Tysabri PML Cases Cause European Regulators to Recommend Stronger Warnings

September 29th, 2008

The European Medicines Agency, an advisory body for drug regulators in Europe, recommended last week that the warning label for the multiple-sclerosis drug Tyasabri be updated following new reports of users developing a rare brain disease known as PML, or progressive multifocal leukoencephalopathy.

Tysabri (natalizumab) is an intravenous injection given every 28 days to treat Crohn’s Disease or multiple sclerosis (MS). It has been shown to prevent relapse, cognitive decline and vision loss which could be associated with multiple sclerosis.

Shortly after Tysabri was introduced in 2004, it was associated with side effects that could lead to PML, which is a potentially fatal brain infection. After three cases of PML resulted in two deaths, a Tysabri recall was issued in 2005, and the drug was re-introduced the next year with stricter guidelines for usage and more prominent warnings about the possible Tysabri PML side effects.

European and American drug regulators have been re-examing the risk of progressive multifocal leukoencephalopathy in recent months, after new reports of PML among Tysabri users surfaced in July 2008. According to filings with the SEC, the drugs makers, Biogen Idec and Elan Corporation, identified two PML cases in Europe, which were the first new diagnosed Tysabria PML cases since 2006.

On September 25, 2008, the European Medicines Agency’s Committee for Medical Products for Human Use (CHMP) called for drug regulators to strengthen the Tysabri progressive multifocal leukoencephalopathy warnings in Europe. They recommended that the drug’s prescription information be updated and strengthened to highlight the potential Tysabri side effects for patients with relapsing-remitting multiple sclerosis (MS).

The European regulatory committee did not call for a Tysabri recall, as they indicated that the benefits of the drug still do outweigh the risks. However, in light of these new PML cases, they felt that the current warnings in Europe need to be strengthened to raise awareness about the risk of the brain disease from Tysabri.

In August 2008, the FDA issued a MedWatch Alert regarding the new reports of PML associate with Tysabri. They indicated that the prescribing information in the United States would be revised to include information for prescribers and patients about the cases of PML that occurred among patients taking Tysabri as a monotherapy. The U.S. drug regulators also recommended that doctors should monitor their patients for signs and symptoms of PML.

that they are investigating the reports to determine what, if any, regulatory actions are necessary regarding the Tysabri side effects.

Progressive multifocal leukoencephalopathy is a rare viral infection which causes inflammation at multiple locations in the brain, leading to progressive brain damage. Symptoms could include loss of vision, impaired speech, paralysis, cognitive decline and weakness. There is no known cure for PML, but the disease can sometimes be slowed or stopped by reducing immunosuppression. In many cases the brain infection is fatal.

EMEA says Elan and Biogen's Tysabri should carry liver injury warnings

03.20.08, 12:44 PM ET

LONDON (Thomson Financial) - The European Medicines Agency EMEA has announced the labels for Elan and Biogen's Tysabri should include warnings about liver injury on its product information.

The EMEA's Committee for Medicinal Products for Human Use has requested that Elan (nyse: ELN - news - people ), the marketing authorisation holder for Tysabri, submits a variation to the marketing authorisation to implement these changes.

Last month Elan and Biogen announced some patients suffered liver injury after taking the multiple sclerosis treatment.

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Elan and Biogen Idec Preparing to Appeal Ruling on European Application for Natalizumab for the Treatment of Crohn's Disease

DUBLIN, Ireland & ZUG, Switzerland--(BUSINESS WIRE)--Jul 19, 2007 - Elan Corporation, plc (NYSE: ELN) and Biogen Idec (NASDAQ: BIIB) announced today that they have been informed by the European Medicines Agency (EMEA) that the Committee for Medicinal Products for Human Use (CHMP) has adopted a negative opinion on the marketing application for the use of natalizumab in patients with Crohn's disease. In accordance with European regulations, Elan and Biogen Idec plan to apply for a re-examination of the negative opinion through the appeal procedure. A decision on the appeal is expected by 1Q 2008.

"Without natalizumab, European patients with severely active disease who failed other therapies and who are suffering from continuous symptoms may be offered surgery, with its potential complications, intravenous nutritional therapies or clinical trials with unproven experimental agents, depending upon on the patients' condition," said Professor Jean-Frederick Colombel, University of Lille. "There is a need for new therapies for this very difficult disease."


An application for approval of TYSABRI(R) (natalizumab) for treatment of moderate to severe Crohn's disease was filed in the US on December 15, 2006. The FDA is holding an advisory committee to discuss the application on July 31, 2007.

About Crohn's Disease

Approximately one million people worldwide have Crohn's disease, a chronic and progressive inflammatory disease of the gastrointestinal tract, which commonly affects both men and women.

The disease usually causes diarrhea and crampy abdominal pain, often associated with fever, and at times rectal bleeding. Loss of appetite and weight loss also may occur. Complications include narrowing of the intestine, obstruction, abscesses, and fistulas (abnormal channels connecting the intestine and other organs, including the skin), and malnutrition. Most patients eventually require surgery, which has both risks and potential short- and long-term complications.

Crohn's disease can have a devastating impact on the lifestyle of patients, many of whom are young and active. Currently there is no medical or surgical cure for Crohn's disease. Many patients fail to respond to current therapies, including biological therapies such as agents that inhibit tumor necrosis factor alpha (TNF-alpha). Due to this failure of current therapies in CD, therapies that have novel biological targets are required.

About TYSABRI(R) (natalizumab)

TYSABRI is a treatment approved for relapsing forms of multiple sclerosis (MS) in the US and relapsing-remitting MS in the European Union. According to data that have been published in the New England Journal of Medicine, after two years, TYSABRI treatment led to a 68% relative reduction (pless than0.001) in the annualized relapse rate compared to placebo and reduced the relative risk of disability progression by 42-54% (pless than0.001).

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

TYSABRI is approved in the United States, European Union, Switzerland, Canada, Australia and Israel. TYSABRI was discovered by Elan and is co-developed with Biogen Idec.

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

About Elan

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

About Biogen Idec

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

Safe Harbor/Forward Looking Statements

This press release contains forward-looking statements regarding TYSABRI. The commercial potential and regulatory path forward of TYSABRI are subject to a number of risks and uncertainties. Factors which could cause actual results to differ materially from the companies' current expectations include the risk that concerns may arise from additional data or analysis or that the companies may encounter other unexpected delays or hurdles. There is also no assurance that the companies will be able to obtain approval for TYSABRI as a treatment for Crohn's disease. Drug development and commercialization involves a high degree of risk. For more detailed information on the risks and uncertainties associated with the companies' drug development and other activities, see the periodic reports that Biogen Idec and Elan have filed with the Securities and Exchange Commission. The companies assume no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

Contact

Media:
Biogen Idec
Jose Juves, +41 41 3921860
Amy Reilly, +1 617-914-6524
or
Elan
Elizabeth Headon, +353 1 498 0300
Matt Dallas, +1 212-850-5664
or
Investor:
Biogen Idec
Eric Hoffman, +1 617-679-2812
or
Elan
Chris Burns, +353 1 709 4444/+1 800 252 3526