DUBLIN, IRELAND -- September 17, 2001 -- Antegren® (natalizumab), a humanized monoclonal antibody, demonstrated promising results on multiple endpoints in a Phase II study in multiple sclerosis (MS), according to data presented today at the annual meeting of the European Congress on Treatment and Research in Multiple Sclerosis (ECTRIMS).
Biogen, Inc. and Elan Corporation are collaborating on the development, manufacture and marketing of Antegren, one of the first in a new class of potential therapeutics discovered by Elan. Antegren, an alpha-4 integrin inhibitor, was designed to prevent migration of inflammatory cells from blood vessels into tissues. This pathway was pioneered by both Elan and Biogen.
Elan conducted a Phase II, double-blind, placebo-controlled trial of 213 MS patients at 26 sites in the United States, Canada and the United Kingdom. Patients received either of two Antegren doses (3 mg/kg or 6 mg/kg) or placebo by intravenous infusion every four weeks for six months. Participants in the trial had either relapsing-remitting MS or secondary progressive MS.
The primary analysis was based on magnetic resonance imaging (MRI) scans and showed that patients treated with Antegren for six months had fewer new gadolinium-enhancing lesions than patients treated with placebo. In the placebo group (n=71), the cumulative mean number of new enhancing lesions during the treatment period was 9.6, whereas the Antegren 3 mg/kg group (n=68) had a mean of 0.6 new lesions and the Antegren 6 mg/kg group (n=74) had accumulated 1.2 new lesions during the same period.
"The robust effects of Antegren in reducing MRI activity is promising and suggest that the agent's mechanism of action has potential as a new approach to treating MS. This will be investigated in further trials," said David Miller, M.D., professor of neurology, Institute of Neurology, London, United Kingdom.
Secondary endpoints in the study included the change in the MSFC (MS Functional Composite) and in the EDSS (Expanded Disability Status Score) over the treatment phase. There were no changes seen (in these parameters) in either the placebo or treatment groups over the six months of treatment.
The number of MS relapses over the treatment period -- one of the pre-specified clinical endpoints in the trial -- was also reduced, with 34 relapses in the placebo group compared to 19 in the Antegren 3 mg/kg group and 14 in the Antegren 6 mg/kg group.
"Most neurologists would agree that we need to boost the efficacy of the existing treatments for MS," said George Rice, M.D., professor, clinical neurological sciences, University of Western Ontario, London, Ontario, Canada. "Antegren may provide a new, meaningful treatment option."
Antegren was generally well tolerated. The most common adverse events in the study were headache, asthenia and urinary tract infections. Certain adverse events occurred more commonly with Antegren compared to placebo, such as gastroenteritis, rash, urinary urgency, back pain and fever. Additionally, serious adverse events included infrequent hypersensitivity-like reactions.
Stephen Reingold, Ph.D., Vice President-Research of the National Multiple Sclerosis Society, said, "The impact of Antegren on brain lesions suggests that this agent might have a role in treatment of MS. This is important, since the agent appears to work differently than currently available MS treatments. The outcomes of the planned trials will be eagerly awaited."
More than one million people in North America and Europe have MS, a chronic, often disabling, disease of the central nervous system. Symptoms range from mild, such as numbness in the limbs, to severe, including paralysis or loss of vision. Most people with MS are diagnosed between the ages of 20 and 40 and more women have MS than men.
Elan and Biogen are also studying the potential of Antegren in Crohn's disease, a chronic inflammatory disease of the gastrointestinal tract. Positive data from a Phase II trial in Crohn's disease were presented in May at the annual meeting of the American Gastroenterological Association during Digestive Disease Week. In that trial, a clinical response (decrease of >70 points in the Crohn's disease Activity Index (CDAI)) was achieved in 74 percent of patients in the Antegren 3 mg/kg group (n= 65) versus 38 percent of patients in the placebo group (n=63). Furthermore, remission, defined as a CDAI score of <150 was achieved by 46 percent of patients in the 3mg/kg dose group versus 27 percent in the placebo group.
In the Crohn's disease trial, Antegren was generally well tolerated. Data suggest 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.
Based on the positive Phase II findings in MS and Crohn's disease, the companies intend to move the unique compound into Phase III studies in both indications by the end of this year. The companies are planning to start two Phase III studies in MS, studying Antegren as a monotherapy, as well as in combination with Biogen's Avonex® (Interferon beta-1a).
Antegren is designed to block immune cell adhesion to blood vessel walls and subsequent migration of lymphocytes into tissue. Antegren was discovered in Elan's research facilities in South San Francisco, and both Elan and Biogen have pioneered research into this unique pathway. 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 autoimmune diseases, in addition to MS and Crohn's disease. The companies intend to pursue clinical studies of Antegren in other autoimmune diseases.
SOURCE: Elan Corporation
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Doctor's Guide Publishing Limited
All contents Copyright (c) 1995-2001 Doctor's Guide Publishing Limited