Biogen Idec

Biogen Idec
Elan

Elan

April 13, 2005 15:45 ET

Positive One-Year Data From SENTINEL Trial Evaluating Addition of TYSABRI to AVONEX Presented at American Academy of Neurology Meeting


NEWS RELEASE TRANSMITTED BY CCNMatthews

FOR: BIOGEN IDEC

NASDAQ SYMBOL: BIIB

AND ELAN

NYSE SYMBOL: ELN

APRIL 13, 2005 - 15:45 ET

Positive One-Year Data From SENTINEL Trial Evaluating
Addition of TYSABRI to AVONEX Presented at American
Academy of Neurology Meeting

CAMBRIDGE, Mass. and DUBLIN, Ireland--(CCNMatthews - Apr 13, 2005) -



Data from GLANCE Safety Study Also Presented

One-year data from the Phase III SENTINEL trial, presented at the 57th
annual American Academy of Neurology (AAN) meeting in Miami Beach, FL,
demonstrated that when TYSABRI® (natalizumab) was added to AVONEX®
(Interferon beta-1a) in patients with relapsing forms of multiple
sclerosis (MS), the annualized clinical relapse rate was reduced by 54
percent over the effect of AVONEX alone (p<0.001). In addition, these
data, presented for the first time at a major medical meeting,
demonstrated that the addition of TYSABRI to AVONEX resulted in
significantly fewer new or newly enlarging T2-hyperintense lesions and
gadolinium-enhancing lesions than AVONEX alone, and that the proportion
of TYSABRI/AVONEX patients who remained relapse-free was significantly
higher than in the AVONEX group.

On February 28, 2005, Biogen Idec and Elan Corporation, plc announced
that they voluntarily suspended TYSABRI from the U.S. market and all
ongoing clinical trials. This decision was based on reports of
progressive multifocal leukoencephalopathy (PML), a rare and frequently
fatal, demyelinating disease of the central nervous system. Biogen Idec
and Elan's comprehensive safety evaluation concerning TYSABRI and any
possible link to PML is ongoing. The results of this safety evaluation
will be discussed with regulatory agencies to determine possible
re-initiation of dosing in clinical trials and future commercial
availability.

"SENTINEL is a large, well-designed clinical trial that for the first
time evaluated the efficacy of add-on therapy for MS patients who
continued to experience disease activity despite interferon therapy,"
said Richard Rudick, MD, lead investigator of the SENTINEL trial and
director of the Mellen Center for MS Treatment and Research at Cleveland
Clinic Foundation. "We look forward to learning more from the ongoing
evaluation of TYSABRI."

SENTINEL One-Year Results

SENTINEL is a two-year, randomized, multi-center, placebo-controlled,
double-blind study of 1,171 AVONEX-treated patients in 123 clinical
trial sites worldwide. AVONEX-treated patients who continued to
experience disease activity were randomized to add TYSABRI (n equals
589) or placebo (n equals 582) to their standard regimen.

The primary endpoint at one-year was the reduction in the rate of
clinical relapses. The addition of TYSABRI to AVONEX resulted in a 54
percent reduction in the rate of clinical relapses over the effect of
AVONEX alone (p<0.001). The annualized relapse rate was 0.36 for
patients receiving TYSABRI when added to AVONEX versus 0.78 with AVONEX
plus placebo.

Analysis of annualized relapse rate by pre-specified subgroups of
disease severity, including baseline Expanded Disability Status Scale
(EDSS) (measured on a scale 0-10) or relapse history, supported the
primary endpoint finding. In patients with an EDSS greater than or equal
to 4.0, TYSABRI reduced the relapse rate by 51 percent, while in
patients with an EDSS less than 4.0, it reduced the relapse rate by 53
percent. Additionally, in patients with more than two relapses in the
year prior to study entry, TYSABRI reduced the annualized relapse rate
by 55 percent, while in patients with one relapse, TYSABRI reduced the
annualized relapse rate by 53 percent.

SENTINEL also met all secondary endpoints, including MRI measures. In
the group treated with TYSABRI plus AVONEX, 67 percent of patients
developed no new or newly enlarging T2-hyperintense lesions compared to
40 percent in the AVONEX plus placebo group (p<0.001). On the one-year
MRI scan, 96 percent of TYSABRI plus AVONEX-treated patients had no
gadolinium-enhancing lesions compared to 76 percent of AVONEX plus
placebo-treated patients (p<0.001). The proportion of patients who
remained relapse-free was 67 percent in the TYSABRI plus AVONEX-treated
group compared to 46 percent in the AVONEX plus placebo-treated group
(p<0.001).

TYSABRI One-Year Safety

The adverse event profile in SENTINEL and AFFIRM were similar at one
year. Common adverse events included headache, fatigue, urinary tract
infection, depression, lower respiratory tract infection, joint pain and
abdominal discomfort. The rate of infection was approximately one per
patient-year in both TYSABRI-treated patients and placebo-treated
patients. Serious infections occurred in 1.3 percent of placebo treated
patients and 2.1 percent of TYSABRI-treated patients. TYSABRI has been
associated with hypersensitivity reactions, including serious systemic
reactions, which occurred at an incidence of less than 1 percent of
patients.

The two PML cases reported in MS were in patients treated with more than
two years of AVONEX plus TYSABRI.

TYSABRI Immunogenicity

All biologics have the potential to induce antibody formation. Analysis
of the one-year results indicated a low level of immunogenicity
associated with TYSABRI. Patients were tested for antibodies every 12
weeks in the AFFIRM and SENTINEL trials. Antibodies were detected in
approximately 10 percent of patients at least once during treatment,
with 6 percent of patients remaining persistently positive. Persistently
positive antibodies were associated with a substantial decrease in
efficacy and an increase in certain infusion-related adverse events.
Almost all patients who tested positive for antibodies did so within the
first 12 weeks of treatment.

"The one-year results from SENTINEL add to the compelling data set for
TYSABRI. At the conclusion of our extensive safety evaluation, we hope
to have a clearer understanding of the product's efficacy and safety
profile and the prudent next steps," said Burt Adelman, MD, executive
vice president, Development, Biogen Idec.

"Patient safety remains our first priority in all matters and these data
will be considered within the context of our ongoing safety evaluation
to determine the most appropriate future course," said Lars Ekman, MD,
PhD, executive vice president and president, Research and Development,
Elan.

GLANCE Results

Results from GLANCE, a Phase II study evaluating the safety and
pharmacokinetics of TYSABRI when added to Copaxone® (glatiramer
acetate), were also presented today at the AAN meeting. GLANCE is a
24-week study that enrolled 110 MS patients who were relapsing on
Copaxone. When TYSABRI was added to Copaxone, there was no increase in
the rate of new active MRI lesion formation, a safety measure and the
primary endpoint of the study. Because of the short duration of this
study, further study would be necessary to evaluate the safety and
efficacy of TYSABRI when added to Copaxone.

About TYSABRI

Biogen Idec and Elan are collaborating equally on the development of
TYSABRI in MS, Crohn's disease, and rheumatoid arthritis. On February
28, 2005, Biogen Idec and Elan announced that they voluntarily suspended
TYSABRI from the U.S. market and all ongoing clinical trials. Worldwide
regulatory agencies are being kept informed of developments related to
TYSABRI.

Information about TYSABRI, including the voluntary suspension of
marketing, U.S. prescribing information and support services, is
available through a single toll-free number (1-800-456-2255), and via
www.TYSABRI.com.

About Multiple Sclerosis

MS is a chronic disease of the central nervous system that affects
approximately 400,000 people in North America and more than one million
people worldwide. It is a disease that affects more women than men, with
onset typically occurring between 20 and 40 years of age. Symptoms of MS
may include vision problems, loss of balance, numbness, difficulty
walking and paralysis.

About Biogen Idec

Biogen Idec (NASDAQ: BIIB) creates new standards of care in oncology and
immunology. As a global leader in the development, manufacturing, and
commercialization of novel therapies, Biogen Idec transforms scientific
discoveries into advances in human healthcare. For product labeling,
press releases and additional information about the company, please
visit http://www.biogenidec.com.

About Elan

Elan Corporation (NYSE: ELN), plc is a neuroscience-based biotechnology
company. We are committed to making a difference in the lives of
patients and their families by dedicating ourselves to bringing
innovations in science to fill significant unmet medical needs that
continue to exist around the world. Elan shares trade on the New York,
London and Dublin Stock Exchanges. For additional information about the
company, please visit http://www.elan.com.

Safe Harbor/Forward Looking Statements

This press release contains forward-looking statements regarding the
potential for TYSABRI. These statements are based on the companies'
current beliefs and expectations, and are subject to risks and
uncertainties that could cause actual results to differ materially.
There is no assurance, for example, that the serious adverse events
discussed above were not caused by TYSABRI, that there are not or will
not be more such serious adverse events or that we will be able to gain
sufficient information to fully understand the risks associated with the
product. There is also no assurance that the companies will be able to
resume marketing and sales of TYSABRI. For more detailed information on
the risks and uncertainties associated with TYSABRI and the companies'
drug development and other activities, see the periodic and other
reports of Biogen Idec Inc. and Elan Corporation, plc filed with the
Securities and Exchange Commission. The companies assume no obligation
to update any forward-looking statements, whether as a result of new
information, future events or otherwise.

-30-

Contact Information

  • FOR FURTHER INFORMATION PLEASE CONTACT:
    Media Contacts:
    Biogen Idec
    Amy Brockelman, 617-914-6524
    or
    Elan
    Anita Kawatra/Brian McGlynn, 212-407-5740 or 800-252-3526
    Investor Contacts:
    Biogen Idec
    Elizabeth Woo, 617-679-2812
    or
    Elan
    Emer Reynolds, 353 1 709 4000 or 800-252-3526