. Patients were followed for 12 weeks following the first infusion and were assessed using the CDAI and changes in quality of life, as assessed by the Inflammatory Bowel Disease Questionnaire (“IBDQ”).

A statistically significant difference in clinical response (decrease of >70 points in CDAI) was noted as early as week two and was maintained through week 12 with a maximal response of 74% in the 3mg/kg dose group versus 38% in the placebo group. Remission, defined as a CDAI score of <150, was achieved by 46% of patients in the 3mg/kg dose group versus 27% in the placebo group. There was also a statistically significant difference in the change from baseline IBDQ score in patients receiving two infusions of Antegren as compared to those receiving placebo at both week 6 and week 12.

In this trial Antegren was generally well tolerated. Data suggests that the most common adverse events reported were headache and abdominal pain. There were no notable differences among treatment groups in the number of patients reporting side effects.

Elan and Biogen met with the FDA last week to discuss the Phase III Crohn’s Disease studies, which are designed to assess both the short-term treatment of active Crohn’s Disease and to assess the long-term durability of responses with Antegren. The companies expect to start Phase III studies in Crohn’s Disease later this year.

“Many existing therapies have problematic side-effects, or have questions concerning safety with long-term use; therefore, other therapies are needed to treat this disease,” said the study’s lead investigator, Paul Rutgeerts, MD, PhD, FRCP, Professor of Medicine and Head of the Department of Endoscopy, Universitaire Ziekenhuizen Leuven, Belgium. “The Phase II data are exciting because they show, for the first time, that this novel humanized monoclonal antibody may provide an effective treatment to induce remission and maintenance of Crohn’s Disease. We look forward to Phase III studies to learn more about this promising new drug.”

Approximately one million people worldwide have Crohn’s Disease, a chronic inflammatory relapsing-remitting disease of the GI tract, which commonly affects both men and women. The onset of disease is in young adults. The disease usually causes diarrhea, crampy abdominal pain, often fever, and at times rectal bleeding. Loss of appetite and subsequent weight loss also may occur. Complications include narrowing of the intestine, obstruction, abscesses, and fistulas (abnormal channels connecting the intestine and other organs, including the skin), malnutrition and decreased growth rate in children. Patients with Crohn’s Disease fluctuate between periods of active disease and remission. The disease can result in frequent hospitalizations—seventy percent of patients will undergo surgery at least once, and thirty percent will need additional operations. A recent study has estimated that the total annual cost of Crohn’s Disease in the United States exceeds $1.7 billion.

“Antegren’s unique therapeutic pathway may be a truly innovative approach for potential treatment of this disease,” said Stephen Hanauer, MD, Professor of Medicine and Clinical Pharmacology, Director, section of Gastroenterology and Nutrition, the University of Chicago Hospitals and Health System. “What is particularly exciting about this study is that results were seen as early as the second week of follow-up.”

“Crohn’s Disease is a serious, chronic disease that can severely impact a patient’s life,” added William J. Sandborn, MD, Professor of Medicine, Mayo Medical School, Head of IBD Research at Mayo Clinic and Co-chair of the Novel Clinical Trials in Inflammatory Bowel Disease session at DDW, where the Antegren Phase II data were presented. “These Phase II data findings are an important contribution to the continuing development of the drug in the treatment and management of this disease.”

Antegren, a humanized monoclonal antibody, is one of the first in a new class of potential therapeutics known as alpha 4 integrin inhibitors that are designed to block immune cell adhesion to blood vessel walls and subsequent migration of lymphocytes into tissue. Antegren binds to the cell surface receptors known as alpha-4-beta 1 (VLA-4) and alpha-4-beta-7. Antegren may be useful in the treatment of a range of inflammatory and non-inflammatory diseases, including Crohn’s Disease and MS.

Antegren was discovered in Elan’s research facilities in South San Francisco, and both Elan and Biogen have pioneered research into this unique pathway. Based on the positive Phase II findings in Crohn’s Disease and MS, the companies intend to move the unique compound into Phase III studies this year.

Elan Corporation, plc is a leading worldwide fully integrated pharmaceutical company headquartered in Ireland, with its principal research, development, manufacturing and marketing facilities located in Ireland, the United States and Israel. Elan is focused on the discovery, development and marketing of therapeutic products and services in neurology, pain management, oncology, infectious disease and dermatology and on the development and commercialization of products using its extensive range of proprietary drug delivery technologies. Elan shares trade on the New York, London and Dublin Stock Exchanges.

Biogen, Inc., winner of the U.S. National Medal of Technology, is a biopharmaceutical company principally engaged in discovering and developing drugs for human healthcare through genetic engineering. Headquartered in Cambridge, MA, the Company’s revenues are generated from international sales of AVONEX? (Interferon beta 1-a) for treatment of relapsing forms of multiple sclerosis, and from the worldwide sales by licenses of a number of products, including alpha interferon and hepatitis B vaccines and diagnostic products ( Prescribing Information ). Biogen’s research and development activities are focused on novel products to treat inflammatory and autoimmune diseases, neurological diseases, cancer, fibrosis and congestive heart failure. The Company maintains active clinical research programs in protein therapeutics, small molecules, genomics and gene therapy. For copies of press releases and additional information about the Company, please consult Biogen’s Homepage on the World Wide Web at

In addition to historical information, this press release contains forward-looking statements within the meaning of the ‘safe harbor’ provisions of the Private Securities Litigation Reform Act of 1995. Reference is made in particular to statements regarding the potential for Antegren as a therapeutic product. These statements are based on the companies’ current beliefs and expectations as to such future outcomes. Drug development involves a high degree of risk. Success in early stage clinical trials does not ensure that later stage or larger scale clinical trials will be successful. Factors which could cause actual results to differ materially from the companies’ current expectations include the risk that the product may not show therapeutic effect or an acceptable safety profile in subsequent trials or may not met applicable regulatory standards, or that problems or delays may arise during clinical trials or in the course of the development, testing or manufacturing of the product as well as the other risks and uncertainties described from time to time in the companies’ periodic reports filed with the Securities and Exchange Commission.

Editor’s note: The Phase II Crohn’s Disease data (abstract #682) were presented an annual meeting of the American Gastroenterological Association, “Novel Clinical Trials in IBD,” during Digestive Disease Week on Wednesday, May 23, at 11:45 am.