Two New Cases of PML in MS Patients Taking Tysabri

UPDATE FROM NATIONAL MS SOCIETY:

Aug 01, 2008

Two New Cases of PML Develop in People with MS Taking Tysabri

Biogen Idec and Elan Pharmaceuticals informed drug regulatory authorities about two new confirmed cases of PML in individuals who were taking Tysabri® (natalizumab) as a monotherapy (not in combination with other therapies). PML (progressive multifocal leukoencephalopathy) is a viral infection of the brain that usually leads to death or severe disability. Although FDA prescribing information includes a black box warning about the risk of PML, the three previous cases of PML that occurred in the context of clinical trials were in patients who had taken Tysabri in association with other immune-modulating or immune-suppressing medications.

Details: The companies held a conference call for prescribers and investors to provide details about the two cases, both of which occurred in European males. One had received Tysabri as a first line therapy because of the aggressive nature of his disease, and had been on Tysabri alone for 17 months before developing a slowly progressive focal twitching and weakness in one arm. Brain MRI showed a non-typical lesion but his spinal fluid was negative for JC virus until it was done a second time. He received five courses of plasma exchange and is currently stable and at home.The second case has been reported to be a male who had received immune-suppressing and immune-modulating therapies in the past. He used Tysabri alone for 14 months before developing weakness on one side of the body. Despite treatment with steroids his symptoms progressed and included cognitive changes. His MRI was not typical for MS, and spinal fluid was positive for JC virus. He is reported to be hospitalized and is slated to receive plasma exchange therapy.

Background: Tysabri is a laboratory-produced monoclonal antibody. It is designed to hamper movement of potentially damaging immune cells from the bloodstream, across the "blood-brain barrier" into the brain and spinal cord. It has been shown to be effective in reducing the risk of disability progression and exacerbations (relapses).

In the United States, the drug is available only through a risk management program called TOUCH, and is only available through doctors and infusion sites enrolled in the program. The program is designed to monitor patients for possible signs of PML and other serious opportunistic infections. Separate risk management plans are also in place in individual countries in Europe.

The companies recently reported that nearly 32,000 patients have been dosed with Tysabri. Of those, nearly 14,000 have been on the drug for at least 12 months, and 6,600 have been on the drug for at least 18 months. Up to this time there have been no previous confirmed cases of PML in patients using the drug as monotherapy.

Recent, small-scale studies supported by Biogen Idec have investigated the use of plasma exchange, a blood-cleansing treatment, to clear the bloodstream of Tysabri in the event of PML, for which there is no established therapy. The studies suggested that plasma exchange could indeed clear much of the drug from a person's bloodstream, but it was not possible to determine experimentally whether that would lead to a reduction of PML symptoms.

Comment: These incidents of PML are unfortunate and disappointing, and we hope for the best possible outcomes for these individuals and their families. However, their occurrence is within range of the predicted frequency of PML cases, estimated by a published report and by the FDA, of approximately 1 in 1,000 people taking the drug. "We are encouraged that the risk management plans in place for early surveillance, such as the TOUCH program in the U.S., are doing the intended job of identifying possible cases of PML early so that patients can be treated quickly," said John R. Richert, MD, executive vice president of research and clinical programs at the National MS Society . "It will be important to observe whether plasma exchange therapy in these new cases will have an ameliorating effect on their PML."

These incidents highlight the need for individuals taking Tysabri to be sensitive to any occurrence of new, unusual symptoms and to contact their prescribing physician or infusion nurse immediately if they occur. Signs of PML may include any new or worsening neurological symptoms such as any changes in thinking, eyesight, balance, strength and other symptoms.

Tysabri is a registered trademark of Biogen Idec and Elan.

The National MS Society is proud to be a source of information about MS. Our comments are based on professional advice, published experience and expert opinion, but do not represent individual therapeutic recommendation or prescription. For specific information and advice, consult your personal physician.

Biogen and Elan report Tysabri brain disease cases

By Deena Beasley and Bill Berkrot
Reuters, published August 1, 2008

LOS ANGELES/NEW YORK: Biogen Idec and Elan have notified regulators of two new cases of a potentially deadly brain disease in multiple sclerosis (MS) patients being treated with Tysabri.

Biogen shares dropped about 23 percent in after-hours trading, while Elan's shares fell 45 percent in New York.

"This is going to have very broad, very wide ramifications for the commercial prospects of the drug because there's just a lot of uncertainty here," said Cowen & Co analyst Eric Schmidt.

Tysabri, co-marketed by Ireland's Elan and Cambridge, Massachusetts-based Biogen, was withdrawn from the market in 2005 after three patients developed the brain infection known as progressive multifocal leukoencephalopathy (PML).

The drug returned to the market in 2006 with warnings after the U.S. Food and Drug Administration decided MS patients willing to accept the risks should be able to have access to the drug's potential benefits.

The two new PML patients, one of whom is hospitalized, are in the European Union, the companies said.

More cases are likely and physicians are likely to reduce the number of patients they start on the drug as they are reminded of long-term potential safety issues, Morgan Stanley analyst Steven Harr said in a research note.

Elan and Biogen said more than 31,800 patients were being treated with Tysabri as of the end of June and second-quarter sales totalled $200 million (100 million pounds).

"We've said all along, and the FDA has also stated and it's clearly outlined in our label that we expect to see additional cases of PML," Biogen spokeswoman Naomi Aoki said. "These are the first cases we've seen since the reintroduction in the U.S. and approval in Europe two years ago."

She said the company believes that heightened clinical vigilance has been the best way to monitor for PML and that heightened vigilance was critical in identifying these cases.

Schmidt said, the "key fear factor in the market place is going to be what happens when you treat beyond two, two and a half years ... Nobody knows the answer and that's kind of scary."

"I think you'll see a general pause in the market place, especially in the U.S., where safety has become more of a lightning rod issue, in part driven by the litigious nature of our society," the analyst said.

Tysabri also won U.S. approval this year to treat adults with moderate to severe Crohn's disease who have had a poor response to, or cannot take, other therapies.

Shares of Biogen, which closed at $69.76 on Nasdaq, fell to $53.68 after hours, while shares of Elan, which closed at $20.05 on the New York Stock Exchange, were trading at $11.00.

Elan's shares had already lost one-third of their value on Wednesday when investors sold the stock after disappointing data on an experimental Alzheimer's drug Elan is developing with Wyeth.

Biogen and Elan have a scheduled a conference call with analysts and investors for Friday morning.

(Reporting by Deena Beasley and Bill Berkrot; editing by Jeffrey Benkoe and Carol Bishopric)

Biogen Idec and Elan Corporation, plc
Host Conference Call For Investment Community

Date: Friday, August 1, 2008
Time: 8:30a.m. ET
Length: 1 hour

Listen to Webcast here


Below is the report filed with the SEC on July 31, 2008.

Item 8.01 Other Events.

On July 31, 2008, Biogen Idec Inc. and Elan Corporation, plc notified relevant regulatory agencies of two confirmed cases of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients treated with TYSABRI in the commercial setting. Additional information about these cases is set forth below.

Case 1

	•		On July 30, 2008, following a period of clinical evaluation, Biogen Idec received confirmation of a diagnosis of PML in a MS patient in the European Union (EU).
	•		The diagnosis was made based upon the detection of JC Virus (JCV) DNA in the cerebrospinal fluid (CSF) in the setting of clinical signs, symptoms and magnetic resonance imaging (MRI) findings consistent with the diagnosis of PML.
	•		As reported to the company on July 31, 2008, the patient remains clinically stable and ambulatory at home.
	•		Background:

	-		Patient in EU with aggressive MS who was naïve to prior disease modifying therapy;
	-		TYSABRI monotherapy for approximately 17 months;
	-		Clinical vigilance led to early identification of signs and symptoms of possible PML and medical work-up which included MRI scanning and CSF testing, but PML was not confirmed at that time;
	-		However, given continued clinical suspicion by treating physician plasma exchange was initiated as outpatient;
	-		Subsequent testing of CSF detected JCV DNA which was reported to the company on July 30, 2008;
	-		It was then determined by PML experts that the latest CSF results together with the clinical history, physical findings, and MRI results are consistent with the diagnosis of PML.

Case 2

	•		On July 31, 2008, Biogen Idec was notified of a diagnosis of PML in a second MS patient in the EU.
	•		The diagnosis was made based upon the detection of JCV DNA in the CSF in the setting of clinical signs, symptoms, and MRI findings consistent with the diagnosis of PML.
	•		As reported to the company on July 31, 2008 the patient is currently hospitalized.
	•		Background:

	-		Patient in EU with MS with a history of prior disease modifying therapies including azathioprine and beta-interferons;
	-		TYSABRI monotherapy for approximately 14 months;
	-		Evaluation for possible PML included MRI scanning and CSF testing;
	-		CSF testing detected JCV DNA, which was reported to the company on July 31, 2008;
	-		The CSF results together with the clinical history, physical findings, and MRI results are consistent with the diagnosis of PML.