Tysabri related Press Releases

Elan Issues Statement Regarding Federal Court Ruling on Tysabri(R) Collaboration Agreement

Calisha Myers — Fri, 04 Sep 2009 10:35:00 -0400

DUBLIN--(BUSINESS WIRE)--Sep. 3, 2009-- Elan Corporation, plc (NYSE:ELN) today issued the following statement regarding a ruling made by the United States District Court for the Southern District of New York that Elan has breached its Collaboration Agreement with Biogen Idec for the development and marketing of Tysabri:

We respect the Court's decision and the expedited attention in this matter. We are committed to working with Johnson & Johnson to close the transaction as quickly as possible, consistent with the Biogen-Elan Tysabri Collaboration Agreement.

About Elan

Elan Corporation, plc is a neuroscience-based biotechnology company committed to making a difference in the lives of patients and their families by bringing innovations in science to fill significant unmet medical needs. Elan shares trade on the New York and Dublin Stock Exchanges. For additional information about the company, please visit http://www.elan.com.

Forward Looking Statement

The statements in this press release that are not historical facts are forward-looking statements that involve risks and uncertainties. There can be no assurance that the proposed transaction with Johnson & Johnson can be restructured in a manner that will comport with the Court's ruling and the terms of the Biogen Idec Collaboration Agreement and be acceptable to Johnson & Johnson and Elan. Even if such a restructuring can be agreed to, the restructured deal may be on terms materially less favorable to Elan than those currently proposed. In addition, there can be no assurance as to when, or if, such a restructured transaction will complete. A further list and description of the risks, uncertainties and other matters that confront us can be found in our Annual Report on Form 20-F for the fiscal year ended December 31, 2008, and in our Reports of Foreign Issuer on Form 6-K filed with the U.S. Securities and Exchange Commission. We assume no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

BMRI DATA SHOWING TYSABRI PROMOTED REMYELINATION PRESENTED AT THE 61ST ANNUAL MEETING OF THE AMERICAN ACADEMY OF NEUROLOGY

Calisha Myers — Fri, 01 May 2009 10:09:20 -0400

BMRI DATA SHOWING TYSABRI PROMOTED REMYELINATION PRESENTED AT THE 61ST ANNUAL MEETING OF THE AMERICAN ACADEMY OF NEUROLOGY

Additional data suggests improvement in TYSABRI patients across clinical and patient-reported outcomes

Seattle, Wash. - April 28, 2009 - Biogen Idec (NASDAQ: BIIB) and Elan Corporation, plc (NYSE: ELN) today announced results of a study demonstrating that TYSABRI® (natalizumab) promoted regeneration and stabilization of damage done to the myelin sheath, as measured by advanced MRI technology. Damage to the myelin sheath causes the symptoms of multiple sclerosis (MS). Additional posters will also be presented during the Congress highlighting the ability of TYSABRI, in some patients, to improve physical function and patient reported outcomes on cognition, quality of life, and fatigue. TYSABRI is the first approved MS therapy with reported data suggesting that some of the signs of disease progression can be stopped. The strong efficacy profile demonstrated in clinical trials is enhanced further from these data and may help redefine success in MS.

"What we have seen in these MRI data suggest that TYSABRI may have the capacity to repair and possibly restore some of the damaged myelin sheath that protects nerve fibers. Results from this study support the continued investigation of the potential effects of TYSABRI on this process," said Robert Zivadinov, M.D., of the Jacobs Neurological Institute in Buffalo, N.Y., the lead investigator for the remyelination study.

"TYSABRI is changing the way neurologists and patients define success in the treatment of MS," said Michael Panzara, M.D., M.P.H., vice president and chief medical officer of neurology, Biogen Idec. "These MRI data presented at AAN provide early evidence that TYSABRI may not just slow the progress of MS, but may also be able to reverse the damage inflicted by the disease."

"Everyday, more patients understand that TYSABRI can represent a new way of looking at - and managing - their disease," stated Carlos Paya, M.D., Ph.D., president, Elan Corporation. "These latest analyses further build on the impressive data we have seen to date with TYSABRI."

TYSABRI helped stabilize and restore damage to the myelin sheath

The imaging study, which included a total of 110 subjects, used an advanced MRI technology called the Voxel-Wise MTR to measure lesions and normal brain tissue. The study showed that TYSABRI promoted remyelination when compared to those receiving interferon beta-1a IM and normal controls.

The effect of TYSABRI on lesions and NABT in relapsing MS was evaluated with a Voxel-Wise (VW) imaging method using magnetization transfer ratio (MTR). VWMTR is recognized as a powerful instrument for monitoring MS disease activity and effectiveness of therapeutic interventions in patients with MS.

In the study, 62 MS patients who received TYSABRI were followed for 12 months together with 26 MS patients who received interferon beta-1a IM and 22 age-matched and sex-matched normal controls. For each subject, baseline and follow-up MTR volume maps were placed in a common halfway-space. The resulting VW subtraction map was then enhanced via threshold-free cluster enhancement (TFCE) algorithm, and a significance threshold was determined based on subject-specific Monte Carlo simulation. Supra-threshold volumes (95th percentile) were quantified for both areas of increasing (remyelinating) and decreasing (demyelinating) MTR voxels, which represent a volume value.

There was no significant difference in decreasing VWMTR NABT volume over the follow-up between TYSABRI-treated and normal control groups. Relapsing-remitting patients on both therapies showed higher remyelination potential and less evident demyelination than relapsing secondary progressive patients. The volume of VWMTR changes in NABT (decreasing or increasing) was almost 3-5 times higher than the amount of changes observed for T2-lesion volume. This indicates that the VWMTR method might be a much more sensitive approach to capture demyelination/remyelination changes over time than the lesion-based volume measures.

The poster describing the study Natalizumab (Tysabri®) Promotes Remyelination in Patients with Multiple Sclerosis. A Voxel-Wise Magnetization Transfer Imaging Case-Control Study (P03.071) is available for viewing on Tuesday, April 28, 2009, at 4:00 p.m. PDT.

TYSABRI significantly increased the cumulative probability of achieving sustained improvement in disability in patients with relapsing MS

The poster describing the study Sustained Improvement in Physical Disability with Natalizumab in Patients with Relapsing Multiple Sclerosis (P06.131) will be available for viewing on Wednesday, April 29, 2009, at 4:00 p.m. PDT.

Data from this post-hoc analysis was previously presented at the 2008 World Congress on Treatment and Research in Multiple Sclerosis. The data showed TYSABRI produced significant results on the cumulative probability of sustained improvement in physical disability in those treated over two years compared with placebo. In patients with a baseline expanded disability status scale (EDSS) score ≥ 2.0, treatment with natalizumab significantly increased the probability of sustained improvement in disability by 69 percent relative to placebo. In the same patients, the probability of achieving sustained improvement was 29.6 percent with TYSABRI (n=417) compared with 18.7 percent with placebo (n=203) (p=0.006). In patients with an EDSS score ≥ 2.0 and highly active disease at baseline, the difference between groups was even greater, 35.5 percent for TYSABRI (n=103) and 15.4 percent for placebo (n=40) (p=0.045).

Patient-Reported Outcomes Study

In this study, patients with relapsing-remitting MS were asked after three months of treatment to rate their improvement, using validated outcomes tools. The posters presented at AAN show that overall, patients reported significant improvement in cognitive function, general and disease-specific health-related quality of life, and lower-levels of fatigue after the third infusion of TYSABRI. The ongoing one-year longitudinal study assesses health outcomes from the perspective of the patient before starting TYSABRI and at predetermined timepoints thereafter.

One of the posters, Early Effects of Natalizumab on Patient Reported Fatigue and Cognitive Function (P02.142) was made available for viewing on Tuesday, April 28 at 11:30 a.m. PDT and a second poster, Change in Health-Related Quality of Life in Multiple Sclerosis Patients Receiving Natalizumab (P05.144) will be available for viewing on Wednesday, April 29, 2009, at 11:30 a.m. PDT.

About TYSABRI

TYSABRI is a treatment approved for relapsing forms of MS in the U.S. and relapsing-remitting MS in the European Union. According to data that have been published in the New England Journal of Medicine, after two years, TYSABRI treatment led to a 68 percent relative reduction (p<0.001) in the annualized relapse rate compared to placebo and reduced the relative risk of disability progression by 42-54 percent (p<0.001).

In early 2008, TYSABRI was approved in the U.S. to induce and maintain clinical response and remission in adult patients with moderately to severely active Crohn's disease (CD) with evidence of inflammation who have had an inadequate response to, or are unable to tolerate, conventional CD therapies and inhibitors of TNF-alpha. According to the US full prescribing information, among patients who responded to TYSABRI, 54 percent sustain their response through every visit for one year compared to 20 percent of patients receiving placebo (p<0.001), for a treatment difference of 34 percent.

TYSABRI increases the risk of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain that usually leads to death or severe disability. Cases of PML have been reported in patients taking TYSABRI who were recently or concomitantly treated with immunomodulators or immunosuppressants, as well as in patients receiving TYSABRI as monotherapy. Other serious adverse events that have occurred in TYSABRI-treated patients included hypersensitivity reactions (e.g., anaphylaxis) and infections. Serious opportunistic and other atypical infections have been observed in TYSABRI-treated patients, some of whom were receiving concurrent immunosuppressants. Herpes infections were slightly more common in patients treated with TYSABRI. In MS and CD clinical trials, the incidence and rate of other serious adverse events, including serious infections, were similar in patients receiving TYSABRI and those receiving placebo. Common adverse events reported in TYSABRI-treated MS patients include headache, fatigue, infusion reactions, urinary tract infections, joint and limb pain and rash. Other common adverse events reported in TYSABRI-treated CD patients include respiratory tract infections and nausea. Clinically significant liver injury has been reported in patients treated with TYSABRI in the post-marketing setting.

TYSABRI is approved in more than 40 countries.

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

About Biogen Idec

Biogen Idec creates new standards of care in therapeutic areas with high unmet medical needs. Founded in 1978, Biogen Idec is a global leader in the discovery, development, manufacturing, and commercialization of innovative therapies. Patients in more than 90 countries benefit from Biogen Idec's significant products that address diseases such as lymphoma, multiple sclerosis, and rheumatoid arthritis. For product labeling, press releases and additional information about the company, please visit www.biogenidec.com.

About Elan

Elan Corporation, plc is a neuroscience-based biotechnology company committed to making a difference in the lives of patients and their families by dedicating itself 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.

EU Panel Recommends Update For Elan, Biogen's Tysabri Label

Calisha Myers — Fri, 26 Sep 2008 12:00:34 -0400

EU Panel Recommends Update For Elan, Biogen's Tysabri Label

ZURICH -(Dow Jones)- European Medicines Agency, an advisory body to the European drugs regulator, said Thursday it recommends an update of product information of multiple-sclerosis drug Tysabri, marketed by Biogen Idec (BIIB) and Elan Corp Plc ELN) to include risk of progressive multifocal leukoencephalopathy

The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended that the product information for Tysabri (natalizumab) be updated to further increase awareness about the risk of progressive multifocal leukoencephalopathy (PML) in patients with relapsing-remitting multiple sclerosis (MS) who have been treated with the medicine.

PML is a rare brain infection whose symptoms are similar to those of an MS attack. The CHMP's recommendation follows the reporting in July of two new cases of PML in patients who had been treated for MS with Tysabri alone for more than 12 months.

Following a review of the available data, the Committee concluded that the benefits of Tysabri continue to outweigh its risks in the treatment of relapsing-remitting MS, but that the existing warning on the risk of PML should be strengthened to heighten patients' and prescribers' awareness about this rare but serious side effect.

In addition, the Committee requested an update to the 'Physician Information and Management Guidelines for Multiple Sclerosis Patients on Tysabri'. These guidelines are part of the agreed risk management plan for Tysabri, which set out a series of risk minimisation measures. Following the update, doctors will be able to obtain more detailed guidance on how to differentiate PML from a relapse of MS, and how to manage suspected cases of PML.

The CHMP's recommendation will now be sent to the European Commission for the adoption of a decision.

EMEA Web Site: http://www.emea.europa.eu

TYSABRIÂ® DEMONSTRATES SUSTAINED IMPROVEMENT IN FUNCTIONAL OUTCOMES IN MULTIPLE SCLEROSIS PATIENTS ACCORDING TO NEW POST-HOC ANA

Calisha Myers — Mon, 22 Sep 2008 11:28:55 -0400

TYSABRI® DEMONSTRATES SUSTAINED IMPROVEMENT IN FUNCTIONAL OUTCOMES IN MULTIPLE SCLEROSIS PATIENTS ACCORDING TO NEW POST-HOC ANALYSIS

TYSABRI is the Only Marketed MS Treatment to Show Both Significant Slowing in Disability Progression and Sustained Improvement in Physical Disability

Montreal, Canada - September 19, 2008 - Biogen Idec (NASDAQ: BIIB) and Elan Corporation, plc (NYSE: ELN) announced that a post-hoc analysis showed TYSABRI® (natalizumab) treatment increases the probability of achieving sustained improvement in physical disability over two years when compared to placebo. This post-hoc analysis provides the first evidence that TYSABRI is associated with a significant improvement in functional outcome, rather than only slowing or preventing progression of disability, in those living with relapsing multiple sclerosis (MS). These findings were derived from a subset analysis of the Phase III AFFIRM trial and were presented today as a poster presentation at the World Congress on Treatment and Research in Multiple Sclerosis in Montreal, Canada. This is the first joint meeting of the Americas Committee on Treatment and Research in Multiple Sclerosis (ACTRIMS) and its counterparts in Europe and Latin America: ECTRIMS and LACTRIMS.

"These results show that TYSABRI treated patients are significantly more likely to experience a sustained improvement in disability compared to placebo patients. This finding from a post-hoc analysis of the pivotal AFFIRM trial supports both the earlier findings from the AFFIRM trial that TYSABRI is associated with an improvement in quality of life as well as anecdotal evidence of recovery of function in some patients." said Frederick E. Munschauer, MD, Smith Professor and Chair, Department of Neurology, State University of New York at Buffalo. "While, like TYSABRI, other therapies have shown a slowing of progression in disability, this analysis represents the first evidence supporting a sustained improvement in function associated with an approved disease modifying therapy."

Post-hoc Disability Analysis of Phase III AFFIRM Study

The proportion of patients exhibiting sustained improvements in physical disability in the AFFIRM study was determined based upon the Expanded Disability Status Scale (EDSS) over two years in patients with relapsing MS. EDSS is one of the oldest and most widely utilized methods of quantifying disability in MS.

Post-hoc analysis of AFFIRM patients assessed sustained improvement in disability among patients with a baseline EDSS score ≥ 2.0. Improvement in disability was defined as a one-point decrease in EDSS score sustained for 12 weeks. The cumulative probabilities of 12-week sustained improvement in disability at two years were estimated using the Kaplan-Meier method. Treatment effects were analyzed using the Cox proportional hazards model adjusted for baseline EDSS score. The distribution of sustained improvement by baseline EDSS score for each treatment group was also examined.

TYSABRI produced significant results on the cumulative probability of sustained improvement in disability in those treated over two years compared with placebo. In patients with a baseline EDSS score ≥ 2.0, the probability of achieving sustained improvement was 29.6% with TYSABRI (n=417) compared with 18.7% with placebo (n=203) (p=0.006). In patients with an EDSS score ≥ 2.0 and highly active disease at baseline, the difference between groups was even greater, 35.5% for TYSABRI (n=103) and 15.4% for placebo (n=40) (p=0.045).

The submitted abstract for this study, entitled "Natalizumab significantly increases the cumulative probability of sustained improvement in physical disability" (ID #P474), is available on the World Congressâ€^TM website.

About TYSABRI

TYSABRI is a treatment approved for relapsing forms of MS in the US and relapsing-remitting MS in the European Union. According to data that have been published in the New England Journal of Medicine, 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).

TYSABRI was approved in early 2008 to induce and maintain clinical response and remission in adult patients with moderately to severely active Crohn's disease (CD) with evidence of inflammation who have had an inadequate response to, or are unable to tolerate, conventional CD therapies and inhibitors of TNF-alpha. According to the US full prescribing information, among patients who responded to TYSABRI, 54% sustain their response through every visit for one year compared to 20% of patients receiving placebo (p<0.001), for a treatment difference of 34%.

TYSABRI is approved in more than 35 countries. At the end of June 2008, more than 31,800 patients were on commercial and clinical TYSABRI therapy worldwide. Patients on TYSABRI therapy have continued to increase. An update will be provided in October in conjunction with Biogen Idec's third quarter earnings release.

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

About Elan

About Biogen Idec

First Multiple Myeloma Patient Treated

Calisha Myers — Fri, 05 Sep 2008 11:43:50 -0400

Elan and Biogen Idec Initiate First Clinical Trial of TYSABRI® in Oncology

First Multiple Myeloma Patient Treated

CAMBRIDGE, Mass. & DUBLIN, Ireland--(BUSINESS WIRE)--Sept. 5, 2008--Elan Corporation, plc (NYSE: ELN) and Biogen Idec (NASDAQ: BIIB) today announced the initiation of the first clinical trial of TYSABRI(R) (natalizumab) in oncology. The first dose of TYSABRI was administered yesterday in the trial. The objectives of this Phase I/II study are to evaluate the safety and potential anti-tumor activity of TYSABRI in patients with relapsed or refractory multiple myeloma. TYSABRI is a recombinant, humanized monoclonal antibody that targets the adhesion molecule VLA4 (also known as alpha-4 integrin) that is expressed on the surface of many types of immune cells. VLA4 is also found on the surface of multiple myeloma cells and may be involved in their survival.

"We are excited to initiate the oncology clinical trial program for TYSABRI," said Wayne Saville, MD, Director, Oncology Medical Research at Biogen Idec. "TYSABRI has potential in multiple myeloma and a number of other cancers through its action as a blocker of VLA4. It is a meaningful addition to Biogen Idec's robust oncology pipeline."

"This clinical trial in oncology represents an opportunity for TYSABRI to continue to address unmet medical needs, potentially bringing new therapeutic options to patients and their oncologists," said Gordon Francis, MD, Senior Vice President, Global Clinical Development at Elan Pharmaceuticals, Inc.

About the Trial

This Phase I/II, open-label, two-arm study is designed to evaluate the safety and anti-tumor activity of TYSABRI in patients with relapsed or refractory multiple myeloma. In the Phase I portion of the trial, a standard dose-escalation design will be used to assess the safety and tolerability of TYSABRI in up to 12 patients. In the Phase II portion of the study, up to 30 patients will be randomized to the tolerated doses identified in Phase I of the study.

Treatment cycles will consist of intravenous infusions of TYSABRI once every 28 days for 6 months. After 6 months, if the patient has achieved a partial or a complete response, he or she may continue to receive TYSABRI once every 28 days until progression of disease occurs.

Patients eligible for the study must be at least 18 years of age with relapsed or refractory multiple myeloma who have failed or cannot tolerate therapy with bortezomib and thalidomide or lenalidomide.

About Multiple Myeloma

Multiple myeloma is a cancer of the plasma cell, an important part of the immune system that produces antibodies to help fight infection and disease. Certain immune cells, called B cells, change into plasma cells when they respond to an antigen, producing antibodies to attack bacteria and viruses. However, when plasma cells multiply in an uncontrolled way, they can produce tumors, which generally develop in the bone marrow. These plasma cells produce excessive amounts of antibodies and can interfere with normal blood-forming functions of the bone marrow, crowding out healthy cells and leaving patients susceptible to anemia, hemorrhage, infection and severe osteoporosis.

Multiple myeloma is the second most common blood cancer in the United States (US). More than 50,000 people in the US are living with multiple myeloma, and about 20,000 new cases are expected to be diagnosed this year. Nearly 11,000 Americans are expected to die from the disease this year. Men are 50 percent more likely to develop the disease than women. Other risk factors include race, radiation exposure, family history, occupational exposure to petroleum, obesity and other plasma cell disorders.

About TYSABRI

TYSABRI is a treatment approved for relapsing forms of MS in the United States and relapsing-remitting MS in the European Union. According to data that have been published in the New England Journal of Medicine, 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).

TYSABRI was recently approved to induce and maintain clinical response and remission in adult patients with moderately to severely active Crohn's disease (CD) with evidence of inflammation who have had an inadequate response to, or are unable to tolerate, conventional CD therapies and inhibitors of TNF-alpha.

TYSABRI is approved in more than 35 countries.

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

About Elan

About Biogen Idec

Safe Harbor/Forward-Looking Statements

This press release contains forward-looking statements regarding the potential use of TYSABRI. These statements are based on the companies' current beliefs and expectations. The development of TYSABRI in new indications and its commercial potential are subject to a number of risks and uncertainties. Factors which could cause actual results to differ materially from the companies' current expectations include but are not limited to the risk that we may be unable to adequately address concerns or questions raised by FDA or other regulatory authorities, that concerns may arise from additional data, that the incidence and/or risk of PML or other opportunistic infections in patients treated with TYSABRI may be higher than observed in clinical trials, or that the companies may encounter other unexpected hurdles. Drug development and commercialization involves a high degree of risk.

For more detailed information on the risks and uncertainties associated with the companies' drug development and other activities, see the periodic and current reports that Biogen Idec and Elan have 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.

FDA Updates the Information for Healthcare Professionals Sheet for Tysabri (natalizumab)

Calisha Myers — Tue, 26 Aug 2008 08:51:51 -0400

FDA Updates the Information for Healthcare Professionals Sheet for Tysabri (natalizumab)

Information for Healthcare Professionals Natalizumab Injection for Intraveneous Use (marketed as Tysabri)

ROCKVILLE, Md., Aug. 25, 2008--FDA ALERT [8/2008]: The FDA has recently received information from the manufacturer about two new cases of progressive multifocal leukoencephalopathy (PML) in patients receiving Tysabri monotherapy for multiple sclerosis in Europe. Both patients had received Tysabri for more than one year. PML, which is usually fatal, is a known risk of Tysabri treatment, but previous cases in patients with multiple sclerosis were seen in combination with other immunomodulatory therapies. About 39,000 patients have received treatment with Tysabri worldwide, with about 12,000 patients having been treated for at least one year. No new cases have been seen in the US, where about 7,500 patients have received the drug for longer than one year and about 3,300 patients have received the drug for at least one and a half years.

In the U.S., Tysabri is available only to patients with relapsing multiple sclerosis (MS) or Crohn's disease (CD) who are enrolled in the risk minimization plan called the TOUCH Prescribing Program. Under the TOUCH Prescribing Program, every Tysabri-treated patient is closely monitored and followed for the occurrence of PML and other serious opportunistic infections.

While the two patients who developed PML were on monotherapy, the FDA still believes that Tysabri monotherapy may confer a lower risk of PML than when Tysabri is used together with other immunomodulatory medications.

The FDA is working with the manufacturer to amend the product labeling to inform prescribers and patients that cases of PML have occurred in patients taking Tysabri as monotherapy.

This information reflects FDA's current analysis of data available to FDA concerning this drug. FDA intends to update this sheet when additional information or analyses become available.

To report any serious adverse events associated with the use of this drug, please contact the FDA MedWatch program and complete a form online at http://www.fda.gov/medwatch/report.htm or report by faxing (1-800-FDA-0178), by mail using the postage-paid address form provided online, (5600 Fishers Lane, Rockville, MD 20852-9787), or by telephone (1-800-FDA-1088).

Recommendations and Information for Healthcare Professionals registered with the TOUCH Prescribing Program to Consider when Prescribing Tysabri

* The two new cases of PML are notable for being the first cases occurring in the absence of concomitant or recent immunomodulatory therapy (e.g., beta-interferons)

* Although PML and other opportunistic infections are known risks of Tysabri, these are the first cases of PML that have been reported following Tysabri's market re-introduction in June 2006.

* PML is a rare infection of the central nervous system caused by a virus that can affect patients who have a compromised immune system.

* Both of the recently diagnosed patients were receiving Tysabri as monotherapy (one for 14 months and one for 17 months), although one of the patients had a history of prior immunosuppressant therapy with azathioprine and beta-interferons.

* Both patients were diagnosed on the basis of physical findings, MRI findings, and the detection of JC viral DNA in the cerebrospinal fluid.

* The incidence of PML with Tysabri remains unknown, although the available data indicate that the risk of PML when Tysabri is taken as monotherapy is lower than the risk of PML when Tysabri is taken with other immunosuppressant MS treatments.

* Continued clinical vigilance and close monitoring for the signs and symptoms of PML as dictated by the TOUCH Prescribing Program is necessary.

* Tysabri should not be infused if PML is suspected.

Information for Healthcare Professionals and Patients to Consider

* Always talk to your doctor about any medications and over the counter supplements that you may be taking.

* If you and your doctor decide that the benefits of starting Tysabri outweigh possible risks, then you must be enrolled in the TOUCH Prescribing Program before receiving Tysabri. The TOUCH Prescribing Program materials will describe the signs and symptoms of PML you should watch for.

* PML is a rare infection of the brain caused by a polyomavirus, called the JC virus. The JC virus is often acquired during childhood. Most adults have been infected with the JC virus but do not develop PML. The virus appears to remain inactive until something (such as a weakened immune system) allows it to be reactivated and start to multiply. People with a weakened immune system or people taking drugs that suppress their immune system (immunosuppressants) are most likely to get the disease. This virus infects the patient's brain and nervous system when their immune system is not working optimally.

* PML can occur naturally in the course of certain diseases, and it may also occur if someone's immune system has been suppressed by medications. Tysabri is one of the medications that PML has been associated with. Symptoms of PML may be similar to MS, so the diagnosis of PML is made by brain MRI and detection of the virus in the spinal fluid.

* PML symptoms may begin gradually, but they usually worsen rapidly. Symptoms vary depending on which part of the brain is infected. In about two-thirds of patients mental function declines rapidly and progressively, causing dementia. Speaking becomes increasingly difficult. People may become partially blind. Walking may become difficult. Rarely, headaches and seizures occur.

* The two new cases of PML are notable for being the first cases in patients with multiple sclerosis treated with Tysabri who were not also taking beta-interferon therapy.

* Both patients were diagnosed on the basis of physical findings, abnormal MRI findings and the detection of JC viral DNA in the cerebrospinal fluid.

* The risk of developing PML with Tysabri remains unknown, although the available data indicate that the risk of PML when Tysabri is taken as monotherapy is lower than the risk of PML when Tysabri is taken with other treatments that affect your immune system.

* Tysabri should not be given if PML is suspected until further clinical evaluation is performed.

Background and Data Summary

Tysabri, a recombinant humanized monoclonal antibody that binds to α4-integrin, was initially approved by the FDA in November, 2004, but was withdrawn by the manufacturer in February 2005 after three patients in clinical trials (two in MS trials and one in a CD trial) developed PML. The two MS patients were receiving concomitant beta-interferon therapy, and the patient in the CD trial had received immosuppressive therapy prior to receiving Tysabri.

In June 2006, the FDA approved an application for the re-marketing of Tysabri as monotherapy for the treatment of patients with relapsing forms of MS. Tysabri is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, alternate multiple sclerosis therapies.

In January 2008, Tysabri was approved for inducing and maintaining a clinical response and remission in patients with moderate to severely active CD who have had an inadequate response to, or are unable to tolerate, conventional CD therapies and inhibitors of TNF-α.

The European cases of PML were reported by Biogen Idec and Elan (the makers and marketers of Tysabri) as follows:

* Case 1: This postmarket case of PML occurred in a patient who had received Tysabri monotherapy for 17 months. Prior to treatment, the patient had aggressive MS with high levels of relapse and MRI activity. Signs and symptoms which led to a suspicion of PML included muscle twitching, weakness of the left upper extremity, and brain MRI changes. Tysabri dosing was suspended and the patient underwent cerebrospinal fluid (CSF) testing. The patient has been diagnosed with PML based on the detection of JC viral DNA in the CSF in the setting of these clinical symptoms and MRI findings. Follow up to the case, received by the company on July 31, 2008, reported that this patient is ambulatory and continues to be managed as an outpatient.

* Case 2: This postmarket case occurred in a patient who had received Tysabri monotherapy for 14 months. This patient with MS had a long history of treatment with disease-modifying therapies including azathioprine and beta-interferons. Initial clinical features of PML included development of hemiparesis and cognitive symptoms. Brain MRI revealed lesions that were atypical. The diagnosis of PML was confirmed when JC viral DNA was detected in the CSF in the setting of the appropriate clinical signs, symptoms, and MRI features. At the time of reporting, the patient was hospitalized and in stable condition.