Data Presented at the American Academy of Neurology's Annual Meeting Provide Update on Utilization and Safety of TYSABRI(R) in Patients with Multiple Sclerosis

03 May 2007

Additional Data From Extension Study Presented Show TYSABRI Benefit is Sustained Over Three Years

BOSTON--(BUSINESS WIRE)--Biogen Idec (NASDAQ: BIIB - News) and Elan Corporation, plc (NYSE: ELN - News) announced today that new data from the TOUCH Prescribing Program(TM) and TYGRIS safety study confirm the safety profile from previous clinical studies of TYSABRI® (natalizumab). Also presented at the 59th annual meeting of the American Academy of Neurology in Boston, MA were extension study data that showed that TYSABRI has a sustained treatment effect on clinical relapses and the risk of disability progression in multiple sclerosis (MS) patients treated for up to three years. The companies recently reported that as of mid-April 2007 approximately 12,500 patients have been prescribed TYSABRI worldwide. The companies estimate that in both commercial use and clinical trials, there are currently over 10,000 patients on TYSABRI therapy worldwide.

"The findings from the safety update combined with the data showing the sustained effect of TYSABRI in patients treated for up to three years, contribute to our evolving understanding of the utilization of this therapy as an important treatment option for people living with the debilitating effects of MS," said Paul O'Connor, MD, St. Michael's Hospital, Toronto, Ontario, Canada, lead investigator of the TYSABRI extension study.

TYSABRI Update

TYSABRI is available in the US through the TOUCH Prescribing Program. All prescribers, infusion sites and patients receiving TYSABRI are required to enroll in TOUCH. Safety information is also collected through ongoing clinical trials and registries, including STRATA, TYGRIS and the pregnancy registry. According to data available to the companies as of April 23, 2007, there have been no new reports of confirmed cases of progressive multifocal leukoencephalopathy (PML) or other serious opportunistic infections (OIs). The data confirm the safety profile from previous clinical studies of TYSABRI and will continue to expand the knowledge of the long-term safety and tolerability of TYSABRI.

The combination of TOUCH, TYGRIS and the pregnancy registry will be the largest long-term follow-up undertaken for an MS therapy, and the companies plan to continue to provide similar updates at upcoming medical meetings.

The companies recently announced that as of mid-April, approximately 12,500 patients have been prescribed TYSABRI worldwide. In both commercial use and clinical trials, there are currently over 10,000 patients on TYSABRI therapy worldwide.

TYSABRI Efficacy Sustained through Three Years

Patients who participated in the Phase III TYSABRI program were eligible to enroll in an open-label extension study that evaluated the therapy's long-term effects. Included in this were patients from AFFIRM, a randomized, double-blind, placebo-controlled, two-year monotherapy study of TYSABRI that enrolled 942 patients (627 patients on TYSABRI, 315 on placebo). In AFFIRM, TYSABRI reduced the annualized relapse rate in patients with MS by 67% (p<0.001) and the risk of 12-week sustained disability progression by 42% (p<0.001) compared with placebo.

In the intent to treat analysis, the annualized relapse rate for patients treated with TYSABRI over the three-year period was 0.23, translating into an average of one relapse every 4.3 years. The relapse rate also continued to remain low over the three-year treatment period with TYSABRI: 0.27 during the first year; 0.20 during the second year; and 0.15 during the third year (based on 531 patients who entered the extension study, which includes approximately 250 patients with nearly three years of continuous therapy).

In addition, TYSABRI also decreased the cumulative probability of disability progression sustained for six months compared to placebo. The estimated proportion of patients who had 24-week sustained disability progression at two years was 11% in patients treated with TYSABRI compared to 23% in patients treated with placebo, a 54% relative reduction.

This effect was maintained in patients treated with TYSABRI for up to three years with 13% showing 24-week sustained disability progression.

About TOUCH and TYGRIS

Before initiating treatment, all US patients, prescribers and infusion sites must be enrolled in the TOUCH Prescribing Program (TYSABRI Outreach: Unified Commitment to Health). TOUCH is designed to determine the incidence of and risk factors for serious OIs, including PML, and to monitor patients for signs and symptoms of PML while promoting informed benefit/risk discussions prior to initiating TYSABRI treatment. Physicians report on PML, serious OIs, deaths and discontinuation of therapy on an ongoing basis.

TYGRIS (TYSABRI Global ObseRvation Program In Safety) is expected enroll 5,000 patients worldwide, including approximately 3,000 patients from TOUCH. Patients in TYGRIS are evaluated at baseline and every six months thereafter for five years. Researchers will evaluate data including medical/MS history; prior TYSABRI use; prior use of immunomodulatory, antineoplastic, or immunosuppressive agents; and all serious adverse events, including PML and other serious OIs, and malignancies.

The information provided here is derived from voluntary adverse event reporting. It is possible that not all reactions have been reported, or that some reactions are not reported to Biogen Idec or Elan in a timely manner.

About TYSABRI

In the US, TYSABRI is approved as a monotherapy treatment for relapsing forms of MS. TYSABRI increases the risk of PML, an opportunistic viral infection of the brain that usually leads to death or severe disability. Patients should be monitored at regular intervals for any new or worsening signs or symptoms suggestive of PML Because of the increased risk of PML, TYSABRI is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, alternate MS therapies. It is available in the US only through a restricted distribution program called the TOUCH Prescribing Program. According to product labeling, after two years, TYSABRI treatment led to a 67% relative reduction (p<0.001) in the annualized relapse rate compared to placebo and reduced the relative risk of disability progression by 42% (p<0.001). TYSABRI treatment also resulted in sustained and statistically significant reductions in brain lesion activity as measured by MRI. Changes in MRI findings often do not correlate with changes in the clinical status of patients (e.g., disability progression). The prognostic significance of the MRI findings in these studies has not been evaluated.

In the European Union, TYSABRI is indicated as a single disease-modifying therapy in highly active elapsing-remitting MS patients. Because of the increased risk of PML, it is for patients with high disease activity despite treatment with a beta-interferon or in patients with rapidly evolving severe relapsing-remitting MS.

According to product labeling in the EU, after two years, TYSABRI treatment led to a 68% relative reduction (p<0.001) in the annualized relapse rate compared to placebo and reduced the relative risk of disability progression by 42-54% (p<0.001).

Serious adverse events that occurred in TYSABRI-treated patients included hypersensitivity reactions (e.g., anaphylaxis), infections, depression and gallstones. In MS trials, the incidence and rate of other serious and common adverse events, including the overall incidence and rate of infections, were balanced between treatment groups. Herpes infections were slightly more common in patients treated with TYSABRI. Serious opportunistic and other atypical infections have been observed in TYSABRI-treated patients, some of whom were receiving concurrent immunosuppressants. Common adverse events reported in TYSABRI-treated patients include headache, fatigue, infusion reactions, urinary tract infections, joint and limb pain, lower respiratory infections, rash, gastroenteritis, abdominal discomfort, vaginitis, and diarrhea.

Natalizumab reduces vision loss in patients with Relapsing Multiple Sclerosis

From the Departments of Neurology and Ophthalmology (L.J.B., S.L.G.), University of Pennsylvania School of Medicine, Philadelphia, PA; Department of Neurology (P.A.C.), The Johns Hopkins University School of Medicine, Baltimore, MD; Hôpital Neurologique (C.C.), Lyon, France; Institute of Neurology (G.G.), London, UK; General Teaching Hospital (E.H.), Prague, Czech Republic; St. Vincent's University Hospital (M.H.), Dublin, Ireland; University Hospital Basel (L.K., E.W.R.), Basel, Switzerland; Mt. Sinai School of Medicine (F.D.L.), New York, NY; St. Michael's Hospital (P.W.O.), Toronto, Ontario, Canada; Multiple Sclerosis Center at Texas Neurology (J.T.P.), Dallas, TX; Vrije Universiteit Medical Center (C.H.P.), Amsterdam, the Netherlands; Mellen Center for Multiple Sclerosis Research (R.A.R), Cleveland Clinic Foundation, Cleveland, OH; MS Center of Atlanta (W.H.S.), Atlanta, GA; Silesian Medical University (A.W.), Katowice, Poland; Baird Multiple Sclerosis Center (B.W.G.), State University of New York at Buffalo, Buffalo, NY; Consultants in Neurology (D.R.W.), Multiple Sclerosis Center, Northbrook, IL; Biogen Idec (F.L., M.A.P.), Cambridge, MA.

Objective: To examine the effects of natalizumab on low-contrast letter acuity as a prespecified tertiary endpoint in two randomized clinical trials and to evaluate the usefulness of low-contrast letter acuity testing as a candidate test of visual function in multiple sclerosis (MS).

Methods: AFFIRM and SENTINEL were randomized, double-blind, placebo-controlled, multicenter, phase 3 clinical trials of natalizumab in relapsing MS. Natalizumab was evaluated as monotherapy in AFFIRM and as add-on to interferon beta-1a in SENTINEL. Vision testing was performed at 100% contrast (visual acuity) and low-contrast (2.5% and 1.25%).

Results: The risk of clinically significant visual loss (predefined as a two-line worsening of acuity sustained over 12 weeks) at the lowest contrast level (1.25%) was reduced in the natalizumab treatment arms by 35% in AFFIRM (hazard ratio = 0.65; 95% CI: 0.47 to 0.90; p = 0.008) and by 28% in SENTINEL (hazard ratio = 0.72; 95% CI: 0.54 to 0.98; p = 0.038, Cox proportional hazards models). Mean changes in vision scores from baseline were also significantly different, reflecting worsening in non-natalizumab groups.

Conclusions: Natalizumab reduces visual loss in patients with relapsing multiple sclerosis. Low-contrast acuity testing has the capacity to demonstrate treatment effects and is a strong candidate for assessment of visual outcomes in future multiple sclerosis trials.

New Pharmacoeconomic Data on TYSABRI® Demonstrate Significant Reduction in Steroid Use and Hospitalizations in Patients with Multiple Sclerosis

6 October 2006

CAMBRIDGE, Mass. & DUBLIN, Ireland--(BUSINESS WIRE)--Oct. 6, 2006--Biogen Idec (NASDAQ: BIIB) and Elan Corporation, plc (NYSE: ELN) announced that data to be presented today at the Academy of Managed Care Pharmacy's (AMCP) 2006 Educational Conference in Chicago, IL show that in Phase III studies TYSABRI® (natalizumab) therapy significantly reduced corticosteroid use and hospitalizations, and increased the proportion of MS patients with no disease activity. Findings will also be presented that demonstrate the positive impact of TYSABRI on a number of health-related quality of life of measures (QoL) and the cost-effectiveness of MS therapies.

Data Demonstrate TYSABRI Reduced Corticosteroid Use, Hospitalizations and Increases the Proportion of Disease-Free Patients

Data presented today from the AFFIRM monotherapy study (two-year, randomized, multi-center, placebo-controlled, double-blind study of 942 patients conducted in 99 sites worldwide), showed the impact of TYSABRI on two pre-specified endpoints, the annualized rate of relapses requiring corticosteroid use and the annualized rate of hospitalizations due to MS. Data showed there was a 69% relative reduction in the annualized rate of relapses requiring steroids for patients treated with TYSABRI compared to those treated with placebo (0.133 in the TYSABRI group vs. 0.432 in the placebo group(p<0.001)). The study also showed that TYSABRI therapy resulted in a 65% relative reduction in the annualized rate of MS-related hospitalizations over two years (0.034 in the TYSABRI group vs. 0.097 in the placebo group(p<0.001)).

A post-hoc analysis was also conducted to determine the proportion of patients free of disease activity over two years. To determine this, a retrospective analysis was conducted to evaluate both clinical and magnetic resonance imaging (MRI) measures. Patients with no disease activity were defined as patients who experienced no additional relapses or progression of physical disability and exhibited stable MRI measures without any new gadolinium-enhancing, T2-hyperintense, or T1-hypointense lesions. Data presented today suggest that TYSABRI significantly increased the proportion of disease-free patients by 79% over two years compared with placebo (28% vs. 6%, respectively; p<0.001).

Cost Effectiveness of MS Therapies

A model was constructed by Xcenda, formerly Applied Health Outcomes, to compare the cost per relapse avoided among the five approved disease-modifying MS therapies to treat relapsing forms of MS. Overall cost of therapy was calculated using the US wholesale acquisition drug cost, and costs associated with drug administration, patient monitoring and treatment of relapses. The costs associated with adverse events were not assessed as part of this model. Effectiveness was defined as the number of relapses avoided with treatment, which was calculated as the number of relapses for a non-treated population multiplied by published relapse rate reductions for the therapies.(1) Based on the model developed, the cost per relapse per year avoided was lowest for TYSABRI. The cost per relapse avoided for TYSABRI was between $12,730 and $23,274 lower than that of the other approved disease-modifying therapies.

Data Show TYSABRI Had Improvement in Quality of Life Assessments

Quality of Life (QoL) was assessed using three different measures, the Multiple Sclerosis Quality of Life Inventory (MSQLI), the Short Form-36 Health Survey (SF-36), which is a component of the MSQLI, and a Visual Analogue Scale (VAS). The MSQLI is an MS-specific battery of 10 scales that measure disease impact on QoL, including fatigue, pain, sexual function, bowel and bladder function, visual impairment, mental health and need for social support. The SF-36 is comprised of 36 questions designed to assess patients' physical and mental well-being. General well-being was also measured using the VAS.

In data presented today from the AFFIRM study, patients in the TYSABRI-treated group realized a significant improvement in physical measures of the SF-36 compared with a decline in the placebo-treated group (p=0.003). A significant improvement was also seen in the mental component of the SF-36 in patients treated with TYSABRI compared with a decline in the placebo-group (p=0.011). Significant benefits were also seen using the VAS (p=0.007).

About TYSABRI

In the US, TYSABRI is approved as a monotherapy treatment for relapsing forms of MS. TYSABRI increases the risk of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain that usually leads to death or severe disability. Patients should be monitored at regular intervals for any new or worsening signs or symptoms suggestive of PML. Because of the increased risk of PML, TYSABRI is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, alternate MS therapies. It is available in the US only through a restricted distribution program called the TOUCH Prescribing Program. According to product labeling, after two years, TYSABRI treatment led to a 67% relative reduction (p<0.001) in the annualized relapse rate compared to placebo and reduced the relative risk of disability progression by 42% (p<0.001). TYSABRI treatment also resulted in sustained and statistically significant reductions in brain lesion activity as measured by MRI. Changes in MRI findings often do not correlate with changes in the clinical status of patients (e.g., disability progression). The prognostic significance of the MRI findings in these studies has not been evaluated.

In the European Union, TYSABRI is indicated as a single disease-modifying therapy in highly active relapsing-remitting MS patients. Because of the increased risk of PML, it is for patients with high disease activity despite treatment with a beta-interferon or in patients with rapidly evolving severe relapsing-remitting MS. According to product labeling in the EU, after two years, TYSABRI treatment led to a 68% relative reduction (p<0.001) in the annualized relapse rate compared to placebo and reduced the relative risk of disability progression by 42-54% (p<0.001).

Serious adverse events that occurred in TYSABRI-treated patients included hypersensitivity reactions (e.g., anaphylaxis), infections, depression and gallstones. In MS trials, the incidence and rate of other serious and common adverse events, including the overall incidence and rate of infections, were balanced between treatment groups. Herpes infections were slightly more common in patients treated with TYSABRI. Serious opportunistic and other atypical infections have been observed in TYSABRI-treated patients, some of whom were receiving concurrent immunosuppressants. Common adverse events reported in TYSABRI-treated patients include headache, fatigue, infusion reactions, urinary tract infections, joint and limb pain, lower respiratory infections, rash, gastroenteritis, abdominal discomfort, vaginitis, and diarrhea.

For more information about TYSABRI please visit www.tysabri.com, www.biogenidec.com or www.elan.com, or call 1-800-456-2255.

(1) The relapse reduction rates used were: TYSABRI was 67%, AVONEX (Interferon beta-1a IM) 32%, Betaseron(R) (Interferon beta-1b) 34%, Copaxone(R) (glatiramer acetate) 29%, and Rebif(R) (Interferon beta-1a SC) 32%.

SOURCE: Biogen Idec and Elan Corporation, plc

http://www.elan.com/News/full.asp?ID=91301

New Data on TYSABRI® Presented at ECTRIMS Congress Demonstrate Significant Improvement in Cognitive Function in Patients with Multiple Sclerosis

28 September 2006

ZUG, Switzerland & DUBLIN, Ireland--(BUSINESS WIRE)--Sept. 28, 2006--Biogen Idec (NASDAQ: BIIB) and Elan Corporation, plc (NYSE: ELN) announced today that data from the Phase III AFFIRM monotherapy study demonstrated that treatment with TYSABRI® (natalizumab) significantly reduced the proportion of multiple sclerosis (MS) patients with worsening cognitive function as measured by the 3-second Paced Auditory Serial Addition Test (PASAT 3). These data, presented at the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Madrid, Spain, contribute to existing data which demonstrate the overall therapeutic benefits of TYSABRI, including its significant impact on relapse reduction, disability progression and MRI measures. TYSABRI has demonstrated a 68% relative reduction in the annualized relapse rate compared to placebo and a 42% reduction in the relative risk of disability progression, as published in the New England Journal of Medicine.

Cognitive deficits are under-recognized and often misdiagnosed as depression, stress or other personality disorders. Studies have shown that approximately 43% to 65% of MS patients show measurable cognitive impairment in formal testing.(1) Cognitive dysfunction can occur early in MS and in patients with relatively mild physical disability. These deficits have a substantial effect on the daily functioning of patients. Areas impacted by cognitive dysfunction include memory, ability to process information and learning. (1),(2)

The AFFIRM study was 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 and the rate of clinical relapses. Evaluating the effect of TYSABRI on cognitive function was a pre-specified endpoint of the AFFIRM study. Cognitive function was assessed using the 3-second Paced Auditory Serial Addition Test (PASAT 3), a test of auditory information processing. The study showed that treatment with TYSABRI reduced the risk of sustained cognitive worsening by 43% (p=0.013) when compared to placebo.

These cognitive function data complement the previously presented results of the AFFIRM study, which demonstrated a significant effect of TYSABRI on two-widely accepted health-related quality of life measures, the Short Form-36 Health Survey and the Visual Analogue Scale.

"Neuropsychological dysfunction significantly diminishes quality of life in many patients with multiple sclerosis, impacting everything from employment to social interaction. It is responsible for much hardship experienced by MS patients. The important positive effects of TYSABRI on cognitive functioning and quality of life add to the important benefits already reported on progression of disability and relapses. This provides strong evidence that observed neurologic benefits translate into important improvements as perceived by the patients," said Richard Rudick, MD, Director of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic.

 (1) Rao SM, et al. Neurology. 1991;41:685-691

(2) Amato MP, et al. Arch Neurol. 1995;52:168-172

SOURCE: Biogen Idec and Elan Corporation, plc

http://www.elan.com/News/full.asp?ID=910099

New Data on TYSABRI® Demonstrate Significant Effects on Health-Related Quality of Life Measures in Patients with Multiple Sclerosis

6 April 2006

SAN DIEGO--(BUSINESS WIRE)--April 6, 2006--

Data presented at American Academy of Neurology Annual Meeting also Show Impact on Measures of Visual Function and Disability Progression

Biogen Idec (NASDAQ: BIIB) and Elan Corporation, plc (NYSE: ELN) announced today that in Phase III multiple sclerosis (MS) studies TYSABRI® (natalizumab) showed significant effects on pre-specified health-related quality of life (QoL) measures, in addition to those previously reported on disability progression, relapse rate and MRI. Data presented this week at the annual meeting of the American Academy of Neurology in San Diego, CA also showed a significant impact on additional pre-specified measures of disability progression, including visual and cognitive function.

"MS is a debilitating disease that significantly reduces the quality of patients' lives by causing symptoms like fatigue, pain, and diminished emotional well-being. We have never before observed positive findings on our quality of life measures in a Phase III MS study. The TYSABRI study data show not only significant reductions in relapses and disability, but also suggest improved quality of life. This is very encouraging," said Richard Rudick, MD, Director of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic, who presented the QoL findings at the AAN meeting.

TYSABRI Shows Improvement in Quality of Life Assessments

In the two Phase III TYSABRI clinical trials, AFFIRM and SENTINEL, QoL was assessed using three different measures, the Multiple Sclerosis Quality of Life Inventory (MSQLI), the Short Form-36 Health Survey (SF-36), which is a component of the MSQLI, and a Visual Analogue Scale (VAS). The MSQLI is an MS-specific battery of 10 scales that measure disease impact on QoL including, fatigue, pain, sexual function, bowel and bladder function, visual impairment, mental health and need for social support. SF-36 is comprised of 36 questions designed to assess patients' physical and mental well-being. General well-being was also measured using the VAS.

In the AFFIRM monotherapy study, patients in the TYSABRI-treated group realized a significant improvement in physical measures of the SF-36 compared with a decline in the placebo-treated group (p=0.003). A significant improvement was also seen in the mental component of the SF-36 in patients treated with TYSABRI compared with a decline in the placebo-group (p=0.011). Significant benefits were also seen using the VAS (p=0.007). Improvements on quality of life measures were also observed in the SENTINEL study, in which TYSABRI was added to AVONEX® (Interferon beta-1a).

TYSABRI Impacts Measures of Visual Function

In another analysis of the AFFIRM and SENTINEL data, patients treated with TYSABRI had a reduction in the risk of visual decline as measured by contrast testing compared to control. Loss of visual function is one of the most common causes of disability and lower QoL in MS patients. Low contrast letter acuity was a pre-specified endpoint in both studies. Recent studies have demonstrated that low contrast letter acuity (perception of light gray letters of progressively smaller size on a white background) is a more sensitive measure of visual dysfunction in MS than traditional measures.

TYSABRI Impacts Measures of Disability Progression

The primary efficacy endpoint of AFFIRM and SENTINEL at two years was the rate of disability progression sustained for three months as measured by the Expanded Disability Status Scale (EDSS). Additional measures of disability included the Multiple Sclerosis Functional Composite (MSFC), which consists of three tests that evaluate ambulation, upper extremity dexterity and cognitive function.

In AFFIRM, treatment with TYSABRI led to a 42% reduction in the risk of disability progression compared to placebo (p=0.0002). TYSABRI was also associated with significant delay in progressing to EDSS of 4.0 (ambulatory with moderate disability) and 6.0 (requiring a cane, crutch or brace). TYSABRI treatment also had a significant impact on all subscales of the MSFC, including the Paced Auditory Serial Addition Test (PASAT), a measure of cognitive function (p=0.005).

TYSABRI Phase III Safety

Progressive multifocal leukoencephalopathy (PML), a rare and potentially fatal, demyelinating disease of the central nervous system has been reported in patients receiving TYSABRI. PML occurred in two MS patients who had received TYSABRI with AVONEX and in one Crohn's disease patient who had recently received an immunosuppressant. In placebo-controlled trials of TYSABRI in MS, the incidence and rate of other serious infections were balanced between TYSABRI-treated patients and controls. Serious infections reported in TYSABRI-treated patients included pneumonia, urinary tract infection and appendicitis. The overall incidence and rate of common infections were also balanced between treatment groups. Commonly reported infections included upper respiratory tract infections, influenza, urinary tract infections, and gastroenteritis. Herpes infections were slightly more common in patients treated with TYSABRI. The incidence and rate of other serious and common adverse events in clinical trials were similarly balanced between treatment groups. Serious events that occurred in TYSABRI-treated patients included hypersensitivity reactions, including systemic reactions, depression, and cholelithiasis. Common adverse events reported include infusion reactions, headache, fatigue, and arthralgia.

SOURCE: Biogen Idec and Elan Corporation, plc

http://www.elan.com/News/full.asp?ID=840112