By Thomas Gryta Of DOW JONES NEWSWIRES NEW YORK -(Dow Jones)- Biogen Idec Inc. (BIIB) reported that there were no new cases of a rare brain infection in users of its multiple sclerosis drug Tysabri in the first of its planned weekly Web-based updates on Friday.

The Cambridge, Mass., biotech, which sells Tysabri with Ireland's Elan Plc (ELN), will post the updates in an effort to more consistently disclose incidences of the often fatal condition.

A suspected link to progressive multifocal leukoencephalopathy, or PML, led to Tysabri being pulled from the market for 18 months beginning in 2005. Since the relaunch, the company has reported that four people had confirmed cases of PML, with one dying.

This past summer marked the two-year anniversary of Tysabri's re-launch, raising Wall Street's anxiety over PML-related news. The timeline is important because two patients with PML in 2005 were using the drug for more than two years.

Biogen will post an update of PML cases on the investor relations section of its Web site every Friday at 4:30 p.m. EST and will continue to do so until July 24, which is the third anniversary of the drug's relaunch.

"I think it is going to provide a lot of clarity and almost realtime information to the market to really make decisions and evaluate the situation," said Citigroup analyst Yaron Werber.

Werber has criticized Biogen's former policy of disclosing new cases through 8-K filings with the Securities and Exchange Commission as making investors nervous and pressuring the company's shares.

Biogen's stock, which closed up 30 cents, or 0.6%, at $48.25, is down 17% for the last 12 months.

Elan closed Friday down 31 cents, or 3.6%, at $8.39 and is down 67% in the last year. Tysabri is Elan's biggest seller, making it more sensitive to related news, plus it was hurt by disappointing data over the summer from an Alzheimer's disease drug in development with Wyeth (WYE).

Werber expects the regular updates to help ease of the "fear of the unexpected" in Biogen shares. He agrees with stopping the disclosures in late July, when a clear picture of the PML risk in Tysabri should be firmly established. "

At some point they would be wise to cut this off," he said. "Because this sort of information is going to be very good for the competition. You can't go on marketing a product in this situation forever."

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	Penn Researchers Find Treatment for MS also Reduces Vision Loss in MS Patients
	First MS Study to Include a Test of Visual Function
		> Researchers at the University of Pennsylvania School of Medicine have found that natalizumab (TYSABRI®) – a drug that slows disability and reduces relapse rates in patients with multiple sclerosis (MS) – also reduces vision loss in patients with relapsing MS.  > Researchers found vision loss – a worsening of vision defined as a two-line (10-letter) reduction in letter chart scores – was reduced by as much as 47% among people taking natalizumab, compared to those taking placebo.  > The study appears in the April 17 issue of Neurology. (PHILADELPHIA) – According to a study that appears in the April 17 issue of Neurology, researchers at the University of Pennsylvania School of Medicine have found that natalizumab (TYSABRI®) – a drug that slows disability and reduces relapse rates in patients with multiple sclerosis (MS) – also reduces vision loss in patients with relapsing MS.  Vision loss is one of the most common and disabling symptoms of MS. "Not only does natalizumab prevent the worsening of vision loss in people with relapsing MS, but it is also associated with significant reductions in the likelihood of sustained vision loss due to inflammatory demyelination of nerve fibers that connect to the eye, a common cause of visual loss in MS," says Laura J. Balcer, MD, MSCE, Associate Professor of Neurology and Ophthalmology at Penn, and lead author of the paper.  Using low-contrast letter acuity charts, researchers found vision loss – a worsening of vision defined as a two-line (10-letter) reduction in letter chart scores – was reduced by as much as 47% among people with MS taking natalizumab, compared to those taking placebo. Image Courtesy: Precision Vision, LaSalle IL The researchers analyzed data from two randomized, double-blind, placebo-controlled, parallel group, phase 3 clinical trials involving 2,138 men and women with relapsing MS from clinical centers in Europe, North America, Australia, and New Zealand.  More than half of the participants received natalizumab every four weeks for two years, while the remaining participants received placebo.  Visits were conducted every 12 weeks and visual function testing was performed at each study visit.  Low-contrast letter acuity was measured using low-contrast letter charts (eye charts with gray letters on a white background). Researchers found vision loss – a worsening of vision defined as a two-line (10-letter) reduction in letter chart scores – was reduced by as much as 47% among people taking natalizumab, compared to those taking placebo.  "Not only do the findings of the study add to our understanding of the effects of natalizumab, but the results provide strong validation for a simple, sensitive, cost-effective, and clinically meaningful measure of visual function in MS," advises Dr. Nicholas LaRocca, Associate Vice President, Health Care Delivery and Policy Research at the National MS Society. The researchers caution that, as with any therapy, the benefits of natalizumab must be considered in the context of potential risks or complications.  In the case of natalizumab, three confirmed cases of progressive multifocal leukoencephalopathy (PML) – a rare, often lethal brain disease – have been reported. Despite the fact that vision loss is a common and important cause of disability in MS, the natalizumab clinical trials were the first to include a test of visual function.  These trials showed that low-contrast letter acuity eye chart testing is an effective measure for assessing visual outcomes, and may be useful in future clinical trials. This study was supported by Biogen Idec and Elan, makers of natalizumab.  Dr. Balcer has received support for consulting from Biogen Idec as well as from other companies for work on developing visual outcome measures for MS clinical trials.

TYSABRI: "Biologic treatment for MS offers hope": Daytona Beach News-Journal

December 18, 2006

Biologic treatment for MS offers hope
By DR. YONG H. TSAI

Susan awoke one day with blurred, obstructed vision along with dizziness and numbness in her legs. A trip to her doctor's office triggered an order for blood tests and an MRI. She was diagnosed with multiple sclerosis (MS), an autoimmune disease involving the central nervous system.

Our brain and spinal cord, that house the main pathway of our body's nerve signals, offer a layer of insulation, called myelin, that surrounds and protects these nerve cells.

Like a plastic cover that surrounds the many wires of an electric cable, myelin covers nerve fibers to ensure that the nerve signals have safe, uninterrupted passage.

With MS, myelin sheaths break down (demyelination), due to inflammation caused by the autoimmune process. Damaged tissue eventually turns into scar tissue (sclerosis), meaning "multiple sclerosis."

Classic symptoms of MS include numbness, visual disturbance, abnormal gait, imbalance, muscle weakness or spasm, urinary incontinence, vertigo, slurred speech and even pain.

There are several forms of MS. Relapsing-remitting MS (RRMS) occurs about 25 percent of the time with intermittent relapses, including worsening of existing symptoms or the development of new ones.

Over the course of 10 to 15 years, more than 50 percent of RRMS will evolve into progressive MS, known for more frequent relapses, incomplete remission bouts and general overall deterioration.

During the past few years, beta interferons such as Avonex, Rebif, Betaseron and Glatiramer acetate, by modifying the inflammatory process, have been used to treat MS.

However, all still have side effects and some have poor results. In November 2005, Natalizumab (Tysabri), a biologic agent, was proven to block the function of key molecules. The process could transport immune cells crossing the brain and blood barrier (BBB), and prevent against an attack on one's central nervous system.

Clinical trials have shown Tysabri, administered by monthly intravenous infusion, is a very effective therapy in reducing relapses and decreasing new brain lesions.

However, the shocking news surfaced Feb. 28 that Tysabri was suspended temporarily from commercial distribution due to three serious, adverse events. Multifocal leukoencephalopathy (PML) occurred in clinical trial patients treated with Tysabri plus Avonex.

However, there have been no reports of PML in patients treated with either Tysabri or Avonex alone.

More recently, Tysabri has been permitted for MS treatment. Tysabri is only indicated as a single-agent treatment instead of in combined therapy with Avonex or other agents. It's for patients with the relapsing form of MS and poor response to traditional treatments.

Though there is some concern with rare side effects of Tysabri, this new biologic agent offers new hope.

Tysabri helps cognition - United Press International

ZUG, Switzerland, Sept. 28 (UPI) -- U.S. firm Biogen Idec and Irish firm Elan said Thursday new data show multiple-sclerosis drug Tysabri helps cognitive ability in MS.

The companies said phase 3 data from the AFFIRM study showed Tysabri "significantly reduced the proportion of MS patients with worsening cognitive function as measured by the 3-second Paced Auditory Serial Addition Test (PASAT 3)."

Specifically, the two-year AFFIRM study, enrolling 942 MS patients at 99 sites worldwide, showed the treatment reduced the risk of sustained cognitive worsening by 43 percent, compared to placebo.

"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," Richard Rudick, director of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic, said in a statement issued by the companies.

The results were presented this week at the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Madrid, Spain.

Earlier data on Tysabri showed the drug reduced by 68 percent MS relapse, compared to placebo, and cut by 42 percent the relative risk of disability progression. The therapy has U.S. approval as a monotherapy treatment for relapsing forms of MS.

Elan Extends Tysabri's Reach to Canada [more]
...To put this in perspective, Canada has possibly the highest rate of MS in the whole world. An estimated 55,000 to 75,000 Canadians suffer from the disease -- that's nearly one-fifth the estimated number of patients in the United States.

The fortunes of Elan will rise and fall with the prospects of Tysabri. When the drug was taken off the market early last year, many investors pegged the company for bankruptcy because of its high debt load. Now that the drug has been approved for sale again in the U.S. and also for marketing in the EU, Elan has a chance to start making enough money to stem the company's losses and hopefully begin paring down some of the nearly $2 billion in debt that will be due in varying amounts in 2008 and 2011.....

"MS drug Tysabri back, but only under strict guidelines"
Lindsey Wolf, 49, took the drug for several months two years ago and began taking it again a month ago...'Back then I found it was really helping me from getting worse,' Mr. Wolf said. 'I haven't really noticed anything yet (this time) because I only tried it once. I'm going to wait and see this next time to see how I do next month. I think it will be a pretty good drug........'

TYSABRI 'watched like a hawk': Angelia McCoy hopes she can feel like 'Wonder Woman' again as a test subject....FULL STORY.
"Angelia McCoy waits for registered nurse Judi Greene to administer an infusion of Tysabri, a drug for multiple sclerosis recently re-released after its manufacturer pulled it off the market 1 1/2 years ago amid safety concerns....

Earlier this summer, federal regulators approved the company's plan to reintroduce Tysabri under strict limits. The rules say that it can only be used for people whose multiple sclerosis can't be controlled with other drugs. Also, patients may not take other medications while they are on Tysabri.Before each monthly treatment, they must fill out four surveys that track how they are faring physically and mentally. 'Do you have difficulty understanding what others are saying, or expressing yourself?' one survey asks. 'Do you have any weakness or numbness in your legs?'Each survey must be faxed to the drug manufacturer. A 'yes' answer to any of the questions would lead to an interruption in treatment while doctors check the patient for complications.The drug costs about $25,000 per year, but McCoy's is covered by the manufacturer because she is taking part in

US doctors still wary of Elan drug TYSABRI- survey
US doctors are proving more wary than many had expected about prescribing Elan's multiple sclerosis drug Tysabri, which was relaunched in July after being suspended because of safety concerns.

Over the past month or so, analysts have drawn down their 2006 sales forecasts as it becomes clear that doctors wary of the risk of the rare but potentially fatal brain disease PML are reserving the drug as a treatment of last resort.

The drug, which is made by Elan and its US Biogen Idec, had been expected by some analysts to generate sales this year of more than $100m, but those figures have dropped dramatically.

Ian Hunter, an analyst at Goodbody stockbrokers, said yesterday that he has cut his full-year Tysabri forecast to $25.7m from $78m, partly because of continuing safety concerns and the complexity of reimbursement systems in Europe.

A survey of 63 US neurologists indicates that in 2006 Tysabri will be used in less than 1% of multiple sclerosis patients - translating into revenue of under $30m.

Since July, only 47 of more than 8,500 patients treated by US physicians surveyed had used Tysabri, even though more than 700 patients had discussed using it, according to the report.

And more than 75% of the patients who had used Tysabri prior to its 2005 suspension have decided not to use it since its reintroduction..... MORE

2,800 have registered for Tysabri
In the United States, where Biogen Idec manufactures the drug and Elan distributes it, US$5.4 million (4.3 million) of Tysabri was sold to 1,700 patients, while another 2,800 have registered for potential treatment.

Crohn's Disease...Elan Press Release: TYSABRI® Maintained Remission in Patients with Moderate-to-Severe Crohn's Disease Treated for Longer Than Two Years According to Data Presented This Week Article
TYSABRI Data Support Maintenance Efficacy In Patients Who Had Previously Failed Infliximab Therapy

DUBLIN, Ireland & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Oct. 24, 2006--Elan Corporation, plc (NYSE:ELN) and Biogen Idec (NASDAQ:BIIB) announced today data that show TYSABRI® (natalizumab) maintained remission in Crohn's disease patients (CD) treated for longer than 2 years. These data, presented this week at the 14th United European Gastroenterology Week (UEGW) in Berlin, Germany, and at the Annual American College of Gastroenterology (ACG) in Las Vegas, Nevada, were part of an open label extension study of patients who participated in the ENACT-2 trial.

Ninety-three percent (93%) of TYSABRI patients who were in remission at month 12 of ENACT-2, were still in remission following 6 additional TYSABRI infusions in the open-label extension study (OLE) and 86% were still in remission after 12 additional infusions.

"What is truly exciting is that patients who enter remission on TYSABRI may remain in remission in the long-term without loss of efficacy over time. These data are a significant advance for the field and suggest that TYSABRI may be an alternative biologic outside the anti-TNF class for patients suffering from Crohn's disease," said Remo Panaccione MD, Director, Inflammatory Bowel Disease Clinic, University of Calgary, Calgary, Canada, who presented the data at UEGW.Click Here for Complete Elan Press Release

TYSABRI: New Pharmacoeconomic Data on TYSABRI® Demonstrate Significant Reduction in Steroid Use and Hospitalizations in Patients with Multiple Sclerosis [click for more] 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)).......

Tysabri helps cognition - United Press International ....the treatment reduced the risk of sustained cognitive worsening by 43 percent, compared to placebo.....

Tysabri helps cognition - United Press International ....the treatment reduced the risk of sustained cognitive worsening by 43 percent, compared to placebo.....

Analyst Worries About Tysabri: "Tysabri, the multiple sclerosis treatment from Elan appears to be getting hit by the strict safety rules that accompanied the drug's reapproval by regulators, according to one analyst.

Deborah Knobelman of the research firm Piper Jaffray slashed her estimate for worldwide Tysabri sales to $21 million for this year, down from her previous $123 million expectation. According to her feedback from doctors, physicians' adoption rates of the drug were slower than she had anticipated in the U.S. because of safety concerns, reimbursement procedures and patient-monitoring requirements......

Natalizumab (Tysabri) Reduces Brain Atrophy, Improves Cognition During Second Year of Multiple Sclerosis Treatment
MADRID, SPAIN -- September 30, 2006 -- Natalizumab (Tysabri) significantly reduces brain atrophy compared with placebo treatment during the second year of treatment and significantly improves cognitive function in patients with multiple sclerosis (MS), researchers reported here at the 22^nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIM).

"We saw that natalizumab was, indeed, effective in reducing the rate of brain atrophy in the second year of treatment, and this is especially important because in the brain of an MS patient, brain atrophy correlates to reduced cognitive function," said presenting investigator Elizabeth Fisher, PhD, assistant professor, department of biomedical engineering, Cleveland Clinic, Cleveland, Ohio.....

The investigators also found that natalizumab treatment significantly reduced the proportion of patients with worsening in 3-second Paced Auditory Serial Addition Test score compared with placebo. They observed a positive correlation between change in BPF and time to sustained worsening of cognitive function over 2 years among placebo subjects. They saw no such correlation among natalizumab subjects.

In addition, the AFFIRM investigators also reported that there were 92% fewer gadolinium-enhancing lesions and 83% fewer new or enlarging T2-hyperintensities on magnetic resonance imaging in the natalizumab group compared with placebo.....
[Presentation title: The Effects of Natalizumab on Brain Atrophy and Cognitive Function: Results From the AFFIRM Study. Abstract P383]

New Data on TYSABRI(R) Presented at ECTRIMS Congress Demonstrate Significant Improvement in Cognitive Function in Patients with Multiple Sclerosis
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(R) (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....

New Data Presented at ECTRIMS Congress Show TYSABRI(R) Has Sustained Effect on Relapse Rate in Multiple Sclerosis Patients Treated for up to Three Years

Source: Biogen Idec and Elan Corporation,

ZUG, Switzerland and DUBLIN, Ireland--(BUSINESS WIRE)--Biogen Idec (NASDAQ: BIIB - News) and Elan Corporation, plc (NYSE: ELN - News) announced today new data that show TYSABRI® (natalizumab) has a sustained effect on relapse rate in multiple sclerosis (MS) patients treated for up to three years. These data, presented at the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Madrid, Spain, were part of long-term follow-up of TYSABRI clinical trial patients.

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. Approximately 1,900 patients and over 200 sites worldwide participated in the extension study.

Approximately 250 of these patients remained on TYSABRI monotherapy for nearly three years. The annualized relapse rate for these patients over the three-year period was 0.23, translating into an average of one relapse every 4.3 years. This was consistent with the 0.23 annualized relapse rate seen in the two-year AFFIRM study, which represented a 68% relative reduction when compared to the two-year placebo annualized relapse rate of 0.73, as published in the New England Journal of Medicine.

"Data from this long-term follow-up study show that TYSABRI has a sustained and compelling effect on relapse rates beyond two years of treatment. The efficacy benefit of TYSABRI when considered with the management of its known risks, offers an important therapeutic option for many patients living with the debilitating effects of MS," said Paul O'Connor, MD, St. Michael's Hospital, Toronto, Ontario, Canada, lead investigator of the extension study.

TYSABRI: New Pharmacoeconomic Data on TYSABRI® Demonstrate Significant Reduction in Steroid Use and Hospitalizations in Patients with Multiple Sclerosis [click for more] 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)).......

Elan Extends Tysabri's Reach to Canada [more]
...To put this in perspective, Canada has possibly the highest rate of MS in the whole world. An estimated 55,000 to 75,000 Canadians suffer from the disease -- that's nearly one-fifth the estimated number of patients in the United States.

The fortunes of Elan will rise and fall with the prospects of Tysabri. When the drug was taken off the market early last year, many investors pegged the company for bankruptcy because of its high debt load. Now that the drug has been approved for sale again in the U.S. and also for marketing in the EU, Elan has a chance to start making enough money to stem the company's losses and hopefully begin paring down some of the nearly $2 billion in debt that will be due in varying amounts in 2008 and 2011.....

TYSABRI: New Pharmacoeconomic Data on TYSABRI® Demonstrate Significant Reduction in Steroid Use and Hospitalizations in Patients with Multiple Sclerosis [click for more] 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)).......

TYSABRI: Natalizumab Has Benefits on Disability and Quality of Life in Patients With Relapsing MS: Presented at EFNS: "GLASGOW, UK -- September 11, 2006 -- Monotherapy with the alpha4 integrin antagonist natalizumab [TYSABRI] results in significant improvements in scores on health-related quality of life (QoL) questionnaires in patients with relapsing-remitting multiple sclerosis (MS), according to results of a substudy from a multicentre, randomised, double-blind, placebo-controlled, phase 3 clinical trial.

The findings were presented here on September 5th at the 10th Congress of the European Federation of Neurological Societies (EFNS) by Michael Hutchinson, MD, professor of neurology, department of neurology, St. Vincent's University Hospital, Dublin, Ireland, on behalf of the AFFIRM study investigators....."

Mayo Clinic Rochester
Dr. Claudia F. Lucchinetti,

Neurology, Mayo Clinic,

Rochester, Minn.

"The Food and Drug Administration recently reapproved Tysabri, a drug that earlier was said to be a big advance in the treatment of multiple sclerosis but caused a few instances of deadly side effects. Now that this medication is back on the market, what difference will it make in how MS patients are treated? And is it really safe?

Tysabri (brand name for natalizumab) will not make a big difference for most MS patients - at least, not right away - because the FDA reapproval carries a variety of restrictions. And the drug's link to that deadly side effect, a rare brain infection called progressive multifocal leukoencephalopathy, means that physicians will likely consider Tysabri mainly for aggressive or unresponsive cases.

In MS patients with frequent and severe flare-ups whose condition is rapidly deteriorating or for those who cannot tolerate or are not helped by other available drugs, Tysabri's benefits may well offset its one-in-a-thousand risk (based on present data) of PML.

The good news is that the FDA's TOUCH Prescribing Program - which specifies limited access to Tysabri and frequent follow-up - is essentially a long-term clinical trial that could have a big impact on the overall understanding of MS and its future treatment.

MS is a chronic disease that affects the central nervous system. In patients with MS, the body incorrectly directs immune cells against the myelin sheath that surrounds the nerves. These attacks cause inflammation and injury to the sheath and eventually to the nerves, resulting in multiple areas of scarring (sclerosis). Such damage can slow or block nerve signals that control muscle coordination, strength, sensation and vision.

Typically, MS advances in two steps: 1) initial episodes of inflammatory demyelination associated with neurologic dysfunction, which are sometimes debilitating but usually soon subside, and 2) a subsequent slow and irreversible progression of the disease.

Scientists are still unsure whether the frequency and severity of flare-ups affect the MS patient's subsequent rate of decline. They may be unrelated; or it's possible that they are related but that available drugs have been unable to reduce inflammation enough to show benefit.

With Tysabri, the research community finally has an opportunity to determine whether limiting inflammation early will slow the disease's progression. This is because the drug has reduced flare-ups by about two-thirds, and 96 percent of patients treated with Tysabri showed no new active lesions on brain imaging. If preventing early inflammation does indeed slow progression, Tysabri may be able to prove it. And if that is the case, this new approach to treating MS - whether with Tysabri itself or a safer successor - could make a substantial difference in the prognosis of many MS patients.

Tysabri's effectiveness appears to rest on its unique mode of action. Current treatments attempt to limit damage caused by inflammatory immune-system agents (called T-lymphocytes) that have already crossed the blood-brain barrier and entered the central nervous system. But Tysabri - the first MS drug that is a monoclonal antibody - prevents the T-lymphocytes from penetrating the nervous system in the first place.

It was Tysabri's remarkable performance that prompted the FDA to quickly approve its use in 2004, subject to continuing trials by the manufacturer. When those trials yielded three cases of PML (in about 3,000 patients) a year later, the company and the agency agreed to withdraw it. But regulators decided that the potential for Tysabri to prevent neurologic worsening in certain MS patients outweighed its small but serious risk and prompted the FDA to reapprove Tysabri for use and continued study earlier this year"

TYSABRI 'watched like a hawk': Angelia McCoy hopes she can feel like 'Wonder Woman' again as a test subject.
"Angelia McCoy waits for registered nurse Judi Greene to administer an infusion of Tysabri, a drug for multiple sclerosis recently re-released after its manufacturer pulled it off the market 1 1/2 years ago amid safety concerns....

Earlier this summer, federal regulators approved the company's plan to reintroduce Tysabri under strict limits. The rules say that it can only be used for people whose multiple sclerosis can't be controlled with other drugs. Also, patients may not take other medications while they are on Tysabri.Before each monthly treatment, they must fill out four surveys that track how they are faring physically and mentally. 'Do you have difficulty understanding what others are saying, or expressing yourself?' one survey asks. 'Do you have any weakness or numbness in your legs?'Each survey must be faxed to the drug manufacturer. A 'yes' answer to any of the questions would lead to an interruption in treatment while doctors check the patient for complications.The drug costs about $25,000 per year, but McCoy's is covered by the manufacturer because she is taking part in......

VIDEO: Heather Smith talks abot Tysabri
Heather Smith lives life at a relatively slow pace.

Diagnosed in 1998 with Multiple Sclerosis, she quickly became disabled.

The disease often makes her choose between herself and her 2-year-old son.

“I was at a point that I had a to pick, okay, I’m I going to take a shower or should I hang out and play with Ezra this morning,” said Smith.

Heather became desperate for life, desperate for a cure.

Eventually, she tried the drug Tysabri and noticed a miracle after only two doses.

Heather went from wheelchairs and a walker, to standing on her own with a cane.

“After being on this drug, my energy went back up and I was able to say 'gosh, I can take a shower and play with Ezra today if I wanted to'. To have a moment that I was actually improving was priceless,” Heather said.....

Biogen Idec reports loss of $0.50 per share

Tysabri Recovery Plan
"As Elan finds stability, CEO Kelly Martin is "unequivocally" confident that focusing on Tysabri was the right thing to do, writes Donal Griffin.

In an interview with this magazine last year, the late Donal Geaney wouldn't comment on Elan except to say how proud he was of what it had achieved. Having just settled an unfair dismissal case with his former employers, raking up old roots didn't interest him.

Geaney had stood down from Elan three years previously, following a crash in the company's share price. The Wall Street Journal ran a front-page story in January 2002 on some of its joint venture accounting practices. With Enron and WorldCom still fresh in Wall Street minds, Elan's share price plummeted as the US Securities and Exchange Commission (SEC) began an investigation. By July, the price had fallen by 96% and Geaney and CFO Tom Lynch had resigned.

Staring at short-terms debts of $Ibn (Eur 782m), the new management hadn't much choice but to start selling off assets. It ultimately sold off about $2.56n (Eur 1.95on) worth, with the majority going to similarly-sized pharmaceutical companies. While this gave the young Irish biotech industry its start through the exodus of talent and technologies, Geaney wasn't convinced of the restructuring that took place in his absence, believing it to be panicked and a billion-dollar destruction of value.

It's been a long time coming for Elan, as it crawls its way back towards a position of profitability.

Elan is today built on Tysabri. The vast majority of its share price hinges on it, "and rightfully so," says Gorman. Meeting the press to discuss its latest results - which saw the company shave 37% of its net losses - Martin is "unequivocally" confident that they've taken the right route in concentrating on Tysabri and Alzheimer's.

"The size of opportunity from those two areas is gigantic and the competition is fierce. Part of our recovery plan was that we needed to take assets that we were not going to focus on and move them off of our plate so that we can focus on were we think, over time, we will be best in the world.

"Getting Tysabri back to where it is for MS and getting it to where it will be for Crohn's is going to have a very significant impact from a shareholder point of view over time.

"The same will be true for Alzheimer's. So, in our focus around key programmes, the recovery plan was in two parts: it was a financial necessity and it was strategic repositioning of the company. We're now positioned around neuro-degenerative and autoimmune focus. That's where all of our focus is."

The industry doesn't question the manner in which Elan flung off its extra layers. "The strategy has worked," says Ian Hunter in Goodbody. "What they've done in the restructuring is really concentrated on the autoimmune diseases and that side of things because that's all they can afford to put research into."
."

TYSABRI: 'I'm so glad I was a guinea pig for the MS wonder drug....
"IT STARTED in a laboratory in southern San Francisco in the early nineties. Paralysed laboratory mice were suddenly able to walk when given a drug. Around the same time, thousands of miles away in Dublin, 14-year-old Carol Brennan noticed something wrong with her sight.

She had blurred vision for over a month. Then she felt a numbness in her legs and arms. Her balance started to go.

'When I was 14, I was brought in to the Eye and Ear and they thought it was an inflammation of the optic nerve - which happens to people who are in their nineties, not young people,' she recalls. 'So they sent me for an MRI scan and lesions came up.

'My Dad is one of the rare people in the world who has never lied in this life. And I remember we were getting the results after the MRI. We were driving home and Dad had very tearful eyes and I asked him, "What's wrong with me?" and he said, " Nothing, nothing, you'll be grand. They have to do more tests," and I said, "Dad, you're lying".

'When we got home he was speaking to Mam and she came downstairs bawling her eyes out and I went to Dad and said, "Please tell me". They probably wouldn't have told me at such a young age but I kind of made them - I had Multiple Sclerosis.' Carol, the youngest child of six, had little idea of what this bizarresounding condition actually meant.

'I knew people who had MS but they had died quite old. I think at that stage it was just like "oh my God I'm different". And as a teenager you just want to conform.

'And then I would read up in the medical journals on MS and just think: "Oh my God". My mam worked with older people so she was very aware of MS. She was aware of the implications and the severity of it.' There were no treatments worth the name available to the 7,000 or so Irish people with MS.

'They were generally told to go home and live their life as best they could because there was nothing that could be done for them,' says the chairman of MS Ireland, Louise Wardell.

Carol was put on self-injecting drugs called interferons which had limited effect on her condition.

'When I was on the interferons I was getting night-sweats and wasn't sleeping properly,' she says. But that was not the worst of it, the greater problem was administering the doses.

'I just couldn't do it,' she says. 'I hate needles. It was more depressing than anything else. I would get up in the morning and think, "God, I have only eight hours to go and I will have to do it again".' Her fear of self-injection became so great that she had to come off interferons. The result was a string of what MS sufferers call 'relapses' - agonising episodes of dizziness, weakness and pain that can leave them unable even to pick up a pen and write.

'I was on no drugs and getting a lot of relapses,' says Carol. 'After a relapse you get all your steroids and drugs, but you are never back 100 per cent. My doctor was saying: "You have to take something".

'But it was unfair on my mother and my family to ask them to [inject me]. My mother was upset about my health like any mother would be,' she says.

Then came news which seemed, at first, like a miracle. The drug which almost a decade earlier had helped paralysed mice walk again was being put forward for its first human trial under the brand name Tysabri.

Its maker, Elan, was Ireland's biggest pharmaceutical firm and was looking for volunteers here.

Carol needed absolutely no persuasion. When offered the chance to participate in the Tysabri trial, she accepted immediately.

It meant being administered the drug via an intravenous drip once a month.

There was no more selfinjecting.

The impact on her illness, even in the trial stage, was immediate. 'With MS you never know. Everyone is affected differently. But I have a very active life. I probably wouldn't have been able to be so active without it.

I did get a lot of relapses before I started the trial and it really reduces relapses. I think by 70 per cent. So in the space of five years, normally I would have had 10 relapses but I only had three. That's brilliant,' she says.

'In relapse, my legs get weak and my walking is impaired. And I am touching walls walking down a corridor, afraid I will fall. My arms get weak and my writing gets bad. I remember years ago I lost my wallet and when I got my cards back, because my hands were so sore, I couldn't write my name on the new credit card.' In November 2004, the U.S. Food and Drug Administration approved the drug. Initial trial results were spectacular across the board.

Tysabri was shown to reduce relapses by 66 per cent and slow progression of disability by 44 per cent.

This was the silver bullet that MS sufferers had been waiting for.

But Elan was a not a firm that had enjoyed a trouble-free life. Only two years earlier, in 2002, analysts were predicting that the company would collapse, when in the fallout from the Enron scandal in the U.S., the Securities Exchange Commission launched an investigating into Elan's accounting practices. The share price collapsed.

In July 2002, with mounting fears the company would run out of cash, chief executive Donal Geaney resigned.

Geaney had joined Elan in 1987 and presided over its transition from a E1.6million company to one with a share valuation of E20billion.

ANEW CEO sold more than E1.2billion in assets to pay off debts. Geaney, the man who had made the firm and who had developed Tysabri, was broken. He died in 2005, aged just 54.

And while none of Tysabri's earlier financial woes mattered to Carol, it gave the firm a brittle reputation.

And in February 2005, with the trial still continuing, Elan announced that one fatal and one nonfatal case of a rare brain disease known as PML were found in patients given Tysabri in combination with another drug Avonex.

Elan's share price fell off a cliff again. And Carol was caught up in the maelstrom.

'It was a disaster,' she recalls. 'I was actually in the hospital that morning and one of the doctors said, "We're after getting a phone call from Elan. You have to come off Tysabri". I said, "What happened?

What's wrong with me?" And they said, "No, it's not just you, it's everyone." I asked, "Is everything ok?"

and they said, "It's grand, they have to go back to data and so on".' Then in March 2005, a second PML death was attributed to Tysabri.

With the trials suspended, Carol's symptoms returned.

'The year I was off Tysabri I was on steroids five or six times. At Christmas I was quite unwell. And I just had this massive fear that this is it.

I'm not going to get better.

'I was on steroids four times in the space of two months and I noticed I was awful tired. My legs were weak.

My walking was terrible. My balance was terrible. I was put on steroids and they weren't working and I was pushing the doctors for more. My brother is a pharmacist and he was telling me you are only supposed to be on these steroids three times in your life - and I have been on them 15 times. They damage your whole immune system and the next time you take them they won't be as effective.' Carol's personal life was also in turmoil.

'I was going out with a guy for ages but we broke up three months before Christmas last year. I was going out with him for a year which is a long time for me! I knew before we broke up I was going to get sick, so the relapses weren't because of the break-up.

'Although stress wouldn't help it.

If you are really down and stuff, that doesn't help.' Meanwhile, Elan's share price continued to fall. It became a worldwide news story.

Carol recalls the horror of watching the TV news: 'I am doing this interview because I want people to be more aware of what Tysabri is.

When I was looking at the Elan shares dropping and on TV they had pictures of tablets and Tysabri is not even a tablet. And all the focus was on the shares. But I was thinking "but what about the people who are actually on it?"

'It was horrible to think that it was all to do with money. It was just typical of our society - it wasn't about the dampener for people who had MS, it was about money.

People like me who had been on the trial, their lives were on hold.

And it was such a disaster.

'You know people were tracking the thing though trials and all the hopes and the feeling that it would be the best thing ever and then it was nothing, full stop. Finished.

'I wouldn't have gone back to injecting myself. I probably would have stayed taking nothing. I just hate needles.

'I think from the day I was diagnosed I wanted something like Tysabri that I wouldn't have to inject myself.' Carol believes the PML cases were over-hyped: 'All the focus in the media was on the rare examples of people getting PML and not on the positives. I think if you ask anyone with MS if they are prepared to take the risk they will say "of course".' Carol thought of all the sacrifices she had made just to take part in the trials. It had meant leaving the job she was in.

'I worked in insurance for years, but they were very discriminating when I started the trials. My boss told me I would have to take an annual leave day each month so I just got fed up with that.' THE effect on her emotionally was also harrowing. 'The year off Tysabri was weird. I was reading up on stem cell therapy and things. Then I was thinking because I love kids, maybe I should think about having kids now.

'Tysabri was never tried on pregnant women so you would never know what effect it would have on kids in the long term. You wouldn't do it to another human being. So then I thought "no I don't want kids yet".

'And then I thought "well it's a year of my life, just live it" because my life had been on hold for so long.

'So I travelled to Asia and Thailand-and Australia. But I was still thinking if Tysabri comes back again I will need to be back for the trial.' Aware of the effect its suspension was having on MS sufferers, the FDA (and its EU counterpart) fasttracked Tysabri back to market as fast as they felt able to.

Finally, in June this year, came the news Carol had been praying for. The drug was re-approved, with certain restrictions.

Carol is back on Tysabri. The only MS symptoms she has now are a numbness in parts of her legs and some problems with balance.

She is delighted other MS sufferers may get their chance to take it.

'You just wish for a drug like this.

It's not a cure, but it's the nearest thing to it.' She has a new boyfriend and the future is looking bright.

'I broke it to him [about MS] the first night I met him because his sister knew me and she knew.

When I'm seeing someone I would rather they hear it from me. He was a real funny chap. He still is. He makes me laugh.' She thinks about the future and having children. 'I know I'd have to come off Tysabri. And I do want to have kids in the next few years. A lot of women with MS are in remission while they're pregnant and then when they have the kid they go into relapse.

'That's scary......"

PDL Just Got Riskier
"Tysabri was taken off the market in 2005 after it was linked to a potentially deadly infection of the brain called PML, but it was recently reapproved.

Most observers in the medical industry expect the reintroduction of Tysabri to progress slowly at first, but, considering the superior efficacy of the drug, if no more cases of PML are reported it could eventually become the blockbuster that was originally envisioned. PDL is certainly hoping for that scenario, considering it receives royalty payments on Tysabri......"

ABC News - Ex-Biogen Exec. Settles Insider Trade Case:
" A former executive at Biogen Idec Inc. who resigned last spring amid an insider trading investigation has reached a $3 million settlement with federal securities regulators.The settlement announced Thursday by the Securities and Exchange Commission requires Thomas J. Bucknum to give up $1.9 million in profit plus pay a penalty of $969,000 and $102,000 in interest. Bucknum also is barred from serving as a director or officer of a publicly traded company for five years."

TYSABRI: ELAN-BIOGEN LETTER TO DOCTORS...

"July 2006
IMPORTANT DRUG WARNING

Dear Healthcare Professional:

Biogen Idec and Elan are writing to inform you of important safety information reflected
in recent changes to the labeling for TYSABRI® (natalizumab) as it becomes available
as monotherapy for patients with relapsing forms of MS. The changes describe the risk
of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of
the brain that usually leads to death or severe disability.

Two cases of PML were observed in 1869 patients with multiple sclerosis treated for a
median of 120 weeks. A third case occurred among 1043 patients with Crohn’s disease
after the patient received 8 doses. The absolute risk for PML in patients treated with
TYSABRI® cannot be precisely estimated, and factors that might increase an individual
patient’s risk for PML have not been identified. Due to this risk, TYSABRI® is approved
only under a restricted distribution program, called the TOUCHTM Prescribing Program.
In addition, a Medication Guide has been approved by the Food and Drug
Administration and a copy of the Medication Guide is required to be given to patients
prior to TYSABRI® being administered.

The following BOXED WARNING has been added to the Prescribing Information:

WARNING
TYSABRI® increases the risk of progressive multifocal leukoencephalopathy (PML), an
opportunistic viral infection of the brain that usually leads to death or severe disability.
Although the cases of PML were limited to patients with recent or concomitant exposure
to immunomodulators or immunosuppressants, there were too few cases to rule out the
possibility that PML may occur with TYSABRI® monotherapy.

• Because of the risk of PML, TYSABRI® is available only through a special
restricted distribution program called the TOUCHTM Prescribing Program. Under
the TOUCHTM Prescribing Program, only prescribers, infusion centers, and
pharmacies associated with infusion centers registered with the program are able
to prescribe, distribute, or infuse the product. In addition, TYSABRI® must be
administered only to patients who are enrolled in and meet all the conditions of
the TOUCHTM Prescribing Program (see WARNINGS, Progressive Multifocal
Leukoencephalopathy; and WARNINGS, Prescribing, Distribution, and
Administration Program for TYSABRI®).

• Healthcare professionals should monitor patients on TYSABRI® for any new sign
or symptom that may be suggestive of PML. TYSABRI® dosing should be
withheld immediately at the first sign or symptom suggestive of PML. For diagnosis,
an evaluation that includes a gadolinium-enhanced magnetic resonance imaging
(MRI) scan of the brain and, when indicated, cerebrospinal fluid analysis for JC viral
DNA are recommended (see CONTRAINDICATIONS and WARNINGS,
Progressive Multifocal Leukoencephalopathy).


In addition, the updated Prescribing Information includes the 2-year results of the
TYSABRI® clinical trial program. Labeling changes have been made in the CLINICAL
STUDIES, INDICATIONS AND USAGE, CONTRAINDICATIONS, WARNINGS,
PRECAUTIONS, and ADVERSE REACTIONS sections of the package insert.

Prescribers should be aware that the immune system effects of TYSABRI® may
increase the risk for infections. Concurrent use of antineoplastic, immunosuppressant,
or immunomodulating agents may further increase the risk of infections, including PML
and other opportunistic infections, over the risk observed with use of TYSABRI® alone.
The safety and efficacy of TYSABRI® in combination with antineoplastic,
immunosuppressant, or immunomodulating agents have not been established.

We would also like to remind you that TYSABRI® has been associated with hypersensitivity
reactions, including serious systemic reactions (e.g., anaphylaxis) which occurred at an
incidence of <1%.>
TYSABRI® and initiate appropriate therapy. Patients who experience a hypersensitivity
reaction should not be re-treated with TYSABRI®.

TYSABRI® is indicated as monotherapy for the treatment of patients with relapsing forms of
multiple sclerosis to delay the accumulation of physical disability and reduce the
frequency of clinical exacerbations. The safety and efficacy of TYSABRI® beyond two
years are unknown. Because TYSABRI® increases the risk of PML, TYSABRI® is
generally recommended for patients who have had an inadequate response to, or are
unable to tolerate, alternate multiple sclerosis therapies.

The CLINICAL STUDIES section of the prescribing information was revised based on
the 2-year results of the TYSABRI® clinical trial program in multiple sclerosis. In the
monotherapy study, TYSABRI® (n=627) was shown to reduce the relative risk of
sustained increase in disability by 42%, compared with placebo (n=315). Seventeen
percent of TYSABRI®-treated patients demonstrated sustained increase in disability as
compared with 29% of placebo-treated patients. In this study, TYSABRI® also caused
a relative reduction in the annualized relapse rate of 67% to a rate of 0.22 as compared
with a rate of 0.67 in the placebo-treated patients.

The TOUCHTM Prescribing Program has been developed in consultation with the FDA.
This program represents our commitment to the responsible use of TYSABRI®. The
TOUCHTM program seeks to achieve the following:
• Physicians and patients are fully informed about the benefits and risks of TYSABRI®
before initiating and while on therapy
• Only appropriate patients are prescribed and infused with TYSABRI®
• Only authorized sites infuse TYSABRI®
• All TYSABRI® prescribing physicians and patients are enrolled into the TYSABRI®
registry

Biogen Idec and Elan will continue to provide a range of information and services,
including reimbursement research, infusion referral assistance, and infusion center and
patient materials.

Healthcare professionals should report any serious adverse events possibly associated
with the use of TYSABRI® to Biogen Idec at 1-800-456-2255. This information may also
be reported to FDA’s MedWatch reporting system by phone (1-800-FDA-1088), FAX (1-
800-FDA-0178), via the MedWatch website at www.fda.gov/medwatch, or by mail (using
postage paid form) to MedWatch, HF-2, 5600 Fishers Lane, Rockville, MD 20852-9787.
Health professionals and consumers should use this form for adverse event/product
problem reporting.

The revised full Prescribing Information and Medication Guide for patients are enclosed.
Should you have questions regarding the use of TYSABRI® or wish to learn more about
the TOUCHTM Prescribing Program for TYSABRI®, call 1-800-456-2255.

Sincerely,

Alfred Sandrock, MD Gordon Francis, MD
Senior Vice President, Vice President,
Neurology Research and Development Global Clinical Development
Biogen Idec Inc. Elan Pharmaceuticals, Inc.

Lauren Hoffman is Waiting on Tysabri: MS patients line up as the drug returns to market
"It's the best thing that has come along for a long time," Hoffman said. "It keeps me from getting worse."

On Monday, Hoffman received an e-mail message saying that Tysabri is on its way to the only approved distributor and 12 specialty pharmacies allowed to sell it. That means Hoffman could get a Tysabri infusion at her physician's office within five to 10 weeks.

The possible risks and side effects spelled out in the Biogen e-mail gave her some pause, Hoffman said. "But I still want to get back on it," she said.

Tysabri works by stopping infection-fighting T-cells from entering the brain, where they can cause the inflammation and scarring that progressively reduce MS patients' mobility and muscle control.

No other available MS treatment works as well, analysts and physicians say.

But its potency comes at a price: T-cells are an important part of the immune system. By interfering with them, Tysabri makes MS patients vulnerable to herpes infections and PML, a viral infection that typically leads to death or severe disability. Biogen also acknowledged that patients receiving Tysabri have come down with other atypical infections.

The possible side effects pose a dilemma for physicians.

"Everybody is excited, but also a little concerned," said Dr. Mitch Freedman of Raleigh Neurology. The practice treats about 2,000 MS patients.

Hoffman is among about a dozen patients Freedman plans to put back on Tysabri. That's a fraction of the 100 patients who were lined up for a prescription 18 months ago, Freedman said.

Dr. Ugo Goetzel of Millennium Neurology in Durham has whittled the number of patients who will receive Tysabri to a handful.

Both physicians agreed it is wise to limit the drug to patients who cannot tolerate other MS treatments or whose symptoms have gotten worse despite treatment with other drugs.

Hoffman went back on Avonex, another Biogen MS drug, when Tysabri was pulled. But Avonex made her very tired and gave her flu-like aches and pains the day after each weekly injection, she said.

The conditions that Biogen, Elan and regulators agreed on to bring Tysabri back are extensive. They include close patient monitoring for signs of PML. Physician offices must receive training before they can prescribe and administer Tysabri infusions. Prescription refills must be authorized by Biogen every six months. Also, Tysabri should not be given to patients with weakened immune systems.

Despite the safeguards, Freedman and Goetzel said they remain uneasy about Tysabri. They said they will feel better once more data on Tysabri is available from the monitoring program.......[click blue link above for full article]"

News Release: BIOGEN IDEC AND ELAN ANNOUNCE AVAILABILITY OF TYSABRI® FOR THE TREATMENT OF RELAPSING FORMS OF MS
"Cambridge, MA and Dublin, Ireland - July 24, 2006 - Biogen Idec (NASDAQ: BIIB) and Elan Corporation, plc (NYSE: ELN) today announced the commercial availability of TYSABRI® (natalizumab) for the treatment of relapsing forms of multiple sclerosis (MS) in the U.S. As previously announced, the U.S. Food and Drug Administration (FDA) approved the supplemental Biologics License Application (sBLA) for the reintroduction of TYSABRI as a monotherapy treatment for relapsing forms of MS to slow the progression of disability and reduce the frequency of clinical relapses.

The FDA granted approval for reintroduction based on the review of TYSABRI clinical trial data; revised labeling with enhanced safety warnings; and a risk management plan (TOUCH Prescribing Program) designed to inform physicians and patients of the benefits and risks of TYSABRI treatment and minimize potential risk of progressive multifocal leukoencephalopathy (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.

Under the TOUCH Prescribing Program, only prescribers, infusion centers and pharmacies associated with infusion centers registered in the TOUCH program are able to prescribe, infuse or distribute TYSABRI. Elan has contracted with a single distributor, ICS, a division of AmerisourceBergen Specialty Group, and 12 specialty pharmacies: Caremark, CuraScript, PharmaCare, PrecisionRx Specialty Solutions, Medmark, BioScrip, McKesson Specialty, Option Care, Cigna Tel-Drug Specialty Pharmacy, Aetna Specialty Pharmacy, Prescription Solutions, and Accredo NovaFactor. ICS and the 12 specialty pharmacies have been trained on the TOUCH Prescribing Program and are obligated to follow the requirements of the program in order to purchase and distribute TYSABRI to authorized infusion sites and central pharmacies.

In addition, following the recent approval by the European Commission, the companies have introduced TYSABRI in several countries in Europe.

About TYSABRI
Two-year data from the AFFIRM monotherapy trial showed that treatment with TYSABRI reduced the risk of disability progression by 42% (p<0.001),>

TYSABRI increases the risk of PML, an opportunistic viral infection of the brain that usually leads to death or severe disability. Three cases of PML occurred in clinical trial patients who were concomitantly exposed to immunomodulators (interferon beta in the patients with MS) or were immunocompromised due to recent treatment with immunosuppressants (e.g., azathioprine in the patient with Crohn's disease). Two of the cases were observed in 1,869 patients with MS treated for a median of 120 weeks. A third case of PML occurred among 1,043 patients with Crohn's disease after the patient received eight doses. The number of cases is too few and the number of patients treated too small to reliably conclude that the risk of PML is lower in patients treated with TYSABRI alone than in patients who are receiving other drugs that decrease immune function or who are otherwise immunocompromised. Healthcare professionals should monitor patients on TYSABRI for any new signs or symptoms that may be suggestive of PML. TYSABRI dosing should be withheld immediately at the first sign or symptom suggestive of PML.

TYSABRI is contraindicated in patients who have or have had PML or with known hypersensitivity to TYSABRI or any of its components. In Phase III placebo-controlled trials of TYSABRI in MS, the overall incidence and rate of other infections were balanced between TYSABRI-treated patients and controls. Herpes infections were slightly more common in patients treated with TYSABRI. Commonly reported infections with TYSABRI included urinary tract infections, lower respiratory tract infections, gastroenteritis and vaginitis. Serious opportunistic and other atypical infections have been observed in TYSABRI-treated patients, some of these patients were receiving concurrent immunosuppressants.

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 (e.g., anaphylaxis), depression and gallstones. Appendicitis was more common in patients receiving TYSABRI with AVONEX. Common adverse events reported in TYSABRI-treated patients include infusion reactions, headache, fatigue, joint and limb pain, abdominal discomfort, diarrhea and rash.

For more information about TYSABRI please visit www.biogenidec.com, www.elan.com, or www.tysabri.com...."

Tysabri Won't Top Current Drugs
"The Food and Drug Administration's approval of Biogen Idec's multiple-sclerosis treatment Tysabri to return to the market is a positive for the company, but analysts said the drug won't replace the current therapies for the disorder...."

...how many patients will use Tysabri?
: "In the case of Elan (ELN, now that the Food and Drug Administration has re-approved its multiple sclerosis drug, Tysabri, the issue is: how many patients will use Tysabri?

Our community-based research has shown that for most multiple-sclerosis patients, the current drugs (all of them blockbusters) have undesirable side effects or just don't work. Tysabri has had such miraculous results that MS patients are willing to give up all other drugs to be first in line to receive treatments when Tysabri returns to the market in July.

Our research convinces me that Tysabri will be a multibillion-dollar drug -- and interest rates, the price of oil, and the election will not affect an MS patient's decision to use Tysabri. So when Wall Street panics, as it did in January when ELN dropped 22% in two days or in June when ELN dropped 24% in two days, that's the time to buy a stock that can double over the next couple of years...."

"Elan slips despite boost from Brussels": "Elan slips despite boost from Brussels
"ELAN was one of the few losers on the Dublin market yesterday as most shares piled on new gains.The drug company saw its market price drop 52c to 1273, despite getting approval from the EU to launch its multiple sclerosis drug Tysabri on the European market.'I think people were expecting the approval to come through, which is why it didn't make a dramatic impact,' explained analyst Ian Hunter of Goodbody Stockbrokers.'Also, now that it is through, people are beginning to realise that other elements such as its pricing in Europe and its rollout in the U.S. are still to come,' he added..............."

OXiGENE'S Board of Directors Names Experienced Biotech Executive, Richard Chin, M.D., as President and Chief Executive Officer:
"Dr. Chin, SVP of Global Development at Elan Corporation and Former Head of Clinical Research for the Biotherapeutics Unit at Genentech, Tapped to Lead OXiGENE Through Its Next Stage of Corporate Growth........"

"Biogen Idec Inc. and Elan Corp.'s recalled multiple sclerosis drug Tysabri won approval by European regulators for patients with the severest cases of the disease.
...more:
"The European Commission said the drug can also be used by those who haven't been helped by older treatments, the companies said yesterday. The medicine will enter the German and Irish markets by next month.............

``The speed to market and lack of requirement for a mandatory registry as part of the risk-management plan are more positive than expected," Goodbody Stockbrokers analyst Ian Hunter said in a note yesterday.

Biogen shares rose $1.99, or 4.4 percent, to $46.97 in Nasdaq Stock Market composite trading. Elan's American depositary receipts, each representing one ordinary share, rose 16 cents to $16.49 in New York Stock Exchange composite trading.
MS is a neurological disorder that erodes muscle coordination and balance, leading to paralysis and impaired vision in some patients. The US Food and Drug Administration approved the product's return this month.

An EU panel had recommended that Tysabri be approved for patients not helped by treatment with beta-interferon drugs, such as Biogen's Avonex or Serono SA's Rebif, or for patients with rapidly progressing severe disease.

Tysabri will be the most expensive multiple sclerosis treatment on the market. Elan will raise Tysabri's price 21 percent, with a vial of the medicine costing $2,185 in the United States, Elizabeth Headon, an outside spokeswoman for Elan said June 9.

Tysabri, which is administered 13 times a year, will cost $28,400 a year for each patient, up from $23,500 previously. Analysts including Orla Hartford at NCB had forecast that the price of the drug would rise by about 10 percent after the companies spent more to study its effects over two years.

The drug will probably reach $2 billion in annual sales, Hartford said."

"Tysabri Triumphs"
".....In two separate clinical trials at Stony Brook University Hospital in 2003, about 15 to 20 patients were treated with the drug. Researchers were encouraged by the results.

"The drug was very well-tolerated," says Stony Brook neurologist Dr. Patricia K. Coyle. "And the patients did very well."..."One patient, 48-year-old James Blog of Huntington, was in the process of receiving the drug when it was pulled off shelves in February 2004. Blog, a New York City accountant, has had a mild case of MS for 15 years.

Blog began taking Tysabri in October 2003 as dual therapy with Avonex, another MS drug. He was a part of the clinical trial at Stony Brook Hospital and felt the treatment was effective.

"I was feeling good," he says.

While Blog's diagnosis may not be as serious, he sometimes experiences relapses which cause disorientation, stiff legs and a lack of coordination. During his last episode, which happened six months after discontinuing Tysabri and Avonex, he needed steroids to help him bounce back.

The decision to take or switch to Tysabri hinges on the opinion of the patient's neurologist. In July, Blog will be meeting with his neurologist at Stony Brook to determine if his future will include Tysabri. Speaking from experience, he hopes he's a candidate.

"It works great," Blog says. "But in three weeks, I'll know if I can get back on it. I would trust my doctor."

UK Multiple Sclerosis Society News Release - Tysabri approved: "Tysabri has been licensed for use in the UK today. The drug still needs to be reviewed by NICE and we await to hear as to whether NICE will %u201Cfast-track%u201D the appraisal through the new Single Technology Assessment of sixteen weeks, or whether it will go through the longer main stream appraisal which would not complete until October 2007.....MORE"

"What ails Teva?"...more:
"...The second factor is related to Teva's ethical multiple sclerosis drug, Copaxone, which breaks new sales records every quarter. Many analysts believe that Teva's ability to increase Copaxone sales has peaked because of the US Food and Drug Administration (FDA) marketing approval, albeit restrictive, for Tysabri, made by Biogen Idec Inc....."

CNS can send out signals to invite autoimmune attacks: Washington University in St.Louis - School of Medicine
"By Washington University School of Medicine in St. Louis.....

"Experiments by others suggested that {Tysabri)natalizumab prevented immune cells from crossing the blood-brain barrier — it was thought to prevent the cells from leaving the blood stream,"

It may sound like a case of blame the victim, but researchers at Washington University School of Medicine in St. Louis have shown that cells in the central nervous system can sometimes send out signals that invite hostile immune system attacks. In mice the researchers studied, this invitation resulted in damage to the protective covering of nerves, causing a disease resembling multiple sclerosis.

"It's been clear for quite a while that our own lymphocytes (white blood cells) have the ability to enter the central nervous system and react with the cells there," says John Russell, Ph.D., professor of molecular biology and pharmacology. "Under normal circumstances, the brain and the immune system cooperate to keep out those cells that might harm the brain. But in people with multiple sclerosis, they get in."

The researchers found that they could prevent destructive immune cells from entering nervous system tissue by eliminating a molecular switch that sends "come here" messages to immune cells. Ordinarily, flipping that switch would cause immune cells to rush to the vicinity of the cells that sent the signals and destroy whatever they consider a danger — including nerve cell coatings.

But in the mice in which the switch was removed, the researchers saw that immune cells previously primed by the scientists to attack the central nervous system (CNS) did not enter the CNS, and the mice stayed healthy.

In contrast, normal mice treated with the same hostile immune cells had numerous immune cells in their CNS tissue and developed symptoms similar to multiple sclerosis.

"What allows the primed lymphocytes into the CNS are signals from the CNS asking them in," Russell says. "We determined that the astrocytes, the specialized cells that provide nutrients to neurons, are among the cells most active in sending signals to attract lymphocytes."

The molecular switch that sends the call to immune cells is termed the tumor necrosis factor receptor (TNFR). When TNFR is activated, it causes cells to send out signal molecules called chemokines that direct immune cells to the site of damage or infection. The researchers found that astrocytes in mice were producing chemokines in response to activation of their TNFR molecules.

TNFR activation also makes the astrocytes bristle with specific adhesion molecules that act like Velcro to bind to similar molecules on the surface of the immune cells. That allows the immune cells that are attracted by the chemokines to stick around and do more harm.

One of the most promising new drugs for treating multiple sclerosis, natalizumab (tradename Tysabri), works by blocking the ability of the immune cells to stick in the CNS through this Velcro mechanism, Russell notes. Natalizumab is being tested in clinical trials and appears to be much better at preventing the nerve cell destruction associated with multiple sclerosis than previous therapies.

"Experiments by others suggested that natalizumab prevented immune cells from crossing the blood-brain barrier — it was thought to prevent the cells from leaving the blood stream," Russell says. "We are working on that question, and we think that it doesn't necessarily prevent them from getting out of the blood, but it does keep them from getting further into the brain. The immune cells pile up in the space around the blood vessels. This space, the perivascular space, serves as a gatekeeper to determine what gets in and what doesn't."

Next, the research team will study various regions of the brain to determine the types of signals sent to and from different areas of the CNS to the immune system.

- Gimenez MA, Sim J, Archambault AS, Klein RS, Russell JH. A tumor necrosis factor dependent receptor 1-dependent conversation between central nervous system-specific T cells and the central nervous system is required for inflammatory infiltration of the spinal cord. American Journal of Pathology 2006;168(4):1200-1209."

Dr. Timothy Vollmer, Chairman, Division of Neurology, Barrow Neurological Institute, has just informed me that BNI is now a "Tysabri Infusion Center" and that the "Details will be worked out" soon!

I will post more information on Barrow Neurological Institute's upcoming "Tysabri Infusion Center" as soon as I receive them.


Stan Swartz
CEO
MS News Channel

Free Patient Webcast on MS and the FDA's Reapproval of Tysabri June 22nd, 8:30 PM (Eastern)NurseWeek:
"Program to Feature Prominent MS Experts Discussing the Drug and What It Means for Consumers"
WHO: Howard Rossman, D.O., F.A.C.N. Dr. Rossman spearheaded the
creation of the M.I.N.D. Multiple Sclerosis Center located in
Farmingham Hills, MI and serves as Medical Director of the
Center which presently services over 1,800 patients with MS.

WHEN: Thursday, June 22nd 2006
8:30 PM (Eastern)
5:30 PM (Pacific)
WHERE: Register online at http://www.healthtalk.com/msprogram or
call 1-800-522-3254.
COST: Free

Elan: TYSABRI Information Center

"On February 28, 2005, Elan and Biogen Idec voluntarily suspended TYSABRI from the U.S. market and dosing in all ongoing clinical trials based on reports of PML. Elan and Biogen Idec completed a comprehensive safety evaluation of more than 3,000 TYSABRI patients in collaboration with leading experts in PML and MS. The results of the safety evaluation yielded no new confirmed cases of PML beyond the three previously reported.

On March 8, 2006, the Peripheral and Central Nervous System Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA) voted unanimously to recommend reintroduction of TYSABRI as a treatment for relapsing forms of MS. The companies anticipate action by the Agency regarding the reintroduction for TYSABRI in the U.S. on or before June 28, 2006. The companies' application for approval of TYSABRI as a treatment for MS is also under review with the European Medicines Agency.

On March 29, 2006, the companies announced they have enrolled and dosed the first patients in the TYSABRI monotherapy safety extension study program in MS. Patients who previously participated in the Phase III MS trials and subsequent safety evaluation are eligible to be screened for entry in this open label multi-center study. Sites throughout Europe, the United States, Canada, Australia, New Zealand and Israel are expected to enroll patients....."

Recent News
» CHMP Issues Positive Opinion for TYSABRI® as a Treatment for Relapsing-Remitting Multiple Sclerosis (4/28/06)
» New Data on TYSABRI® Demonstrate Significant Effects on Health-Related Quality of Life Measures in Patients with Multiple Sclerosis (4/6/06)
» Biogen Idec and Elan Announce Re-Initiation of TYSABRI® Clinical Trial Dosing in Multiple Sclerosis (29/3/2006)
» Biogen Idec and Elan Announce That FDA Will Extend Regulatory Review Period for the Reintroduction of TYSABRI® for Multiple Sclerosis(3/22/2006)
» FDA Advisory Committee Unanimously Recommends Reintroduction of TYSABRI® for the Treatment of Relapsing Forms of Multiple Sclerosis(3/8/2006)
» TYSABRI® Two-Year Phase III Multiple Sclerosis Clinical Trial Results and Safety Evaluation Published in New England Journal of Medicine; TYSABRI Currently Under Review with U.S. and European Regulatory Authorities(3/1/2006)
» Elan Announces the Suspension of Trading of Its Shares Commencing March 7, 2006 For Up to Two Days; Suspension of Trading Due to Two Day FDA Advisory Committee Meeting to Review Tysabri(2/28/2006)
» TYSABRI® Multiple Sclerosis Clinical Trial Hold Lifted by FDA; Biogen Idec and Elan to Resume Clinical Trial Dosing in MS(2/15/2006)
» Biogen Idec and Elan Announce Notification of FDA Advisory Committee Meeting to Review TYSABRI® for the Treatment of Multiple Sclerosis (1/23/06)
» Biogen Idec and Elan Announce FDA Acceptance of Supplemental Biologics License Application and Priority Review Designation for TYSABRI® in Multiple Sclerosis(11/17/05)
» Elan and Biogen Idec Announce TYSABRI® Safety Evaluation Findings in Crohn's Disease and Rheumatoid /Arthritis Patients; TYSABRI Safety Evaluation Complete; No New Confirmed Cases of PML (10/17/05)
» Biogen Idec and Elan Submit Supplemental Biologics License Application to the FDA for TYSABRI® in Multiple Sclerosis(9/26/05)
» Elan and Biogen Idec Provide an Update on TYSABRI® (9/20/05)
» Biogen Idec and Elan Announce TYSABRI® Safety Evaluation Update (8/9/05)
» Two-Year SENTINEL Data Evaluating TYSABRI® in Addition to AVONEX® Reinforce Efficacy in Multiple Sclerosis (7/18/05)
» TYSABRI® Phase III Induction Trial in Crohn's Disease Meets Primary Endpoint; TYSABRI Induced Statistically Significant Response and Remission in Patients with Active Disease (6/30/05)
» Positive One-Year Data From SENTINEL Trial Evaluating Addition of TYSABRI® to AVONEX® Presented at American Academy of Neurology Meeting;Data from GLANCE Safety Study Also Presented (4/13/05)
» TYSABRI® Two-Year Monotherapy Data Support Positive One-Year Efficacy Findings and Show Significant Reduction in Risk of Disability Progression (4/12/05)
» Elan and Biogen Idec Announce TYSABRI® Update (3/30/05)
» Biogen Idec and Elan Announce Update on TYSABRI® 3/3/05
» Biogen Idec and Elan Announce Voluntary Suspension of TYSABRI®

FDA INFO CENTER ON TYSABRI:

CLICK HERE TO GO TO THE U.S. FOOD AND DRUG ADMINISTRATION

"Elan Raises Tysabri Price as Drug Returns to Market (Update2) June 9 (Bloomberg): -- Elan Corp. will raise the price of
its multiple sclerosis treatment Tysabri by 21 percent when the
drug returns to pharmacy shelves next month.

The medicine will cost $2,185 a vial in the U.S., according
to Elizabeth Headon, an outside spokeswoman for Dublin-based
Elan. The U.S. Food and Drug Administration gave Elan and
partner Biogen Idec Inc. permission to re-introduce the
treatment this week.

Tysabri, which is administered 13 times a year, will cost
$28,400 a year per patient, up from $23,500 previously. Analysts
including Orla Hartford at NCB had forecast that the price of
the drug, which was withdrawn last year after links to a deadly
infection, would rise by about 10 percent after the companies
spent more to study its effects over two years.

``This is $4,900 ahead of the $23,500 we have built into
our numbers,'' Ian Hunter, analyst at Goodbody's in Dublin, said
in a note to clients. It ``gives us further comfort in our
numbers and we believe will act as a support of the share price
at current levels.''

Elan shares fell 30 cents, or 2.4 percent, to 12.05 euros
at 10:50 a.m. in Dublin. They've gained 7 percent this year.
Hartford of NCB raised her U.S. peak revenue estimates for
Tysabri to $1.33 billion from $1.10 billion in 2010. She left
her European sales estimates unchanged.

Rebif, Betaseron
``This is a major topic for us,'' Elan Chief Executive
Officer Kelly Martin said on May 25, describing pricing
discussions with Biogen. ``The whole market has moved up by 20
to 30 percent.''
Serono SA's Rebif costs $22,875 for a year, while Schering
AG's Betaseron costs $19,289 and Biogen's older Avonex costs
$19,008, according to documents on the National MS Society's Web
site. The figures are the average annual wholesale prices for
the recommended dosage. Actual cost may vary, the group said."

Elan: TYSABRI NEWS RELEASE: Pricing

"TYSABRI® (natalizumab) will be available upon the completion of key activities related to the risk management plan, including finalization of educational and training materials, internal validation of systems based on final FDA requirements and training of internal personnel. As such, Elan and Biogen Idec anticipate TYSABRI will be available in July.

The wholesale acquisition cost is $2184.62 per vial.

Elan and Biogen Idec are committed to making TYSABRI accessible to appropriate patients who may benefit from therapy. To achieve this goal, programs have been developed to assist patients who are uninsured or who require financial assistance. Patients who require financial assistance can receive more information by calling MS ActiveSource at 1-800-456-2255. "

Elan's sets Tysabri pricing 22% above market forecasts: the wholesale cost per annum of a patient's treatment would now be $28,400
: "Irish drug company Elan Corp. (ELN) said Friday its multiple sclerosis drug Tysabri will have a wholesale price of $2,185 per 15-milliliter vial, which analysts say is nearly 21% above expectations.

The company has revised its pricing in line with that of MS treatments in general, which have risen in price between 10% and 27% since November 2004, a company spokeswoman told Dow Jones Newswires. .....the wholesale cost per annum of a patient's treatment would now be $28,400"

Biogen Idec - TYSABRI (natalizumab) Information Center

TYSABRI -A LETTER FROM BIOGEN IDEC - "To the MS Community"::

"On June 5, 2006, Biogen Idec and Elan announced that the FDA approved a supplemental Biologics License Application (sBLA) for the reintroduction of TYSABRI (natalizumab) as a monotherapy treatment for relapsing forms of multiple sclerosis (MS) to slow the progression of disability and reduce the frequency of clinical relapses. This is an important step forward for people with MS, and we believe TYSABRI offers new hope for those living with this devastating disease.
TYSABRI has demonstrated very promising benefits in patients with relapsing forms of MS. It is the reason why we have worked so diligently to make this product available again to the MS community. At the same time, it is critical that patients and physicians understand the risks of TYSABRI treatment, including the risk of PML. Ultimately, the decision to start TYSABRI will be based on an individual patient's condition and a discussion between physicians and patients of the benefits and risks. Because of these risks, TYSABRI is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, alternate multiple sclerosis therapies.....[CLICK ABOVE FOR MORE]"

For information about the FDA approval, go to the FDA's Web site - CLICK HERE

FDA allows MS drug Tysabri back on market. - Jun. 5, 2006: CNN MONEY

"U.S. health officials cleared the way Monday for multiple sclerosis drug Tysabri to return to the market with restrictions, following its withdrawal last year when it was linked to a rare but potentially fatal brain disease."

"Three patients taking the drug, made by Biogen Idec Inc (Research). and distributed by Elan Corp. (Research), had developed progressive multifocal leukoencephalopathy. Two of them died.

Under the Food and Drug Administration-approved plan, doctors, infusion centers and pharmacies must register with the companies before prescribing Tysabri. Patients must also enroll.

As another safeguard, patients must receive an MRI, or magnetic resonance imaging, scan before treatment to help differentiate MS symptoms from those linked to the brain disease, the FDA said.

Tysabri should be used as a stand-alone treatment and not with other drugs that suppress the immune system, the agency added. It also should be used in patients who have not responded adequately to, or cannot tolerate, other MS treatments.

According to the National Institutes of Health, about 250,000 to 350,000 Americans have been diagnosed with MS, a disease of the central nervous system with no known cure.

Patients with the degenerative disease face attacks on their nerve tissue by their immune system, initially causing blurred vision and leading to muscle weakness and memory problems, among other symptoms.

Tysabri had been on track to be a potential billion-dollar-a-year seller before the withdrawal, and is seen as key to helping Elan recover from a brush with bankruptcy in 2000

Still, shares of both companies were lower in afternoon trading Monday. Elan shares were down 13 percent, or $2.46, at 16.52 in late afternoon trading on the New York Stock Exchange, while Biogen was off 4.86 percent, or $2.32, at $45.39 on Nasdaq.

Both companies said renewed sales of the drug would give MS patients another option to treat their debilitating disease.

'There continues to be a significant unmet medical need where Tysabri will be an important treatment option,' Elan Chief Executive Officer Kelly Martin said in a statement.

Elan has said it hopes to relaunch the drug in the third quarter and may raise its price, citing increases for rival MS therapies.

Lehman Brothers analysts have said Tysabri could win 10 percent of the market from competitor Serono's Rebif within two years.

Other MS treatments include Serono and OSI Pharmaceutical Inc's Novantrone, Biogen's Avonex, Schering AG's Betaseron, and Teva Pharmaceutical Inc's Copaxone."

FDA NEWS RELEASE ON TYSABRI: CICK TO GO TO FDA WEBSITE

Elan, Biogen slide on Tysabri news :
"Shares of partners Elan and Biogen Idec slid on Monday after they announced that while the Food and Drug Administration has ruled to allow its recalled multiple sclerosis drug Tysabri back on the market, the drug's use will be significantly restricted."

Breaking News - FDA Approves Resumed Marketing of Tysabri (Natalizumab) Under Special Distribution Program
"The Food and Drug Administration (FDA) today approved an application for resumed marketing of Tysabri (natalizumab) subject to a special restricted distribution program.

Tysabri is a monoclonal antibody used to treat patients with relapsing forms of multiple sclerosis (MS) to reduce the frequency of exacerbations (flare-ups).

Tysabri is indicated for use as a monotherapy, meaning it should not be used in combination with other immune system modifying drugs, and is for patients who have not responded adequately to, or cannot tolerate, other treatments for MS.

Tysabri was initially approved by the FDA in November 2004, but was withdrawn by the manufacturer, Biogen-Idec, in February 2005, after three patients in the drug's clinical trials developed progressive multifocal leukoencephalopathy (PML), a serious and rare viral infection of the brain. Two of the cases were fatal. Based on this information, FDA put clinical trials of the drug on hold in February 2005.

FDA allowed a clinical trial of Tysabri to resume in February 2006, following a re-examination of the patients who had participated in the previous clinical trials, confirming that there were no additional cases of PML.

To decrease the possibility of patients developing PML in the future, while also making Tysabri available to appropriate MS patients, FDA consulted in March 2006 with its Peripheral and Central Nervous Systems Drugs Advisory Committee.

The Advisory Committee recommended a risk-minimization program with mandatory patient registration and periodic follow-up to identify as early as possible any cases of PML that may occur, and to try to determine the reason the infection occurs. In response, Biogen-Idec, submitted to FDA a Risk Management Plan, called the TOUCH Prescribing Program, to help ensure safe use of the product.

Following a thorough review of Biogen-Idec's Risk Management Plan and proposed changes to its original marketing application, FDA determined that Tysabri can be made available under the TOUCH Program with the following main features:

The drug will only be prescribed, distributed, and infused by prescribers, infusion centers, and pharmacies registered with the program.

Tysabri will only be administered to patients who are enrolled in the program.

Prior to initiating the therapy, health care professionals are to obtain the patient's Magnetic Resonance Imaging (MRI) scan to help differentiate potential future multiple sclerosis symptoms from PML.

Patients on Tysabri are to be evaluated at 3 and 6 months after the first infusion and every 6 months after that, and their status will be reported regularly to Biogen Idec."

Special Report: Green light for drug brings hope to Elan - UK Sunday Times :
"IN a shabby hotel in a scruffy suburb of Washington DC, Heather Smith brought a packed room full of doctors, healthcare analysts and pharmaceutical executives to the edge of tears.
The 36-year-old from Indiana, a multiple sclerosis sufferer since 1998, was one of more than 40 patients and other witnesses who had come to Gaithersburg to testify before a panel of medical experts about Tysabri, a drug pulled from the market early last year after two people died from a rare brain infection.

Like others there that day in March, Smith requested the chance to make her own judgment about the risks involved in taking the drug. But she was also motivated “by other requests that I hear every day”.

“Requests such as: ‘You dance with me, momma?’ ‘You chase me, momma?’ ‘You carry me, please?’ These requests from my son Ezra, that I cannot fulfil, are the key to my risk-benefit equation.”

Choking back her tears, Smith said that MS had meant she was unable to walk unaided. But “after only one dose I felt that Tysabri was a miracle for me. I was able to make outings on my own. My mobility drastically improved.

“The best reward was that I had more energy to spend with my son. I no longer had to choose between playing with Ezra or taking a shower. I could freely enjoy each moment of his life with a renewed hope.

“I may never be able to carry my son Ezra — or chase him or dance with him — but he deserves a Mom that is as healthy as possible. Each day without Tysabri is a day without hope.”

Smith was given the hope she sought. The advisory committee unanimously voted to recommend the reintroduction of Tysabri. The US Food and Drug Administration (FDA) is expected to ratify its decision any day, possibly as early as this week.

That decision will bring hope, not just to Heather Smith and hundreds of thousands of other MS sufferers, but also to the employees and shareholders of Elan, the Irish drug company that developed the medicine.

The reintroduction of Tysabri, when it comes, will mark the latest upward lurch in a remarkable five-year rollercoaster ride for Elan.

The company nearly went bust, clawed its way back from the brink with the help of Tysabri, but was then thrown to the floor again last year when the product was withdrawn. Can this latest recovery last? Kelly Martin certainly hopes so. Martin, a former investment banker with a liking for woollen sweaters, has nursed Elan through two crises since taking over as chief executive in early 2003. After surviving an attempted boardroom coup last year, he is confidently planning for Elan’s long-term success.

“We have come through a lot of things that most of the world thought we would never get through,” he said. “There’s nothing like multiple near-death experiences to sharpen the focus.

“We want to be one of the leading biopharmaceutical companies in the world in the areas of neurodegeneration (Alzheimer’s and Parkinson’s disease) and auto-immune disease (MS and Crohn’s disease). We want to be the largest European biotech company in the near term.”

Remarkably, after all its travails, Elan is already closing in on this first objective. After the recent run-up in its New York-traded shares, it is valued at $8 billion (£4.2 billion), only a little less than Switzerland’s Serono, another company that grew rich on the success of a multiple-sclerosis drug.

Elan has harboured big ambitions before. It was arguably Ireland’s most successful company in the 1990s, reaching a peak valuation of $25 billion as it raced through more than 20 acquisitions in five years. Along the way it took stakes in 55 biotech firms — effectively outsourcing its research and development to small, joint-venture partners.

But Ireland’s most highly valued company came crashing down — its stock falling from $65 to $1 — when it was realised these opaque joint-venture arrangements flattered profits, and were financed by vast off-balance-sheet borrowings.

Martin, an American banker who was formerly a senior trouble-shooter at Merrill Lynch, set to work to simplify the company and its balance sheet.

Elan’s 5,000 employees were spread across 35 locations, stretching from Athlone in central Ireland to San Diego. Over the course of two years, all 55 joint ventures were sold, and the cash from these and other disposals was used to pay down debt.

All the while, Martin said, Elan remained focused on helping patients with what he believes is truly innovative science. “We continued to invest in our science throughout the restructuring,” he said.

In February 2004 Elan received an unexpected boost. Preliminary results from trials of Tysabri were so “spectacular” that the FDA asked for an accelerated review. This was an indication that the world’s most important health regulator thought the drug could represent an important advance in the treatment of a debilitating disease.

MS is a disease of the central nervous system that affects more than 1m people worldwide. It can progressively cause numbness, loss of balance, disability, blindness and paralysis.

By November the FDA had approved Tysabri for the treatment of MS sufferers. Trial data suggested that the drug, taken by monthly infusion, could reduce the rate of MS relapses (or attacks) by two-thirds. Patients were eager to try the expensive drug, the first new MS treatment for a decade.

“In the first 10 weeks we had 7,000 patients on the drug,” said Martin. “We had 25,000 patients in the queue.”

With a course of treatment costing $23,500 a year, after only 10 weeks Elan and its marketing partner, Biogen, a large American biotech company, were selling a drug that was set to take $700m in its first year. From the pit of financial turmoil, Elan’s shares quadrupled during 2004.

Then, last February, disaster struck again. “It was a Friday,” Martin said. “I had just got off a plane.” The chief executive of Biogen called with news that two patients, who had been taking Tysabri in combination with Biogen’s Avonex, had died of a rare brain infection called PML — progressive multifocal leukoencephalopathy.”

PML was so rare that even many neurologists had no experience of it. “We had spent thousands of hours talking about the risk of opportunistic infections,” said Martin. “In all these discussions, PML had never come up once.”

Elan and Biogen were soon in constant dialogue with the FDA, trying to decide how best to protect patients. “We did not know why PML occurred,” said Martin. “We did not know whether (the problem was) the combination of drugs. We could not rely on neurologists because very few of them had the intelligence to be our front line of defence.”

After three days of intense discussions, Elan and Biogen pulled the drug. “We needed to protect the patients and we needed to protect the drug, because the drug was spectacular,” said Martin. Elan’s shares slumped sickeningly once more.

“The stock dropped from $27 to $3, which is an experience,” said Martin, drily. Employees who had seen their savings in Elan shares destroyed by the earlier accounting crisis were once again confronted by the loss of their dreams.

Despite the doubts of investors, Martin was sure from the outset that Tysabri could be saved. “I was confident that it would be made available again because of the efficacy of the drug and because patients were declining,” he said.

“If you know someone with MS and they’re declining, there’s nothing they can do. They’re going to have a cane, and go into a wheelchair, and eventually they stop breathing.”

Allison Hulme, head of the Tysabri business, and Ted Yednock, head of global research, set to work to understand what had gone wrong.

Independent experts reviewed the data from nearly every one of the 3,000 patients who had taken Tysabri in clinical trials — MS patients, rheumatoid arthritis patients and Crohn’s disease patients.

Over the course of four months, these patients were given MRI scans, physical examinations and lumbar punctures. To Martin’s relief, there were no other PML cases beyond the first three identified in February and March.

And Tysabri alone has not been shown to cause PML. It appears the infection was caused by an interaction with Avonex.

Based on the trial data, researchers estimate the risk of MS patients on Tysabri contracting PML is one in a 1,000 — small but real. It is this risk that Heather Smith and the other patients who spoke up for Tysabri are prepared to run in the hope of securing a better quality of life.

With its case strengthened by two-year trial data, Elan filed for approval for Tysabri once more, this time as a monotherapy. “The two-year data were better,” said Martin. Tysabri was shown to reduce the number of brain lesions caused by MS and, in many cases, to slow the disease’s progress.

“The data make it a better drug,” said Martin. “Our decision of last February which was very difficult to make is, at the end of the day, going to position Tysabri correctly from a patient-choice point of view and correctly from the long-term business point of view.”

When Tysabri returns to the market — a European approval is expected to follow shortly after the American go-ahead — new patient monitoring and other safety controls will be introduced to limit the risk of PML. The drug will also be restricted to patients with the relapsing form of MS, and not given to those with compromised immune systems.

Although this means the likely patient population shrinks, from 1m to perhaps 600,000, by the strange logic of the pharmaceutical industry, Elan could make just as much money as before.

The price of Serono’s Rebif has increased substantially over the past couple of years, and Elan hopes Tysabri will command a significant premium.

Analysts, such as Goodbody Stockbrokers, forecast peak sales of nearly $2 billion a year. This ignores the possible use of the drug in Crohn’s disease.

Ian Hunter, analyst at Goodbody, is cautious about early sales of Tysabri. Many patients will be wary after last year’s problems, and will wait to see whether there are any more cases of PML. Hunter said it was therefore unlikely Tysabri would see the explosive take-off it enjoyed in late 2004. Hunter said that if Tysabri proved to be safe when prescribed more widely, demand for the drug would quickly accelerate.

Such a blockbuster success would transform the company that developed Tysabri, but Martin said this medicine was only “the start of the Elan story.

“We think our science platform is truly unique,” he said. “We believe we can use that to have an impact on millions of patients around the world.

“If we can execute (our plans), the value of the company will take care of itself.”"

Elan says aims for clarity on Tysabri by June 28
"Speaking at the group's annual general meeting in Dublin, Chief Executive Kelly Martin said he hoped that the group would have more of an idea of the drug's future prospects by June 28."

This "Tysabri News" site is being remodeled...please pardon our construction!

Elan targets June for Tysabri future:
"Elan is hoping to clarify the future of its multiple sclerosis drug Tysabri by the end of June, it confirmed today. Speaking at the group's annual general meeting, Elan's Chief Executive Kelly Martin said he hoped that Elan would have a better idea about the controversial drug's future prospects by June 28. The company is hoping to get the goahead from regulators in June, allowing them to begin relaunching the drug in the third quarter...."

Tysabri: A RAISE IN IT'S PRICE?: "Chief Executive Kelly Martin said Thursday there is future 'headroom' to raise the price of MS drug Tysabri after its anticipated return to the market in the U.S. The U.S. Food & Drug Administration will make a final decision on Tysabri's re-entry by June 28, and most analysts see it back on the market in the U.S. inthe third quarter of 2006. 'Clearly there's headroom and a business legitimacy for one to raise the price,' Martin told a press briefing after the company's annual general meeting, adding the issue will be discussed with Elan's Tysabri partner Biogen Idec Inc...."

New Drug Therapies Look Promising for Bowel Diseases - Forbes.com:
".....Another study of Tysabri, which included 2,248 patients with either Crohn's disease, multiple sclerosis or rheumatoid
arthritis, found the risk of developing the PML brain infection wasvery low, according to Dr. William Sandborn of the Mayo Clinic, who led the study. Before the voluntary recall of the drug, threepatients were identified with the infection, and four more
infections were initially reported in post-marketing reviews. Sandborn's analysis, in which his team checked spinal fluid and
blood, found no additional cases among the patients studied, and the four post-marketing cases did not have the infection after
all......."

Doctors Seen as Key to Tysabri Success - Los Angeles Times

Pharma Companies Advised To Build Buzz Before FDA Approval - 05/03/2006

Elan's Tysabri drug recommended by E.U. committee
: "Shares in Irish biotechnology company Elan Corp. PLC (ELN) rose 4.0% Friday on news that the scientific committee of the European Medicines Agency had recommended the return to market of its key drug, multiple sclerosis treatment Tysabri.

Analysts say Tysabri's return now looks inevitable in the E.U. - albeit on a restricted basis - and in the U.S. after last month's similar ruling by the advisory committee for the U.S. Food & Drug Administration....."

MORE
Mary Carraux misses the drug she took for more than two months in an attempt to slow her multiple sclerosis.

“I felt like a million bucks on the drug; it was the best I ever felt,” said Carraux, 47. “My everyday symptoms were so much lighter.”

The Holmen, Wis., woman used Tysabri, which was withdrawn in February 2005 after only four months on the market when three people in clinical trials developed a rare disease, PML. Two died, including a person with MS.

“When I heard the drug was pulled,” Carraux said, “I knew it was going to be a bad day.”

In March, a Food and Drug Admin-istration advisory committee recommended Tysabri be approved for patients with relapsing MS — those who experience periodic flare-ups of symptoms. The FDA will consider the advisory panel’s recommendation in June.

Three years ago, Carraux, a Franciscan Skemp courier and phlebotomist, began participating in the annual MS Walk in La Crosse. That year, her team walked in heavy rain. From then on, her team name was Soggy Phlebotomists.....

MORE - The Boston Globe: "Opinion may have an effect on final decision by FDA"

MAS

The Weekly Standard:
. The issue was their access to Tysabri, a breakthrough biotech drug with a unique ability to slow down the debilitating progression so feared by MS patients. The manufacturers pulled Tysabri from the market after two patients died from an unexpected side effect. Now the FDA has to decide whether to let the drug come back after new research has verified its potency against MS while also suggesting a 1 in 1,000 chance of the fatal side effect....."

MORE
: "Biogen Idec and Elan said their multiple-sclerosis drug Tysabri has been recommended for approval in Europe.

As the companies await the drug's return to the U.S. market this year, they announced Friday that Europe's Committee for Medicinal Products for Human Use has issued an opinion that Tysabri should be approved for relapsing-remitting MS to delay the progression of disability and reduce the frequency of relapses.

The Committee stipulated that Tysabri be used as single therapy either in patients with highly active relapsing-remitting MS who have failed to respond to treatment with a beta-interferon or in patients who have rapidly evolving severe relapsing-remitting MS.

The European body relied on data from the companies' phase 3 AFFIRM monotherapy trial and the phase 3 SENTINEL trial in which TYSABRI was administered in combination with Avonex (interferon beta-1a).

The Europeans also considered a comprehensive safety analysis the drug makers conducted following reports of three cases of a deadly brain infection -- progressive multifocal leukoencephalopathy -- in patients taking Tysabri. The safety analysis turned up no further cases of PML."

MORE - New York Times
"Data presented at American Academy of Neurology Annual Meeting
also Show Impact on Measures of Visual Function and Disability
Progression

Biogen Idec (BIIB) and Elan Corporation, plc (ELN)
announced today that in Phase III multiple sclerosis (MS) studies
TYSABRI(R) (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......"

"On behalf of everyone at Biogen Idec and Elan, I want to thank the many people living with MS, their caregivers, physicians and others for expressing your thoughts and opinions on TYSABRI® (natalizumab) over the last several months. In particular, at the FDA Advisory Committee meeting in March, dozens of patients and physicians spoke eloquently about the unmet medical need in multiple sclerosis and the need for new therapeutic options like TYSABRI. It took a great deal of courage to share their voice, and in the end, it helped inform the process for reintroducing TYSABRI in the US, and also helped advance a better understanding that MS is a serious and often debilitating disease.

The unanimous recommendation from the FDA Advisory Committee was an important step forward in our efforts to bring TYSABRI back. The FDA has stated that it needs more time to review the TYSABRI Risk Management Plan, and we now expect to hear back from the Agency on or before June 28.

The Risk Management Plan (RiskMAP) is an important component of the reintroduction of TYSABRI and we want to make sure that it is implemented appropriately and is understood and operationalized by healthcare professionals and patients. The RiskMAP is designed to facilitate informed risk-benefit conversations between physicians and patients, minimize the risk of progressive multifocal leukoencephalopathy (PML) and assess the incidence and risk factors associated with TYSABRI. We continue to work diligently with the FDA to finalize the details of this.

We hope to offer people living with MS the option to choose this therapy once again. Thank you again for your patience and inspiration during this time.

Sincerely,



James C. Mullen
President and CEO
Biogen Idec"

NEW DATA ON TYSABRI® DEMONSTRATE SIGNIFICANT EFFECTS ON HEALTH-RELATED QUALITY OF LIFE MEASURES IN PATIENTS WITH MS
Biogen Idec - MORE
Data presented at American Academy of Neurology Annual Meeting also Show Impact on Measures of Visual Function and Disability Progression
"San Diego, California - April 6, 2006 - 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.

Biogen Idec and Elan had previously voluntarily suspended TYSABRI from the U.S. market and dosing in all ongoing clinical trials based on reports of PML. Biogen Idec and Elan completed a comprehensive safety evaluation of more than 3,000 TYSABRI patients in collaboration with leading experts in PML and MS. The results of the safety evaluation yielded no new confirmed cases of PML beyond the three previously reported.

On March 8, 2006, the Peripheral and Central Nervous System Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA) voted unanimously to recommend reintroduction of TYSABRI as a treatment for relapsing forms of MS. The companies anticipate action by the Agency regarding the reintroduction for TYSABRI in the U.S. on or before June 28, 2006. The companies' application for approval of TYSABRI as a treatment for MS is also under review with the European Medicines Agency.

On March 29, 2006, the companies announced they have enrolled and dosed the first patients in the TYSABRI monotherapy safety extension study program in MS. Patients who previously participated in the Phase III MS trials and subsequent safety evaluation are eligible to be screened for entry in this open label multi-center study. Sites throughout Europe, the United States, Canada, Australia, New Zealand and Israel are expected to enroll patients.

About Biogen Idec......"

READ MORE
"After being voluntarily withdrawn from the market in February 2005 with reports of three serious adverse events in patients involved in clinical trials, Biogen Idec and Elan Corporation's multiple sclerosis treatment Tysabri (natalizumab), is poised to return to the market- albeit with restrictions- following approval by a US Food and Drug Administration (FDA) advisory committee.

More time required

Originally the FDA was expected to make its official decision at the end of March. However, both Biogen Idec and Elan have been informed by the FDA that it is extending its regulatory review of Tysabri as a treatment for multiple sclerosis (MS) by up to 90 days. The FDA says it requires additional time to review information regarding the Tysabri risk management plan, says Life Science Analytics Inc (LSA) CEO Dr Robert Naismith. "Under this revised timeline, the companies anticipate action from FDA on or before June 28, 2006. However Biogen Idec and Elan are still expecting FDA action in late March with regard to Avonex with Tysabri therapy."

Tysabri (natalizumab) is a monoclonal antibody for the treatment of multiple sclerosis. According to LSA's online biotech research tool MedTRACK, Biogen Idec reported revenues from Tysabri sales of $US3 million for Q4 2004, while Elan reported sales of $US6.4 million for the same period. However, after two fatal, confirmed cases and one suspected case of progressive multifocal leukoencephalopathy (PML), a rare and frequently fatal demyelinating disease of the central nervous system in two patients that had been receiving Tysabri therapy, it was withdrawn from the market. Both patients had received treatment with Tysabri in combination with Avonex in clinical trials.

Avonex is another Biogen Idec drug for treating MS."

BIOGEN IDEC AND ELAN ANNOUNCE RE-INITIATION OF TYSABRI® CLINICAL TRIAL DOSING IN MS
Biogen Idec - MORE
"Cambridge, MA and Dublin, Ireland - March 29, 2006 - Biogen Idec (NASDAQ: BIIB) and Elan Corporation, plc. (NYSE: ELN) announced today that they have enrolled and dosed the first patients in the TYSABRI® (natalizumab) monotherapy safety extension study program in multiple sclerosis (MS). Patients who previously participated in the Phase III MS trials and subsequent safety evaluation are eligible to be screened for entry in this open label multi-center study. Sites throughout Europe, the United States, Canada, Australia, New Zealand and Israel are expected to enroll patients. This safety extension study is being conducted under a U.S. Food and Drug Administration (FDA) Investigational New Drug (IND) application in the U.S. and similar investigational approvals internationally.

Biogen Idec and Elan had previously voluntarily suspended TYSABRI from the U.S. market and dosing in all ongoing clinical trials based on reports of progressive multifocal leukoencephalopathy (PML), a rare and potentially fatal, demyelinating disease of the central nervous system. Biogen Idec and Elan completed a comprehensive safety evaluation of more than 3,000 TYSABRI patients in collaboration with leading experts in PML and MS. The results of the safety evaluation yielded no new confirmed cases of PML beyond the three previously reported.

On March 8, 2006, the Peripheral and Central Nervous System Drugs Advisory Committee of the FDA voted unanimously to recommend reintroduction of TYSABRI as a treatment for relapsing forms of MS. The companies anticipate action by the FDA regarding the reintroduction of TYSABRI in the U.S. on or before June 28, 2006. The companies' application for approval of TYSABRI as a treatment for MS is also under review with the European Medicines Agency."

[Tysabri] National MS Society

CLICK HERE TO READ MORE: BUSNIESS WEEK..."Biogen Idec Inc.'s top executive was awarded a $1.2 million bonus and a 10 percent salary increase after a year in which the biotechnology company withdrew a promising drug from the market, leading to job cuts and 32 percent drop in its stock price, according to a regulatory filing Friday.

Biogen Idec's board this month also awarded James C. Mullen options to buy 240,000 shares of the company's stock and granted another 180,000 shares of restricted stock, according to the filing Friday.

The Securities and Exchange Commission filing also shows the board awarded $2.83 million in 2005 bonuses to 10 Biogen Idec executives, including Mullen.
Biogen Idec spokesman Tim Hunt said Mullen's compensation is based on several performance measures including the company's earnings and stock performance as well progress in bringing new drugs to market.

"2005 was certainly a challenging year for the organization in many respects, but the company remained focused and disciplined, and made difficult decisions to ensure that we be in a position of strength going forward," Hunt said.

Mullen's $1.2 million performance-based bonus for 2005 is smaller than the nearly $1.35 million bonus the Cambridge-based company's board awarded him in 2004. That year, Biogen Idec's stock rose more than 75 percent in anticipation of the November 2004 introduction of Tysabri, a multiple sclerosis drug that had been widely forecast to become a blockbuster.

But Biogen Idec and its Irish drug development partner Elan Corp. withdrew Tysabri on Feb. 28, 2005, and disclosed the drug may heighten the risk of contracting a rare and often fatal disease of the central nervous system.

Biogen Idec shares plunged more than 42 percent the day the drug was withdrawn. The stock recovered some of the loss as Biogen Idec completed a safety review of Tysabri and applied with federal regulators to resume sales in the United States with a revised label and a plan to address patient risks.

However, Biogen Idec's stock still ended up closing the year at $45.28 per share, compared with $66.61 at the end of 2004. Shares rose 3 cents to close at $44.27 on the Nasdaq Stock Market on Friday.

Tysabri's withdrawal helped trigger a September announcement of plans to cut 650 jobs, or about 17 percent of the work force. Biogen Idec's third-quarter profit fell by 27 percent, partly due to severance expenses from the job cuts. The company is scheduled to release fourth-quarter and full-year earnings on Wednesday.

Mullen has been president and chief executive since the November 2003 merger of drug makers Biogen and Idec -- a deal that preceded a more than yearlong rise in the company's stock before Tysabri's withdrawal."

More: "[Dow Jones] The FDA could provide Elan (ELN) and Biogen Idec (BIIB) with an advisory panel meeting on their suspended MS drug Tysabri within the next few days, says Davy Stockbrokers, assuming a 45-day notice period. Adds March 7 is the most likely date for an FDA advisory panel meeting"

Tysabri® Formerly known as Antegren....The Maryland Center for Multiple Sclerosis

MORE - Forbes.com: " two factors that should help Tysabri are that no patients taking just Tysabri came down with PML, and that existing drugs to fight multiple sclerosis don%u2019t work for 25% of MS patients. For those 100,000 or so patients in the U.S., Kam says Tysabri can greatly improve their quality of life.

These facts, according to Kam, mean that there is no good reason to withhold Tysabri from this group of patients. He says the U.S. Food and Drug Administration will use this as their justification for returning Tysabri to the market as a monotherapy with a big 'black box' warning about the risk of PML on the label.


%u201CWall Street is beginning to agree that Tysabri will return, but Merril Lynch and Citibank both recently reiterated their sell recommendations, both citing their belief that Tysabri will be hard to sell to physicians and MS patients until the risks of PML are better understood,"

DOW JONES...READ MORE: "Stockbrokers says $1.6B in peak sales for suspended MS drug Tysabri are factored into the share price of over $14. It says $1.8B sales are achievable and gives a sum-of-the-parts valuation of up to $15.96. As Tysabri is under review by the FDA, NCB cautions, 'The risk of negative commentary ahead of the (FDA) panel's decision could generate negative sentiment.'"

Executives for Biogen Idec said Tuesday that they expect the U.S. Food and Drug Administration to make a decision by the end of March to clear the market return of the company's recalled drug, Tysabri. In a presentation before investors at the annual J.P. Morgan Healthcare Conference, Biogen executives said that the FDA is scheduled to rule by March's end on whether to approve new labeling for Tysabri that would warn the drug has been linked to an extremely rare but deadly brain disease called PML.READ MORE

MORE: Reuters.com: "The CEO of the U.S. maker of multiple sclerosis treatments said that he saw no sense in a deal...because of their important MS products there would be huge competition issues in Europe and the U.S.'"

Results from the largest trial yet of the selective adhesion molecule inhibitor Tysabri (natalizumab) for Crohn's Disease produced mixed results that raised more questions than they answered.

While the induction phase of the trial failed to demonstrate superiority to placebo, the maintenance phase demonstrated significant benefit over placebo -- but only in patients who responded to the drug initially.

Furthermore, one patient treated with the drug died from a complication associated with it, progressive multifocal luekoencephalopathy, William J. Sandborn, Ph.DM.D.., of the Mayo Clinic here, and colleagues reported in the Nov. 3 issue of the New England Journal of Medicine.

Another death from this complication in a trial of the drug for multiple sclerosis led the manufacturer to withdraw the drug from the market in February of this year. Subsequently more deaths have been reported. The current study had finished in March of 2004.CME Teaching Brief - MedPage Today

MORE-HealthDay: "The potential side effects of a once-promising drug for multiple sclerosis and Crohn's disease are of serious concern and may outweigh any potential benefit, researchers report."

"While PML [progressive multifocal leukoencephalopathy] concerns are legitimate, we believe many neurologists will accept the risk/benefit tradeoff and adoption rates could exceed expectations." MORE - Forbes.com

MORE- The Boston Globe: "Biogen Idec's withdrawal of multiple sclerosis drug Tysabri has forced the company to rely on older drugs to bolster earnings.

Biogen, Elan say no more cases found of rare brain disease....

The news bolstered prospects for Tysabri's return to the market in a limited fashion.MORE - The Boston GlobeBiogen Idec Inc. of Cambridge and its partner, Elan Corp., yesterday said they have completed a safety review of all the patients who took the multiple sclerosis drug Tysabri and did not find more cases of a rare brain disease that infected three patients.

The news bolstered prospects for Tysabri's return to the market in a limited fashion.

''The overall prognosis has improved for Tysabri," said Ian Sanderson, an analyst with S.G. Cowen Securities in Boston. ''It helps things a little bit."

Biogen Idec and Elan, its Irish partner in the drug, halted sales and dosing of Tysabri in February after one patient died of the disease, called progressive multifocal leukoencephalopathy, and another was suspected of contracting it. Of the three patients confirmed with contracting the disease, two died.

Tysabri was approved last November to treat MS and was on sale for only three months. It was also being tested in patients suffering from rheumatoid arthritis and Crohn's disease, an intestinal ailment. The final part of the review revealed yesterday confirmed there weren't any more cases of PML in the 1,500 patients participating in clinical trials for rheumatoid arthritis and Crohn's disease.

''We're encouraged by the findings of the safety evaluation," said Amy Brockelman, a Biogen Idec spokeswoman. ''There's a significant unmet need in multiple sclerosis, and we hope to bring the product back to patients in need."

The two companies last month submitted a revised marketing plan to the Food and Drug Administration, including changed labeling language. The companies asked for ''accelerated review" of the revised plan.

The FDA has 30 days in which to decide whether it will accelerate the review. If it does, the agency would rule on Tysabri within six months, compared to about a year for standard review.

Sanderson said he believed Tysabri would ultimately generate annual revenue of $400 million to $500 million for the two firms. That is considerably higher than some earlier estimates of how Tysabri might perform if it was again approved for sale, but considerably lower than the billion-dollar blockbuster most anticipated when the drug was introduced.

RTE Business -CLICK FOR COMPLETE ARTICLEShares in Elan surged by 20% on the Dublin stock market today after the drugs company and its partner for the development of the MS drug Tysabri, Biogen Idec, said a safety study had resulted in no new confirmed cases of the progressive multifocal leukoencephalopathy (PML) brain disease in MS patients.

The two companies have previously reported three confirmed cases of PML, two of which were fatal.

The ongoing safety evaluation in Crohn's disease and rheumatoid arthritis is on schedule to be completed by the end of the summer, the two companies added. They will then make submissions to regulatory authorities in early autumn.

Elan and Biogen also said that the companies are taking preliminary steps to restart clinical trials in MS.

"The FDA now finds itself in an unenviable position, after receiving an application to clear Tysabri (natalizumab) again, seven months after the multiple sclerosis product was pulled from the market following its links to two fatalities, despite showing clinical efficacy.

And many industry observers expect the agency's risk-benefit analysis to come under scrutiny as the review process moves forward.

"I think they're bound to hold an advisory panel meeting, because these are the exact types of issues you'd want in a public forum," said Elise Wang, an analyst with Citigroup. "And I think there will be a tug of war, with us hearing from patients about how much they need this new therapy and that they're still willing to take the risk."

Still, with the agency's risk-averse nature these days and Tysabri's mysterious connection to progressive multifocal leukoencephalopathy (PML), a rare and potentially fatal demyelinating disease of the central nervous system, the bar is set high for approval.

The supplemental biologics license application from Biogen Idec Inc. and Elan Corp. plc includes final two-year data from the Phase III AFFIRM monotherapy trial and the combination SENTINEL study that evaluated Tysabri with Avonex (interferon beta-1a, also from Biogen Idec), as well as an integrated safety assessment of Tysabri-treated patients completed after the market withdrawal, a revised label and a risk management plan.

Officials could not be reached at either company, but both issued public statements that highlighted the product's "therapeutic benefit" and their "extensive safety evaluation." That was a message often heard from the companies in the months after voluntarily pulling Tysabri from the market and suspending all ongoing clinical trials earlier this year on reports of PML, a side effect that Wang called "very severe." (See BioWorld Today, March 1, 2005.)

Patricia O'Looney, the National Multiple Sclerosis Society's director of biomedical research, called that event a "disappointment." While no test exists to determine one's propensity to the condition, Tysabri patients have been advised to watch for symptoms such as motor weakness on one side of the body, rapidly developing changes in mental function, language disturbance, visual disturbance or changes in behavior or personality.

To date in the partners' subsequent safety analysis, three cases were confirmed, two of which were fatal, but the partners' review uncovered no more. More than 8,000 people have taken the drug.

That positive safety evaluation, in which Cambridge, Mass.-based Biogen Idec and Dublin, Ireland-based Elan consulted with PML and multiple sclerosis experts, has prompted support for Tysabri and its resubmission. But Wang told BioWorld Today that it's still a struggle to discern the "appropriate steps that can be taken to be able to monitor for the risk of this happening." Should the FDA sign off on the resubmission, the risk-benefit equation will fall on the shoulders of patients and prescribers, O'Looney noted. The companies requested a priority review that would result in FDA action in about six months, rather than in 10 months for a standard review.

"We're pleased that no more PML cases were diagnosed," O'Looney told BioWorld Today, "and we're pleased that it's now at the point that the companies are submitting it to the FDA for a hopefully expedited review."

The alpha-4 antagonist first received FDA approval late last year following an accelerated review. The clearance was based on single-year results from AFFIRM and the SENTINEL study; in the former, Tysabri reduced relapse rates by 66 percent compared to placebo, and top-line results from the latter showed a 54 percent reduction in relapse rate for Tysabri combined with Avonex vs. Avonex alone. (See BioWorld Today, Nov. 29, 2005.)

"The efficacy data was exceptionally strong for this drug," Wang said, "so I have a tendency to believe that in the end that it has a chance to come back, but there are going to be some very strict criteria under which it's going to be used."

She noted that it won't be suitable for immunocompromised patients, and likely won't be indicated for combination use with Avonex, as that pairing resulted in two of the PML cases. Wang also pointed to uncertainty about Tysabri's duration of use, as well as a cloudy future for its use in Crohn's disease and rheumatoid arthritis, two other settings in which it was studied.

She added that the drug is not likely to ever hit blockbuster status, as was once touted. Her New York firm, which makes a market in Biogen Idec's securities, has no sales projections for Tysabri in its current forecast model.

O'Looney, who conceded that though Tysabri does not cure multiple sclerosis, called it "an additional option for a physician and patient to talk about in trying to control the progressive aspects" of the disease. She added that should it again receive FDA approval, use of the drug would be determined on a "case-by-case basis" depending on a patient's varying needs. Biogen Idec and Elan will submit a similar data package update to European regulatory authorities as part of an ongoing review process that began last summer. "BioWorld Today

"Biogen Idec Inc. said it has submitted an application to the US Food and Drug Administration seeking a revised license so it can put its multiple sclerosis drug Tysabri back on the market.

The Cambridge company said the application contained the results of its extensive safety review of Tysabri use by multiple sclerosis patients and trial participants, and ''nearly complete" results of its safety review of participants in trials for Crohn's disease and rheumatoid arthritis.
''We are grateful to the MS community for their patience and support over the last several months while we've conducted an extensive safety evaluation of Tysabri in collaboration with leading experts," said Burt Adelman, Biogen Idec's executive vice president of development, in a statement. ''We look forward to working with regulatory authorities during the review process, and ultimately, we hope to provide Tysabri to people living with MS."
A Biogen Idec spokeswoman said the company asked the FDA for accelerated review of the application. If granted, the FDA could respond to the application within six months, rather than 10. A decision on the accelerated review request is expected within 30 days.
Biogen Idec and its partner Elan Pharmaceuticals of Ireland in February voluntarily pulled Tysabri off the market and discontinued clinical trials. One patient taking the drug had died of a rare brain disease and a second was suspected of having contracted it. That patient recovered. A third case of the disease was discovered among patients who had taken the drug for Crohn's disease, an intestinal ailment.
Since then, Biogen Idec has been scouring the records of patients who took Tysabri in clinical trials and during its time on the market. It said it hasn't found any other cases of the brain disease.
Analysts believe Biogen Idec will seek to restart Tysabri sales with a new warning label. Amy Brockelman, a company spokeswoman, declined to comment on the proposed labeling language. ''It's premature to comment on the specifics of the label while we're in discussions with regulatory authorities," she said.
Biogen Idec also filed similar safety review data with the European Medicines Agency. Tysabri hasn't been approved for sale in Europe and the new information will be added to the company's pending application"The Boston Globe

Biogen and Elan on monday said they have submitted new safety data to U.S. regulators on their drug Tysabri, in hopes of getting the withdrawn multiple sclerosis treatment back on the market.more... Reuters.comBiogen Idec Inc. (BIIB.O: Quote, Profile, Research) and Elan Corp. (ELN.N: Quote, Profile, Research) on Monday said they have submitted new safety data to U.S. regulators on their drug Tysabri, in hopes of getting the withdrawn multiple sclerosis treatment back on the market.

The companies, which withdrew the injectable medicine in February, said they have asked the U.S. Food and Drug Administration to review the additional safety data within the next six months. That compares with the standard review period of 10 months.

Biogen Idec and Irish drugmaker Elan voluntarily suspended sales of Tysabri after one multiple sclerosis patient died following treatment with it in combination with Biogen Idec's widely used Avonex drug.

The patient died from a brain disorder known as progressive multifocal leukoencephalopathy (PML) and another patient at the time was suspected of having the condition, which is caused by a virus. Another case was identified in March, and two of the three patients have died.

The appearance of the rare disorder raised the question of whether Tysabri was making patients more susceptible to the so-called JV virus which causes it.

The drug was deemed a potential blockbuster when it was launched in November 2004 because clinical data suggested it was far more effective than existing treatments for multiple sclerosis, including Avonex.

The new data involves more than 3,000 patients with multiple sclerosis, Crohn's disease and rheumatoid arthritis that have taken Tysabri in past trials.

Some patients in the two late-stage multiple sclerosis trials took Tysabri by itself, while others took it in combination with Avonex.

"The companies said late Tuesday they expect to complete their safety review of Tysabri "in the coming weeks." Then they expect to seek approval to reinstate the drug as a treatment for multiple sclerosis. After the companies withdrew Tysabri, they embarked on an extensive review among patients who had participated in clinical trials for MS, Crohn's and rheumatoid arthritis. They suspended all clinical trials of the drug.

The safety review of the Crohn's disease and rheumatoid arthritis patients will be completed soon. On Aug. 9, the companies said they found no new confirmed cases of PML among MS patients.

The companies said 91% of the more than 2,000 MS patients tested in clinical trials took part in the follow-up safety review, which also included an examination of any reports of potential PML in patients receiving Tysabri after the drug reached the U.S. market in November.

Tysabri had been approved for relapsing-remitting MS, the most common form of the disease at the time of diagnosis. It is characterized by acute symptoms or a worsening of neurological functions that can occur intermittently. These symptoms can weaken or disappear for months or years between relapses.

The companies didn't say how many Crohn's and rheumatoid arthritis patients are being evaluated. Previously, the companies said the MS patients contracting the PML side effect took both Tysabri and Avonex, another MS drug from Biogen Idec, for more than 24 months. The Crohn's Disease patient took Tysabri and immunosuppressant drugs, a common treatment for certain inflammatory diseases."

www.thestreet.com

Drug maker Biogen Idec Inc. on Thursday said it will lay off 650 workers, or about 17 percent of its work force, as part of a plan to reduce annual expenses by $200 million to $300 million.

The Cambridge-based biotechnology firm, seeking to regain its footing after withdrawing a multiple sclerosis drug over safety concerns, said it also plans to sell a San Diego manufacturing plant as well as the rights to Amevive, a psoriasis drug that generated $43 million in sales last year.

James C. Mullen, Biogen Idec's chief executive and president, said the company is "well-poised for near-term success'' but believes for the long term that it must cut programs "unlikely to create significant value.''

Biogen Idec announced the restructuring after its shares closed down 3 cents at $42.44 on the Nasdaq Stock Market, where the stock has traded in a 52-week range of $33.18 to $70.

Biogen Idec said the cuts to 650 positions worldwide will mostly occur by the end of the year, spread across various departments and locations. Of the total jobs to be cut, 250 will come from the company's Cambridge headquarters, which now has 1,700 employees.

Biogen Idec expects to take a pretax charge against its earnings of $30 million to $40 million to cover severance and restructuring costs resulting from the cuts.

The company has recently remained profitable despite its decision in February to withdraw the multiple sclerosis drug Tysabri. Biogen Idec developed the drug with its Irish partners, Elan Inc.,

The drug may heighten the risk of contracting a rare and often fatal disease of the central nervous system. The companies are completing a review of the drug's safety, and hope to report back to federal regulators by month's end in hopes that it will be found safe to return to the market, likely with a more restrictive warning label.

The drug was withdrawn after it was linked to two cases of a brain disease called progressive multifocal leukoencephalopathy, or PML. One of those patients died. On March 30, Elan and Biogen announced that a Crohn's sufferer who had been taking Tysabri also had died of PML

www.sanluisobispo.com

The head of Biogen Idec Inc. said in an interview Wednesday his company will recommend to regulators within a month that the warning label be strengthened on a multiple sclerosis drug the company hopes to return to the market despite safety concerns.

James Mullen said Biogen Idec will likely recommend that Tysabri include warnings about three cases of an often-fatal brain disease that were confirmed after clinical trials of the drug, which was withdrawn from the market Feb. 28 despite hopes that it would become an important new tool in treating MS.

Mullen said the revised label that the company will propose to the U.S. Food and Drug Administration also will warn about risks for patients who have weak immune systems and therefore could be more susceptible to contracting the disease, called progressive multifocal leukoencephalopathy, or PML.

However, Mullen said the label language his company will suggest to FDA when it seeks permission to resume marketing Tysabri will acknowledge that scientists don't yet understand precisely how the bioengineered drug put the three patients who contracted PML at risk of contracting the rare disease. Two of those patients died.

"I think it's important for us to not overstate what we know," Mullen, Biogen Idec's chief executive and president, said in an interview with The Associated Press at the company's Cambridge headquarters. "We want to be concrete about what we know and what we don't know."

Mullen said Biogen Idec and its Irish partner in Tysabri, Elan Corp., plan to submit findings from their review of the drug's safety to the FDA by the end of September.

The companies had previously said the report would be submitted sometime in the fall so the FDA could review whether Tysabri can safely return to the market. Some industry analysts have said strong warnings on Tysabri's label could ruin the drug's chances of becoming a commercial success.

Mullen said it is "highly unlikely" the FDA will complete its own review by the year's end, but he said the regulators are "interested in a thorough but expeditious review of determining whether this can brought back to the market in the near future or not."

FDA spokeswoman Lenore Gelb declined to comment Wednesday.

Biogen Idec and Elan said Aug. 9 that more than 2,000 patients with multiple sclerosis who took Tysabri in clinical trials had been screened for PML as part of the companies' safety review, but no new cases were found.
The companies are close to finishing a similar review of about 1,500 people who took Tysabri in clinical trials to test its effectiveness in treating Crohn's disease and rheumatoid arthritis.
After reviewing one year of data from planned two-year trials, federal regulators in November approved Tysabri for sale to the 350,000 American sufferers of MS, a debilitating and incurable disease in which the body's immune system turns rebellious, attacking, inflaming and damaging its own nerve tissue.
The drug was withdrawn about three months after its approval, causing Biogen shares to plunge more than 42 percent the day of the announcement while Elan's stock fell 70 percent.
"We hope there is a pathway back to the market," Mullen said. "We think that unless we see some new surprises, that the risk-benefit profile for this product certainly warrants it being used for MS.
"We've got probably hundreds of letters from patients saying, 'Tysabri changed my life. I've got no other options. I'll sign whatever waiver I need to get access to this product.'" Boston.com

Loosely defined, Alpha (4) beta (1) integrin is a protein on the surface of immune cells that allows them to pass into the central nervous system (CNS). In the auto-immune model of multiple sclerosis, these immune cells then mistakenly attack myelin, causing inflammation and the cascade that leads to scarring (or sclerosis) of the CNS.
A drug wich binds with the alpha (4) beta (1) integrin protein will prevent the immune cell from entering the CNS. The auto-immune theory would then predict that inflammation would be circumvented as the immune cells are not present in the CNS to attack myelin.

Tysabri, though currently unavailable whilst the PML issue is worked out, is the first alpha (4) beta (1) integrin binder available for multiple sclerosis patients. A new and very interesting study shows that prolonged exposure to an alpha-integrin inhibitor allows spontaneous remyelination to occur in the mouse model of MS versus vehicle alone (no active drug). In other words, preventing the immune system cells from reaching the CNS allows the body to repair damage better than when the immune cells are present.

Specifically, after 40 days of treatment with an alpha-integrin inhibitor (not necessarily Tysabri, though the study was partially funded by Tysabri's part-owner Elan...), nearly 90% of the mouse lesions showed some form of remyelination. Further details include the repair occurring in just half of the total lesion areal, and half of the mice regaining motor function lost prior to treatment. The control mice did not show significant signs of repair or regaining of function. The study concludes: "Therefore, prolonged inhibition of CNS inflammation, in the absence of targeted myelin repair, facilitates mechanisms of spontaneous remyelination."

As with any study that is performed on mice, please remember that the mouse model of MS is oftentimes very different than the human version, and thus results on the animals do not necessarily predict results on humans. Likewise, prolonged inhibition of immune cell trafficking might also have unintended consequences, e.g., PML or another new study that shows chronic inhibition initially helps, then exacerbates colitis in mice.

In any case, this is an important study and shows that there is hope for repair of damage, particularly when the immune cells are mostly prevented from trafficking into the CNS.This Is MS --...Click to read entire article...

The employees work at the Oceanside biotech manufacturing plant built by Biogen Idec, based in Cambridge, Mass., to manufacture a drug for multiple sclerosis called Tysabri. The company sold the plant to South San Francisco-based Genentech in June for $408 million, after sales of Tysabri were suspended after reports of illness possibly caused by Tysabri.

Genentech is readying the new Oceanside plant to produce Avastin, a drug for colorectal cancer. Avastin belongs to a type of drug known as monoclonal antibodies that precisely target diseased cells.

Biogen Idec built the plant to manufacture Tysabri, also a monoclonal antibody, which relieves symptoms of multiple sclerosis. The plant would have doubled the production capacity for Tysabri, sold by Biogen Idec and the Irish drug company Elan Pharmaceuticals...Click to read...

From: Gordon Francis, MD, Vice President, Neurology Therapeutic Market, Elan Pharmaceuticals:

"Dear Healthcare Professional,

In an effort to keep you informed of new developments, Biogen Idec and Elan
Pharmaceuticals are providing an update related to the ongoing safety evaluation of
TYSABRI® (natalizumab). On August 9, 2005, we announced that findings from our
ongoing safety evaluation of TYSABRI revealed no new confirmed cases of progressive
multifocal leukoencephalopathy (PML) in multiple sclerosis (MS). The Crohn’s disease and
rheumatoid arthritis safety evaluation is on track to be completed by the end of the summer.

More than 2,000 MS clinical trial patients were eligible for the TYSABRI safety evaluation.
91% of these patients chose to participate in the evaluation. Of these participating patients,
99% had a neurological exam, and 98% had an MRI. The safety evaluation also included the
review of any reports of potential PML in patients receiving TYSABRI in the commercial
setting.

On February 28, 2005, we announced the voluntary suspension of TYSABRI from the US
market and all ongoing clinical trials based on reports of PML, a rare and potentially fatal
demyelinating disease of the central nervous system. The companies have previously
reported three confirmed cases of PML, two of which were fatal. We remain committed to
completing this safety evaluation and look forward to working with regulatory agencies to
determine the appropriate path forward for TYSABRI. Based on expected completion of the
safety assessment by the end of the summer, we anticipate making regulatory submissions to
the U.S. Food and Drug Administration (FDA) by early fall.

Thank you for your patience and continued support over the past few months. We will
continue to inform you of new developments and changes. For additional questions, please
contact Medical Information at"

click for article: Reuters.co.ukA safety study for Elan Corp.'s (ELN.I: Quote, Profile, Research) (ELN.N: Quote, Profile, Research) multiple sclerosis drug Tysabri has found no new confirmed cases of the brain disease that prompted the Irish company to pull the drug, it said on Tuesday, and its shares soared 21 percent.

CLICK FOR ARTICLE: U.S. Food and Drug Administration
What is Tysabri?
Tysabri is a monoclonal antibody that binds to a protein called alpha-4-integrin. Integrins are found primarily on the surface of white blood cells, and play a role in immune system activity.

What is Tysabri used for?

Tysabri is approved to treat patients with relapsing forms of multiple sclerosis (MS) to reduce the frequency of exacerbations. It was approved based on results achieved after approximately one year of treatment in ongoing controlled trials.

What is Multiple Sclerosis?
Multiple sclerosis (MS) is a serious disease in which the immune system attacks the person's brain and spinal cord. The disease causes a wide range of symptoms including fatigue, difficulty walking, numbness, and vision problems. MS frequently progresses to severe disability and/or death. Relapsing MS is the most common form of this disease.

How is Tysabri given?

Tysabri is given by intravenous infusion once every 4 weeks.

Why is marketing of Tysabri being suspended?
A patient with MS in a long-term clinical trial of Tysabri recently died from progressive multifocal leukoencephalopathy (PML), a rare neurologic disease; a second patient with MS in the same trial who was receiving Tysabri has a confirmed diagnosis of PML. Because the relationship between use of Tysabri and PML is not clear, Biogen Idec, the manufacturer of Tysabri, has voluntarily suspended marketing, as well as dosing of Tysabri in clinical trials, until the relationship is better understood. The FDA concurs with this decision.

What other steps has the manufacturer taken?

The manufacturer is notifying physicians of these cases and informing them that use of Tysabri should be discontinued until further notice. Similar notices are being sent to physicians who are studying Tysabri as part of a clinical trial. Biogen Idec is recommending that all patients who have received Tysabri and have signs and symptoms suggestive of PML be evaluated. Any potential case should be reported to Biogen Idec, or to the FDA’s MedWatch reporting system by telephone (1-800-FDA-1088), facsimile (1-800-FDA-0178), the MedWatch Web site at www.fda.gov/medwatch, or mailed to MedWatch (HF-2, 5600 Fishers Lane, Rockville, MD 20853-9787). The manufacturer is reviewing the records of all patients who have received Tysabri in a clinical trial and evaluating these patients to determine if there any other cases of PML in this population. Biogen Idec is also convening a panel of medical and scientific experts on this condition to give advice on appropriate steps, including how to assess patients who have received Tysabri and who may have developed undetected early-stage PML. The FDA will maintain close contact with the manufacturer during this process and issue further information as it becomes available.

What kinds and numbers of patients have received Tysabri?

Patients have received Tysabri either in a clinical trial or, since its approval in November, 2004, through their personal physician. Clinical trials of Tysabri include patients with MS, Crohn’s disease, and rheumatoid arthritis. About 3000 patients have received Tysabri in clinical trials; over 1700 have received it for at least a year and approximately 1100 for over two years. Outside of a clinical trial, Tysabri is only approved for patients with MS. According to Biogen Idec, outside of clinical trials, approximately 5000 patients with MS have received Tysabri through their primary physician; however, because Tysabri was approved only recently, these patients have only received at most a few doses of Tysabri.

Have there been any cases of PML in the 5000 patients receiving Tysabri through their primary physician?
There have been no cases of PML reported or detected in patients receiving Tysabri outside of a clinical trial and no cases outside of the trial in patients with MS.

How long will this suspension last?
The availability of Tysabri in the future will depend on the analyses of the data being obtained by the drug’s manufacturer.

Why was marketing suspended because of just two confirmed cases of PML?

Although these two confirmed cases of PML do not automatically mean that Tysabri causes PML, and additional information needs to be obtained to fully understand the connection, if any, between Tysabri use and PML, the FDA and Biogen Idec are concerned about the possibility that other patients who have received Tysabri may have developed undetected early-stage PML. PML is a very rare and potentially fatal condition that is not known to occur in patients with MS. Until this situation is better understood, the manufacturer has voluntarily suspended marketing of Tysabri and its use in clinical trials. The FDA concurs with this decision. The manufacturer is convening a panel of medical and scientific experts on this condition to give advice on appropriate steps, including how to assess patients who have received Tysabri and who may have developed undetected early-stage PML.

How common is PML?

In the general population, PML is extremely rare, and virtually never occurs in individuals with normal immune systems. 1 – 5% of AIDS patients may be diagnosed during their lifetime; PML has also occurred in organ transplant recipients who have received immunosuppressive medications, as well as cancer patients.

What causes PML?
PML is thought to be caused by a virus called JC virus (JCV). Most people are exposed to this virus in childhood and carry it in a dormant state but never develop illness. PML occurs almost exclusively in individuals with suppressed immune function who carry JCV. The immune suppression allows the virus to cause disease.

Is PML contagious?
PML is not thought to be contagious, and isolation precautions are not needed.

Is there any treatment for PML?

There is no known effective treatment for PML, although reversing immune system suppression may slow or arrest the progress of the disease.

Does Tysabri cause PML?
At this point, the connection, if any, between Tysabri use and PML is not known.

Is PML more common in patients with MS?
Although the symptoms of PML may appear similar to those of MS, there does not appear to be a direct relationship between these two diseases, and patients with MS are not thought to be at higher risk than the general population for development of PML.

Did the patients who developed PML have other possible reasons to develop this disease?
Neither patient had typical risk factors for PML. Both patients were receiving Avonex (interferon beta-1a), another approved treatment for MS, at the same time that they were being treated with Tysabri. Prior to approval, the manufacturer of Tysabri had studied its use in combination with Avonex; no cases of PML were observed in patients receiving the combination. The use of interferons, including Avonex, has not been associated with PML. FDA has analyzed data in its post-marketing database and not found any cases of PML reported in patients receiving a beta interferon. It is not known if Tysabri in combination with a beta interferon might cause PML.

How long has the FDA known about this situation?

FDA was first provided with preliminary information about these cases by Biogen Idec late on the afternoon of Friday, February 18. Details of the cases became available over the next week.

What is the FDA doing about this situation?
In addition to issuing this advisory, FDA has been in close contact with the manufacturer of Tysabri, and concurs with their decision to voluntarily suspend marketing of Tysabri and dosing of Tysabri in clinical trials. FDA is also imposing a clinical hold on trials of Tysabri, legally prohibiting further investigational use of Tysabri until more information is available. Although these events occurred in clinical trials, FDA has also been analyzing data from its post-marketing database to better understand any possible connection between Tysabri, Avonex, and PML. FDA is also working with the manufacturer to determine the best methods for assessing patients who have received Tysabri in order to assure their safety and understand the connection, if any, between Tysabri and PML. FDA will issue further information as it becomes available.

When was Tysabri approved?

Tysabri received accelerated approval in November 2004.

What does it mean that Tysabri received accelerated approval?
Accelerated approval is a program the FDA developed to make new drug products available for serious or life threatening diseases when they appeared to provide a benefit over available therapy. Tysabri was approved on the basis of a clinical study showing that Tysabri, when added to Avonex, reduced the risk of exacerbations by 54% compared to Avonex alone. Tysabri by itself reduced the risk by 66% compared to placebo in another clinical study. These results represented an important and meaningful benefit for patients with MS. At the time of approval, approximately 1,100 patients with MS had received Tysabri for one year or more. As a condition of approval of Tysabri, the manufacturer was required to continue these clinical trials through a period of two years to show that the drug continues to provide benefit. The two cases reported here occurred in patients in the continuation phase of these trials.

Why didn’t the FDA wait longer before approving Tysabri?
The results shown in the clinical trials of Tysabri showed an important and meaningful benefit in the treatment of MS, a serious disorder that can lead to permanent disability or death. The efficacy results, in combination with the safety profile of Tysabri observed in clinical trials, supported accelerated approval. This allowed Tysabri to be made available to patients with MS earlier than would be the case for traditional approval. No cases of PML were observed in the clinical trials supporting the approval of Tysabri.

Shouldn’t the FDA have known this might happen?
PML is a rare condition that does not occur even in the vast majority of patients, even those with suppressed immune systems. During the review of Tysabri, the FDA conducted an intensive analysis of possible adverse events that might be connected to effects of Tysabri on the immune system. No cases of PML were seen in the clinical trials that were the basis for approval of Tysabri, nor were infections characteristic of immunosuppression observed. However, for any approved therapy, new and unexpected adverse events may occur that were not seen in clinical trials. In the case of Tysabri, required post-marketing studies were ongoing and facilitated rapid reporting of and response to these events.

Are patients with MS at more risk of developing PML if they have been treated with Tysabri for a long time?
The relationship, if any, between length of treatment with Tysabri and development of PML is not known at this time.

What are other adverse reactions have been reported with Tysabri?
The most frequently reported adverse events with Tysabri in clinical trials were infections, severe or life threatening allergic reactions, depression (including thoughts of suicide), and gallbladder problems. These events occurred at rates ranging from 0.8% to 2.1%. No cases of PML were observed in the clinical trials used to support approval of Tysabri.

I’ve received Tysabri for my MS. Am I going to develop PML?
Although the risk, if any, of PML in patients receiving Tysabri is not known, it is important to recognize that only two confirmed cases of PML have been identified from among over 8000 patients who have received Tysabri. Patients should, however, discontinue use of Tysabri until further notification.

NEJM -- linkLetter from Biogen Idec

link for complete article- Forbes.comMorgan Stanley reiterated an "underweight" rating on Elan (nyse: ELN - news - people ), saying considerable uncertainty still exists around the future of Tysabri, the company's multiple sclerosis treatment.

"We still believe there is significant risk that Tysabri never returns to the market," Morgan Stanley said. The research firm said Elan and partner Biogen Idec have to conduct long-term studies to get the product back on the market, and that if the product does return, safety concerns may minimize its impact on earnings.

Assessing the Withdrawal of Natalizumab - Journal Watch Neurology"The stunning chain of events concerning natalizumab has dealt a shocking blow to many patients who had pinned their hopes on what appeared to be an extremely effective new agent. It also has dashed the hopes of clinicians and discouraged hundreds of natalizumab investigators worldwide. Why PML emerged in patients without other opportunistic infections remains a mystery. JC virus, believed to reside in as many as 80% of clinically asymptomatic adults, probably is harbored in B cells within the bone marrow. It is frequently shed in urine. The mechanism by which it is activated to cause neurologic disease in natalizumab recipients remains unclear and is being investigated."...Dr. Miller is Professor of Neurology, Mount Sinai School of Medicine, and Medical Director, Corinne Goldsmith Dickinson Center for Multiple Sclerosis, New York City.

LINKThe family of a woman who died in February after participating in a clinical trial of multiple-sclerosis medications has filed a lawsuit against the manufacturers of the drugs.

The woman's family has sued Biogen Idec Inc. of Cambridge, Mass., and Elan Pharmaceuticals of San Francisco, claiming they knew the drug combination was dangerous.

Anita Smith died of progressive multifocal leukoencephalopathy, or PML, a rare and potentially fatal nervous-system disorder the lawsuit alleges has been linked to the drugs Tysabri and Avonex.

"Before Tysabri was approved, its manufacturers were aware that the drug's use, in combination therapy with Avonex, was dangerous," said Jerrold Parker, an attorney with Parker & Waichman LLP, the firm that filed the suit in Massachusetts Middlesex Superior Court on behalf of the family. The suit seeks unspecified monetary damages.

"This blatant disregard for patient safety caused tremendous suffering for Mrs. Smith and her family," Parker said in a statement. "It certainly appears that combination therapy was proposed by Biogen in an effort to maintain the relevance of Avonex in the marketplace following Tysabri's introduction."

Biogen spokesman Jose Juves said the company was just beginning to review the lawsuit.

"Our sympathies go out to the Smith family that this unforeseen event occurred during the clinical trial," Juves told United Press International. "When Biogen Idec was first alerted to a potential case of PML we quickly and decisively halted all dosing in clinical trials and began an extensive and still ongoing safety evaluation."

Tysabri is an immunosuppressant that was approved by the Food and Drug Administration last November. It was taken off the market only three months later, in February, after two people, including Smith, developed PML after receiving the drug.

Smith, who had participated in clinical trials of the drug in 2002, died Feb. 24, 2005. In that 2002 study, Tysabri was being combined with Avonex, another multiple-sclerosis drug manufactured by Biogen.

The drug combination may be dangerous because it can increase the average concentration of Tysabri in the body by 86 percent, the suit alleges. The high levels of Tysabri can then lead to the development of PML, the suit charges.

The suit also notes that in its review of the drug before approving it the FDA found after the sixth dose the drug combination can significantly reduce the rate of clearance of Tysabri and increase the half-life, which leads to elevated concentrations in the body. Smith had received 30 doses of the drug combination.

Biogen and Elan have acknowledged that as many as three cases of PML may have occurred in patients taking Tysabri, Juves said, but they have not yet determined if Tysabri caused the fatal condition.

"One of the things we're looking at is whether it's linked to PML," Juves said.

Parker maintained the drug does cause PML.

"There clearly is a link between Tysabri and PML when it is used in combination with Avonex," he told UPI.

Parker said he suspects more instances will be uncovered of patients developing PML after taking Tysabri. He said his firm is reviewing "several" additional cases involving Tysabri, including one patient who developed PML and one who developed an opportunistic infection. He said he may file additional lawsuits against the companies.

The companies announced earlier this week that a recently completed phase III trial showed the drug combination reduced the risk of disability progression in multiple-sclerosis patients by 24 percent and led to a 56-percent reduction in clinical relapses compared to Avonex alone.

Asked if the company planned to attempt to bring Tysabri back onto the market, Juves said, "We're going to await the outcome of our safety evaluation."

CLICK HERE FOR LINK TO COMPLETE ARTICLEElan Corporation, plc and Biogen Idec announced today that ENCORE, the second Phase III induction trial of TYSABRI(R) (natalizumab) for the treatment of moderately to severely active Crohn's disease (CD) in patients with evidence of active inflammation, met the primary endpoint of clinical response as defined by a 70 point decrease in baseline Crohn's Disease Activity Index (CDAI) score at both weeks 8 and 12.On February 28, 2005, Elan Corporation, plc and Biogen Idec 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 potentially fatal, demyelinating disease of the central nervous system. Elan and Biogen Idec's comprehensive safety evaluation concerning TYSABRI and any possible link to PML is ongoing. At the time of the dosing suspension, all ENCORE study patients had completed dosing based on the study protocol and collection and analysis of data followed.

...Interaction with Avonex may be fatal

LINK - The Boston Globe

Elan Corp. and Biogen Idec Inc.'s multiple sclerosis drug Tysabri may have killed patients because interaction with another Biogen product, Avonex, led to a buildup and overdose of the medicine, an NCB Stockbrokers analyst said.

An interaction of Tysabri, recalled Feb. 28, and Avonex, an older MS drug sold by Biogen ''essentially leads to almost double the intended Tysabri concentration after only 20 weeks," NCB analyst Orla Hartford said yesterday in a note to investors. ''Patients on Tysabri alone did not accumulate the drug."

The effect Avonex has on Tysabri will likely ''form a central part of the case made to the FDA for Tysabri's relaunch," she said. Hartford, who analyzed data submitted to the US Food and Drug Administration during the approval process, expects the treatment to be reintroduced in 2006.

''Elan's continuing with the review, which is on track, and will comment when it has been completed," said Elizabeth Headon, a spokeswoman for Elan at Murray Consultants.
Tysabri was withdrawn after being linked to progressive multifocal leukoencephalopathy, a rare neurological disease, in two patients, both of whom were taking a combination of the two drugs. Elan and Biogen Idec are reviewing medical records of patients who have taken the drug. The companies will meet with the FDA to determine whether the drug can be sold again.
''The efficacy of Tysabri in treating multiple sclerosis is undeniable and we continue to believe that Tysabri will return to the market as a significant therapy," Hartford said.
Shares of Biogen rose 56 cents yesterday to close at $34.65 on the Nasdaq Stock Market.
Tysabri is the cornerstone of Elan chief executive Kelly Martin's plan to reach profitability and repay debt due in 2008 and 2011. He said in May he's confident the drug will return to the market.

Hartford said that over a sustained period of time, Tysabri accumulated in the system partially because the body is less able to process it, which leads to an ''overdosing," she said.
The Tysabri accumulation may have led to a suppressed local immune system in the brain and may have been a key predisposing factor in the two cases of PML seen in combination therapy, Hartford said.

A third patient, identified in March, wasn't taking Avonex, but was on azathioprine, another immunosuppressive drug. Other possible cases have been reported to the FDA, but they haven't been confirmed.

MSAA News: LINKSeveral articles on the topic of Tysabri® (natalizumab) and the possible development of progressive multifocal leukoencephalopathy (PML) were posted on the New England Journal of Medicine's website on June 9th . While these case studies and editorials were originally to be published in July, news of a suspected fourth case of PML in a Tysabri-treated patient prompted the journal to post the articles in advance online. More recently (on June 13 th ), The Wall Street Journal announced a possible fifth case of PML, involving a woman who has been hospitalized.

To review, Tysabri was given early approval in November 2004 by the Food and Drug Administration (FDA) for the treatment of MS. The drug had shown initial success in clinical trails and was expected to be a strong candidate for the long-term treatment of MS. The drug was suspended, however, in February 2005 after PML (a brain virus that is often fatal) was confirmed in two patients taking both Tysabri and Avonex® (interferon beta-1a).

The first patient died and the second patient appears to be improving. A third case was discovered upon the re-examination of a patient who took Tysabri in the treatment of Crohn's Disease and died in 2003. An investigation is now underway regarding the possible fourth and fifth cases of PML.

A letter from three doctors at Biogen Idec (makers of Tysabri) may also be viewed on the New England Journal of Medicine's website at http://content.nejm.org/ . The correspondence notes that while little is known about PML and JC virus, studies suggest that PML is not uniformly fatal, and cases of PML may be preceded by the JC virus. Additionally, a test may be able to determine the presence of the JC virus in a patient's plasma. The doctors speculate that through early diagnosis, Tysabri treatment could be discontinued in time to allow patients to recover, providing hope for some that Tysabri may return to the marketplace.

According to The Wall Street Journal's press release dated June 9, 2005, Dr. Joseph Berger from the University of Kentucky Medical Center has some concerns. He warns that while the idea of early diagnosis and recovery is a possibility, it does carry associated risks. For instance, the studies being reviewed only have a few years of data available, and the risk of developing PML could potentially increase after several years of treatment. Additionally, Tysabri remains in the body for three months after treatment is stopped, which could increase the risk of developing PML even if the treatment is discontinued following the discovery of the JC Virus.

Biogen Idec is conducting a large analysis of thousands of patients who took Tysabri. Results of this evaluation are expected to be available by the end of the summer.

Information for this writing was obtained from the New England Journal of Medicine (http://content.nejm.org/ ), Reuters, and The Wall Street Journal.

HealthDay LINK FOR FULL ARTICLEDetailed reports shed new light on why three patients who were treated with the biologic drug Tysabri for either multiple sclerosis or Crohn's disease developed severe brain infections.

In three scientific briefs and two editorials released Thursday by the New England Journal of Medicine, the specifics of each case are laid out and analyzed by experts in the field. The journal released the package early after a possible fourth case was reported last week. Two of the first three patients have died.

"This is the first time we've had a peer-reviewed report of the information provided by the company to the public," said Dr. John R. Richert, vice president for research and clinical programs for the Multiple Sclerosis Society. "It is the first time we have been able to peruse details of the cases."

Although the news of the infections first came as a blow to those in the MS community, Richert noted that some of the details in these case reports leave open the possibility that Tysabri might one day return to the market if screening methods are found to detect which patients might be susceptible to the brain infection.

Reuters Health LINKA possible fifth case of a rare and often fatal brain infection linked to the multiple sclerosis drug Tysabri has been reported to federal regulators, the Wall Street Journal reported on Monday.

The case was reported on May 16 through the Food and Drug Administration's Adverse Event Reporting System, which collects reports of possible drug reactions from physicians and drug makers. An FDA spokeswoman told the Journal that these reports do not represent confirmed cases.

LINKAccording to Dr. Jeffrey Drazen, the editor-in-chief of NEJM, while he sees a link between Tysabri and the onset of PML, further study is needed to determine whether the drug's benefits justify its risks. Tysabri is also known as natalizumab.

He says natalizumab does present a dilemma, as though it appears to be a promising therapy for multiple sclerosis and has raised the hopes of patients, the complication of PML can be fatal.

Drazen made his comments in an editorial about the formidable risks that clinical trial patients face. The editorial accompanied the analyses of data collected from three clinical trial patients who used Tysabri and subsequently contracted PM, two died from the disease. He says that though the association between natalizumab and the occurrence of PML seems clear, the level of that risk of PML per year of exposure is unknown.

PML is believed to be caused when a virus called the JC virus is reactivated and attacks the brain. and medical experts estimate that up to about 80% of the public carry the JC virus, which almost always remains dormant. PML, which is extremely rare, is most often seen in patients who are severely immuno-suppressed, such as those suffering from advanced AIDS, and is often fatal.

Other experts speculate that PML victims might stand a better chance of recovering if Tysabri was discontinued in the very early stages of the disease.

Biogen researchers hope that Tysabri could return to the marketplace if patients are strictly monitored for the onset of PML.

They say it is possible that testing for the appearance of JC virus in blood and discontinuing the natalizumab therapy would allow patients to recover.

The Biogen team say they are committed to a thorough evaluation of the safety profile of natalizumab.

Drazen has praised Biogen specifically for its handling of the clinical trial patients.

Biogen and Elan suspended all sales and testing of Tysabri in late February after two patients using the drug in a clinical trial were reported to have contracted PML. A third PML victim, also from a clinical trial, was identified in March. A fourth suspected case of the disease was reported to the FDA recently.

According to Biogen and the FDA, of the three confirmed PML cases, two of the patients have died, while a third survived, the fourth suspected victim is also alive.

Three of the patients, who suffered from multiple sclerosis, used Tysabri along with another Biogen drug, Avonex. A fourth patient, who suffered from Crohn's, had been taking Tysabri, along with a variety of other medications for his condition.

Since the discovery of the first two cases in February, Biogen and Elan have carried out a comprehensive medical review of the 5,000 patients who took Tysabri, to identify the trigger for PML. They hope to have the review completed by late summer, and will then discuss with the FDA whether Tysabri should be put back on the market and in what capacity.

MedlinePlus: LINK(Reuters Health) - Tysabri (natalizumab), an antibody treatment used for multiple sclerosis and Crohn's disease, has been linked to another case of progressive multifocal leukoencephalopathy (PML), a serious neurologic disease, bringing the total number of cases to four.

In light of this newest case, The New England Journal of Medicine (NEJM) today released early reports describing the first three cases.

In response to the additional report, Amy Brockelman, spokesperson for Biogen Idec, the maker of Tysabri, told Reuters Health that "we are reviewing any and all suspected cases of PML as part of our extensive safety evaluation and hope to have findings from that evaluation available by the end of summer."

All sales and marketing of Tysabri were suspended on February 28, and clinical trials of the drug have been halted, she added.

The fourth case was reported by the Boston Globe, which obtained its information from the FDA's adverse event reporting database, Brockelman said. But so far, only two of the cases have been fatal, she added. The fourth case is not yet confirmed.

According to the reports in the NEJM, two of the confirmed cases involved patients with multiple sclerosis, while the third occurred in a patient with Crohn's disease.

In a related editorial, Dr. Joseph R. Bergerat the University of Kentucky, Lexington, and Dr. Igor J. Koralnik, from Harvard Medical School in Boston, explain that PML is a rapidly progressive, often fatal brain disorder caused by infection of the nervous system with JC virus, a microbe that nearly everyone becomes infected with in childhood, but that usually remains dormant, causing no problems.

"The occurrence of PML in this setting was totally unexpected," they write, "since it almost invariably occurs in" patients with severe immune suppression, such as those with AIDS or organ-transplant recipients.

JC virus was detected in blood and brain fluid samples from the three confirmed case patients.

Bergerat and Koralnik suggest that ongoing measurement of JC virus levels, with subsequent dose adjustment or drug discontinuation, could prevent the development of PML in patients treated with drugs like Tsyabri.

In their case report, Dr. Annette Langer-Gould, from Stanford University School of Medicine in California, and her colleagues note that there was MRI evidence of PML one month before symptoms developed in the patient with Crohn's disease.

"More frequent MRI monitoring of patients who receive (Tysabri) may be warranted," they write.

LINKA Biogen Idec official has sent an e-mail message to neurologists suggesting that a suspected fourth case of a brain infection in a patient taking the drug Tysabri was a false alarm, according to two doctors who received the message. The e-mail message said the patient was shopping when she heard news reports last week that she had the potentially fatal infection.

Word of the e-mail message emerged on the same day The New England Journal of Medicine released several papers on the three people who contracted the rare but deadly viral infection after taking Tysabri, a multiple sclerosis drug.

The papers suggested, at least to Biogen, that it might be possible to detect the virus in blood early enough to avert serious consequences of the infection. If that were the case, it might be possible for the drug to return to the market. Biogen's interpretation was presented in a letter that will be published with the documents released today in the July 28 issue of the journal.

The possibility of a fourth case, first reported by The Boston Globe last week, was based on a report made by a health professional to the Food and Drug Administration.

This week, though, Dr. Michael A. Panzara, a medical official at Biogen, sent an e-mail message to some neurologists casting doubts on the report. Dr. Norman Kachuck of the University of Southern California, one of those who received the e-mail message, said it quoted from a message sent by the doctor treating that fourth suspected patient.

"I just spoke to my patient's daughter, 11:50 a.m., and she is alive and out shopping," the treating doctor wrote, according to Dr. Kachuck

Dr. Douglas R. Jeffery, who runs the multiple sclerosis clinic at Wake Forest University, said he had also received the e-mail message, but still had concerns. "It's fishy," he said, "because if that's the case, why didn't they say that to The Boston Globe right upfront?"

A spokeswoman for Biogen Idec declined to confirm or deny the existence of the e-mail and said the company would not comment on individual patient cases. She said experts were examining the records of all patients who took the drug and would compile a complete report, which might be ready by the end of summer.

The medical journal's papers provided details on the first three patients. Doctors in Belgium looked at stored blood samples taken over time from one patient who died from P.M.L.

P.M.L. is caused by the JC virus, which is present in most people but lies dormant in the kidneys or lymph nodes. It is thought that Tysabri weakens the immune system, which, allows the virus to become active.

The Belgian researchers found that the JC virus was present in the blood, perhaps a precursor to entering the brain, two months before the patient was admitted to the hospital with symptoms of the disease.

A second paper, by doctors at Stanford and the University of California, San Francisco, reported on a patient who now appears to be recovering from P.M.L.

Biogen executives said in a letter to the medical journal that, taken together, those observations suggested it might be possible to monitor patients closely and then stop the drug if the virus is detected in the blood in time to avert serious consequences. Biogen is now analyzing blood samples from the other patients to see if they, too, had JC virus in their blood well before the onset of P.M.L. symptoms.

But Dr. Joseph R. Berger of the University of Kentucky, the co-author of an editorial in the medical journal, said, "We don't know if simply stopping the drug once the virus is observed is going to prevent development of the disease."

Dr. Berger, a consultant to Biogen and many of its competitors, said evidence from the papers suggested that the drug continues to have an effect up to three months after the last dose. Moreover, he said, there is no good treatment for P.M.L. Even if the disease is not fatal, patients can be left with problems. The patient in California is now at a rehabilitation center but still cannot walk, said Dr. Annette Langer-Gould of Stanford, an author of the paper.

Moreover, when Tysabri wore off three months after the last dose, the patient's immune system went into overdrive, causing severe inflammation that nearly killed him.

LINK....FREE REGISTRATION REQUIREDIf the fourth case of the normally extremely rare infection is confirmed, it would make it more difficult for the drug to return to the market, doctors and analysts said. The new case might indicate the drug is more dangerous than previously thought because it appears the fourth patient might have taken the drug for a substantially shorter time than the other three.

Mr. McGlynn of Elan said the patient with the new possible case was not someone who had participated in clinical trials of the drug, as the other three confirmed P.M.L. patients had done. That would suggest the person would have received only a few monthly doses at most, since the drug was not generally available before November.

"If this someone who got three or four doses that would be a major concern," said Dr. Patricia K. Coyle, a professor and the acting chairwoman of neurology at SUNY Stony Brook.

The first two patients had taken Tysabri, in combination with Avonex, another multiple sclerosis drug from Biogen for more than two years. The third patient, who had Crohn's disease, had received 8 doses of Tysabri over 18 months and had not taken Avonex

LINK"around the Feb. 28 announcement that the drugmaker was suspending sales of the multiple sclerosis drug Tysabri."

LINK: "In corporate news, Elan (down $3.88 to $3.10, Research) and Biogen Idec (down $3.78 to $34.57, Research) both sank after the companies said that a third patient taking their suspended multiple sclerosis drug Tysabri had contracted a rare neurological disease, making it unlikely the drug will return to the market anytime soon, if at all."

CLICK HERE FOR COMPLETE STORYElan Corporation, plc (NYSE: ELN) and Biogen Idec (NASDAQ: BIIB) announced today that their ongoing safety evaluation of TYSABRI(R) (natalizumab) has led to a previously diagnosed case of malignant astrocytoma being reassessed as progressive multifocal leukoencephalopathy (PML), in a patient in an open label Crohn's disease clinical trial.

The makers of the multiple sclerosis drug Tysabri said yesterday that a second patient who used the drug had been confirmed to be suffering from a rare but deadly brain infection.

CLICK TO READ MORE The confirmed diagnosis is likely to somewhat diminish the chances that the drug will be able to return to the market.The brain infection, called progressive multifocal leukoencephalopathy, or P.M.L., is extremely rare, so even one confirmed case raised alarms, officials of the companies have said. The confirmation of a second case is stronger evidence that the disease is linked to the drug.

The two patients were among 500 people in a trial who had received both Tysabri and Avonex, another Biogen multiple sclerosis drug, for more than two years.

Biogen and Elan reiterated yesterday that they had received no reports of P.M.L. in patients who received Tysabri alone. Avonex has been on the market for years and has never been associated with the condition when used alone.

The sudden withdrawal of the new multiple sclerosis drug Tysabri is a major blow to drug developers Biogen Idec and Elan Pharmaceuticals, both of which hoped to dramatically expand the market for such medications by as much as 30 percent.

LINK

BREAKING NEWS: FDA Issues Public Health Advisory on Tysabri, a New Drug for MS

LINK TO COMPLETE ARTICLE

"FDA worked with the company to make sure this information, even though preliminary, was given to physicians and patients as soon as possible and supports their decision to voluntarily suspend marketing as well as the use of the product in clinical trials.

At the same time, FDA continues to believe Tysabri offers great hope to MS patients," said Dr. Steven Galson, Acting Director, FDA's Center for Drug Evaluation and Research (CDER).

"Patients being treated with Tysabri should contact their physician to discuss appropriate alternative treatments while these reports are being evaluated," added Dr. Galson.

BREAKING NEWS: TYSABRI -SPECIAL WEBCAST AT 5:30 EST TONIGHT

'I WOULD LIKE TO THANK CHRIS UITHOVEN, PRESIDENT OF THE NATIONAL MULTIPLE SCLEROSIS SOCIETY, ARIZONA CHAPTER FOR THE FOLLOWING INFORMATION!" Stan Swartz, Publisher


This afternoon, March 1, 2005, at 5:30 EST, MS Learn Online will present a special webcast about the recent suspension of Tysabri.

Presenters include:

Dr. John Richert, Vice President of the Research and Clinical Programs Department of the National MS Society

Dr. Aaron Miller, Chief Medical Officer of the National MS Society and Medical Director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis in New York City

Dr. Al Sandrock, Vice President for Medical Research for Biogen IDEC.


We will address common concerns and questions such as:

• Why was Tysabri suspended?
• What is PML?
• Is PML due to Avonex, Tysabri, or the combination of both?
• Is PML related to MS? Should I be tested?
• Are clinical trials being stopped?
• What does the FDA have to say about this?

A written transcript of this webcast will be available on the MS Learn Online site by Thursday, March 3, 2005.


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Click here today at 5:30 p.m. EST to go to webcast. This program will be continuously available on our web site after 5:30 p.m., March 1, 2005.


For more general information about Tysabri, go to the FDA web site at http://www.fda.gov/cder/drug/infopage/
natalizumab/natalizumabQA_2_2005.htm.

DON'T MISS THIS TONIGHT

CLICK HERE - and look for the MS Learn Online announcement.

WE WOULD LIKE TO AGAIN - THANK CHRIS UITHOVEN, PRESIDENT OF THE NATIONAL MULTIPLE SCLEROSIS SOCIETY, ARIZONA CHAPTER FOR GIVING US THIS BREAKING NEWS TO ANNOUNCE ON OUR SITE AND IN OUR E-MAIL ALERTS

LIVE AUDIO CONFERENCE REGARDING SUSPENSION OF TYSABRI:

Biogen Idec and Elan will hold a webcast later today at 11.30am Eastern Standard Time (EST), 4:30 p.m. Greenwich Mean Time (GMT) to discuss their announcement of a voluntary suspension of Tysabri.

CLICK HERE FOR MORE INFORMATION: www.elan.com

Biogen and Elan suspend Tysabri!!!!!!!!!


CNN- [LINK]

The New York Times > Business > [LINK]

FDA Approves Tysabri: "Because of positive data from clinical trials, the FDA approved Tysabri—formerly called Antegren®—after only one year of study. Usually, two years of trials are required before approving a new drug.Trial results a 66% reduction in the relapse rate of MS symptoms in patients studied when compared with placebo."

[Tysabri] FDA NEW RELEASE: FDA has licensed a new biologic approach to treat patients with relapsing forms of multiple sclerosis (MS) to reduce the frequency of symptom flare-ups or exacerbations of the disease.FDA has licensed a new biologic approach to treat patients with relapsing forms of multiple sclerosis (MS) to reduce the frequency of symptom flare-ups or exacerbations of the disease.

[Tysabri] FDA APPROVAL LETTER

[Tysabri] Elan Corporation News Release: Biogen Idec (NASDAQ: BIIB) and Elan Corporation, plc (NYSE: ELN) announced today that the U.S. Food and Drug Administration (FDA) has approved TYSABRI(R) (natalizumab), formerly referred to as ANTEGREN(R), as treatment for relapsing forms of multiple sclerosis (MS) to reduce the frequency of clinical relapses.