Biogen Idec

Biogen Idec
Elan Corporation

Elan Corporation

April 12, 2005 16:15 ET

TYSABRI Two-Year Monotherapy Data Support Positive One-Year Efficacy Findings and Show Significant Reduction in Risk of Disability Progression


NEWS RELEASE TRANSMITTED BY CCNMatthews

FOR: BIOGEN IDEC

NASDAQ SYMBOL: BIIB

AND ELAN CORPORATION

NYSE SYMBOL: ELN

APRIL 12, 2005 - 16:15 ET

TYSABRI Two-Year Monotherapy Data Support Positive
One-Year Efficacy Findings and Show Significant
Reduction in Risk of Disability Progression

CAMBRIDGE, Mass. and DUBLIN, Ireland--(CCNMatthews - Apr 12, 2005) -

Data Presented at American Academy of Neurology Meeting

Two-year data from the AFFIRM Phase III monotherapy trial presented
today for the first time, showed that treatment with TYSBARI®
(natalizumab) led to a significant reduction in disability progression,
the rate of clinical relapses and brain lesions in patients with
relapsing forms of multiple sclerosis (MS). These data were presented at
the 57th annual American Academy of Neurology (AAN) meeting in Miami
Beach, FL.

AFFIRM met all primary and secondary endpoints, including disability
progression and relapse rate. TYSABRI treatment was also associated with
a low level of immunogenicity.

TYSABRI treatment led to a 42 percent (p equals 0.0002) reduction in the
risk of disability progression compared to placebo. TYSABRI also reduced
the rate of clinical relapses by 67 percent (p<0.0001) compared to
placebo, which was sustained and consistent with the previously reported
one-year results.

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.

"While an evaluation is underway to better understand recent
developments with TYSABRI, these data confirm the efficacy of TYSABRI on
clinical relapse and define its impact on disability progression," said
Chris Polman, MD, PhD, lead investigator of the AFFIRM study, professor
of Neurology at Free University Medical Centre, and clinical and
scientific director of the Multiple Sclerosis Centre at the VU Medical
Centre, Amsterdam. "Disability progression is an important consideration
in managing MS. The efficacy of TYSABRI underscores its importance for
MS patients."

Results From Two-Year AFFIRM

AFFIRM is a two-year, randomized, multi-center, placebo-controlled,
double-blind study of 942 patients conducted in 99 sites worldwide,
evaluating the effect of TYSABRI on the progression of disability as
measured by at least a one-point increase on the Expanded Disability
Status Scale (EDSS) sustained for three months, and the rate of clinical
relapses. Progression of disability is a sustained change that has a
long-term impact on a patient's functional and ambulatory performance.
Patients in AFFIRM were randomized to receive either a 300 mg IV
infusion dose of TYSABRI (n equals 627) or placebo (n equals 315) every
four weeks.

Disability

TYSABRI-treated patients were less likely to experience progression of
disability. The risk of disability progression sustained for three
months was reduced by 42 percent relative to placebo (p equals 0.0002),
the two-year primary endpoint. Additionally, after two years, 29 percent
of placebo-treated patients had progressed, while only 17 percent of
TYSABRI-treated patients progressed, representing a 41 percent reduction
in the proportion of patients progressing (p<0.0001).

TYSABRI also slowed the progression of disability as demonstrated by the
mean Multiple Sclerosis Functional Composite (MSFC) score. The MSFC
consists of three tests that evaluate ambulation, upper extremity
dexterity and cognitive function.

A pre-defined sensitivity analysis of the primary endpoint defined
progression as at least a one-point increase on the EDSS sustained for
six months. Using this definition, the risk of disability progression
was reduced by 54 percent with TYSABRI treatment.

Relapse Rate

Data also demonstrated a 67 percent reduction in the rate of clinical
relapses relative to placebo (p<0.0001) over two years, which was
sustained and consistent with the previously reported one-year results.
The annualized relapse rate was 0.22 for TYSABRI-treated patients
compared to 0.67 for placebo-treated patients. The proportion of
patients who remained relapse free was 67 percent in the TYSABRI-treated
group compared to 41 percent in the placebo-treated group (p<0.0001).

MRI measures

MRI analysis examining different types of brain lesions is used in the
initial diagnosis of MS and is a marker of ongoing and previous disease
activity and damage. TYSABRI treatment resulted in sustained and
statistically significant reductions in the number and volume of
gadolinium enhancing, T2-hyperintense and T1-hypointense lesions
compared to placebo. The pre-specified secondary endpoint MRI measures
were the volume of T2-hyperintense lesions and the number of new
T1-hypointense lesions.

Over two years, there was a significant difference in the burden of
disease as measured by change in T2-hyperintense lesion volume.
Placebo-treated patients experienced an increase in burden of disease
while TYSABRI-treated patients had a decrease. In addition, TYSABRI
demonstrated a 76 percent reduction in the mean number of new
T1-hypointense lesions compared to placebo.

AFFIRM Safety Summary

The two-year adverse event profile in AFFIRM was consistent with
previously reported one-year results. Common events included headache,
fatigue, urinary tract infection, depression, lower respiratory tract
infection, limb and joint pain, and pharyngitis. The rate and incidence
of infections in TYSABRI-treated and placebo-treated patients were
similar. Serious infections occurred in 3.2 percent and 2.6 percent of
TYSABRI-treated and placebo-treated patients, respectively. TYSABRI has
also been associated with hypersensitivity reactions, including serious
systemic reactions that occurred at an incidence of less than 1 percent
of patients.

Immunogenicity

All biologics have the potential to induce antibody formation. Analysis
of the two-year data from the AFFIRM study indicated a low level of
immunogenicity associated with TYSABRI. Patients were tested for
antibodies every 12 weeks. Antibodies were detected in approximately 9
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.

"We believe in the significant therapeutic benefit of TYSABRI in MS, a
disease with high unmet need," said Burt Adelman, MD, executive vice
president, Development, Biogen Idec. "Biogen Idec and Elan are working
diligently to evaluate extensive data from our clinical trials,
consulting with leading experts and with regulatory agencies throughout
this process. We hope to define a path forward for this product, and our
future steps, as always, will be guided by our commitment to people
living with MS."

"We are very encouraged by the two-year results which support the
efficacy of TYSABRI in MS," said Lars Ekman, MD, PhD, executive vice
president and president, Research and Development, Elan. "Patient safety
is our top priority, and we are working closely with the regulatory
agencies to define the appropriate benefit-risk profile for TYSABRI as a
new option to treat MS."

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.

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Contact Information

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