Elan
Corporation, plc (NYSE: ELN) (“Elan”) and Biogen, Inc. (Nasdaq: BGEN)
(“Biogen”) announced today that they have enrolled and dosed the first
patients in their multi-center Phase III clinical trials of Antegren(R)
(natalizumab) in multiple sclerosis (“MS”). Elan and Biogen expect to enroll
and dose the first patients in their Phase III clinical trials for Crohn’s
disease before year-end.
Biogen and Elan are collaborating on two trials in MS. The AFFIRM
(Antegren safety and efficacy in relapsing-remitting MS) trial is a two year,
randomized, multi-center, placebo-controlled, double blind study of
approximately 900 patients, designed to determine whether Antegren is
effective in slowing the rate of disability in MS and reducing the rate of
clinical relapses. The second trial, known as SENTINEL (safety and efficacy
of natalizumab in combination with Avonex(R) (Interferon beta-1a) in subjects
with relapsing-remitting MS), is a two year, randomized, multi-center,
placebo-controlled, double blind study of approximately 1,200 patients. The
SENTINEL trial, which will be one of the largest conducted in MS, is designed
to determine whether the treatment of MS with Antegren in combination with
Avonex is more effective than Avonex treatment alone in slowing the rate of
disability in MS and in reducing the rate of clinical relapses.
Elan and Biogen are also conducting two Phase III clinical trials in
Crohn’s disease. The first Phase III trial, the largest to be conducted in
Crohn’s disease, is a randomized, multi-center, placebo-controlled, double
blind study of approximately 850 patients, which is designed to measure both
the response and the ability to induce remission in patients at week 10 of
administration of Antegren. The second randomized, multi-center, placebo
controlled, double blind Phase III trial of approximately 300 patients is
designed to evaluate the effect of Antegren on the duration of response and
remission in patients with Crohn’s disease.
Compelling Data Seen in Phase II MS Trial
In September 2001, Biogen and Elan presented promising data from the Phase
II trial of Antegren in MS at the annual meeting of the European Congress on
Treatment and Research in Multiple Sclerosis. This was a double blind,
placebo-controlled trial of 213 patients who had relapsing forms of MS.
The primary analysis was based on magnetic resonance imaging (“MRI”) scans
and showed that patients treated with Antegren for 6 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, while 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.
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.
Promising Crohn’s Disease Data Seen in Phase II Trial
Elan and Biogen presented positive data from a Phase II trial in Crohn’s
disease 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% of patients in the Antegren 3 mg/kg group (n=65) versus 38% of
patients in the placebo group (n=63). Remission, defined as a CDAI score of
less than or equal to 150, was achieved by 46% of patients in the Antegren
3 mg/kg dose group versus 27% in the placebo group.
Tolerability
Antegren was generally well tolerated by patients in both the MS and
Crohn’s disease studies. The most common adverse events were headache,
asthenia and urinary tract infections (in patients with MS) and headache and
abdominal pain (in patients with Crohn’s disease). 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.
Mechanism of Action
Antegren, the first of a revolutionary new class of compounds known as
selective adhesion molecule inhibitors, is designed to selectively 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 integrins, which
are believed to play an important role in the trafficking of mononuclear
cells, such as lymphocytes, into sites of inflammation. 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.
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(R) for treatment of relapsing forms of multiple sclerosis, and from
the worldwide sales by licensees of a number of products, including alpha
interferon and hepatitis B vaccines and diagnostic products. More than
100,000 patients throughout the world take Biogen’s drug, Avonex(R), the
world’s leading therapy for relapsing forms of multiple sclerosis. (Please
see full prescribing information at http://www.avonex.com.) 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
http://www.biogen.com.
Elan Corporation, plc is a leading worldwide, fully integrated
biopharmaceutical company headquartered in Ireland, with its principal
research, development, manufacturing and marketing facilities located in
Ireland, the United States and the United Kingdom. Elan is focused on the
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. For copies of press releases and additional information
about the company, please consult Elan’s homepage on the worldwide web at
http://www.elan.com.
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 and the Companies’ future development plans. 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 expectation include the risk
that the product may not show therapeutic effect or an acceptable safety
profile in subsequent trials or may not meet 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.