Europe assessing Tysabri brain disease reports

14 August 2008
Europe’s medicines agency yesterday said it is currently in the process of assessing the two additional reports of the rare brain disease progressive multifocal leukoencephalopathy in multiple sclerosis patients receiving Elan Pharma’s Tysabri (natalizumab).

The two cases reported at the end of July occurred in patients who had been receiving Tysabri for more than 12 months, but renewed old fears for investors and the firm’s share price – along with that of its US partner Biogen Idec – sank on the news. The Ireland-based firm crashed almost 75% - reflecting the sensitivity and importance of the medicine to its future prospects, though it was also impacted by concerns over its Alzheimer’s disease drug bapineuzumab being developed with Wyeth.

The agency has also asked Elan to provide any additional information it may have, at which point its scientific advisory panel will decide whether the medicine’s product labeling needs updating. Tysabri has been under intense scrutiny since it was reintroduced in the USA and approved in Europe two years ago – and these are the first new cases to surface since that time. It was originally withdrawn from the market in 2005 after three patients developed PML, but following its reintroduction has gone on to be a big earner – pulling in some $200 million in the second quarter of this year alone. Almost 32,000 patients were receiving Tysabri as of the end of June.

Most analysts do seem to remain convinced of the value of Tysabri – certainly the firms do not intend to withdraw the drug again, stressing the stringent safety monitoring programme in place.

Icahn takes stake in Biogen on Tysabri woes
And rather than backing off from the stock, maverick investor Carl Icahn has seen the dip in Biogen’s value as an opportunity to snap up some cut-price shares – increasing his stake in the company to 6% from 4.3%. All eyes are on his movements: earlier on this year he criticised the board for not looking hard enough to find a buyer as well as its decision to take down the ‘for sale’ sign in December last year month after no serious offers were made. He could be gearing up to push for another sale.

Biogen, Elan stand by MS drug after illnesses

The Associated Press
Published: August 1, 2008


NEW YORK: Biogen Idec Inc. and Elan Corp. defended their multiple sclerosis drug Tysabri on Friday after reporting two new cases of a potentially fatal side effect, saying the treatment is still worth the risk to patients.

There are no plans to pull the drug off the market, and the company said its current monitoring program for cases of a rare but sometimes fatal brain disorder is adequate.

The announcement of two new cases of the rare viral infection called progressive multifocal leukoencephalopathy, or PML, sent shares for both companies plummeting and reignited already simmering concerns about the drug's sales potential. It was pulled from the market in 2005 after being linked to the rare brain disease but was reintroduced under restricted sales conditions in mid-2006.

"These cases underscore the importance of continued clinical vigilance so PML can be discovered and managed appropriately," said Dr. Cecil B. Pickett, president of research and development at Biogen.

He and several other executives tried to allay concerns over additional cases during a conference call with financial investors and analysts Friday morning. The company said it would also hold calls with several physician and patient groups.

The risks associated with the drug are clearly labeled, the company said, and all patients are not only notified but have to sign a waiver acknowledging the risks. PML almost always occurs in people with a severe immune deficiency, as is the case with most patients taking Tysabri.

Multiple sclerosis is an autoimmune disorder that results in physical and neurological damage.

There are about 32,000 patients on Tysabri worldwide, with 17,800 in the U.S., the company said. It would not comment on its financial outlook, but did say future cases of Tysabri were anticipated and factored into the goal of eventually getting the drug to 100,000 patients worldwide.

The companies maintain the drug still has a favorable risk-reward profile, meaning it is more helpful than hurtful, and monitoring programs are set up in the U.S. and Europe to catch any potential cases of PML early. Those systems rely on physicians to test for the condition if they start to see symptoms. Biogen and Elan would not comment the number of suspected cases, only confirmed cases.

Both new cases came out of European, with the first patient having been on Tysabri for 17 months. Another, who is still hospitalized, had been on Tysabri for 14 months. Still, the company said it can count about 6,600 patients on the drug for about 18 months now, reinforcing its stance that the treatment is worth the risk.

Food and Drug Administration officials could not immediately be reached for comment as of Friday morning.

The broader market, meanwhile, remains concerned over the impact on sales, which nearly tripled to $200 million during the second-quarter. The treatments costs about $30,000 per year.

"We do not believe that Tysabri will be withdrawn, based on this data, but it is likely to spook investors as the true rate of PML in Tysabri monotherapy is unknown," Goldman Sachs analyst Stephen McGarry said in a note to Elan investors.

Shares of Cambridge, Massachusetts-based Biogen fell to $50.28, their lowest point in more than a year, while shares of Ireland-based Elan fell to $10.67, their lowest point in nearly three years.

Study Highlights Disease Rebound Effects From Tysabri

FDAnews Drug Daily Bulletin
Sept. 24, 2007 | Vol. 4 No. 187

Patients with multiple sclerosis (MS) treated with Biogen Idec/Elan’s Tysabri may experience significant increases in disease activity after they stop using the drug, according to a study published in the online edition of Neurology.

According to study author Machteld Vellinga, a physician with the VU University Medical Center in Amsterdam, data from 23 patients who participated in registrational studies for Tysabri (natalizumab) in MS suggest that subjects developed new and enlarging T2 lesions following discontinuation of the treatment, an effect known as rebound. It appeared only to occur in patients exposed to the product for a short period of time.

The VU University Medical Center was a clinical trial site used during studies for the drug.

In response to the study, Biogen said it was not planning to study this issue further as clinical studies for Tysabri did not show evidence of disease rebound upon discontinuation of the drug.