UPDATE 1-Biogen moves long-acting Avonex to final trial-CEO

By Deena Beasley

LOS ANGELES, Jan 7 (Reuters) - Biogen Idec Inc (BIIB.O: Quote, Profile, Research) has moved a long-acting version of its multiple sclerosis drug, Avonex, directly into trials designed to meet requirements for regulatory approval, the company's chief executive said on Wednesday.

CEO Jim Mullen said during an investor conference held in New York that the company has completed Phase 1 trials and will study dosing the drug once every two weeks as well as once monthly.

"I think we've got a good chance of similar efficacy as interferons," he said.

Patients in the trials will be treated for one year with the injectable drug and full results will likely be available in two years, Mullen added.

Avonex, with sales of $573 million in the third quarter of 2008, is the leading drug for multiple sclerosis, an autoimmune disease in which the body mistakenly attacks the fatty myelin coating surrounding nerve cells.

Biogen, along with marketing partner Elan Corp Plc (ELN.I: Quote, Profile, Research), also sells MS drug Tysabri, which was taken off the market after its 2004 introduction when it was linked to a potentially fatal brain infection, but reintroduced beginning in 2006 because there were so few good options for patients with MS.

Mullen said investors continue to underestimate the newer drug's sales potential: "We have a much more bullish view on Tysabri than the Street does."

"We've got a 40 share of the overall MS market, which could easily go to 50," the CEO said.

He said other discrepancies between Biogen's outlook and that of Wall Street include the company's "more bullish view on the sustainability of Avonex," growth potential for the franchise surrounding non-Hodgkin's lymphoma drug Rituxan, and additional opportunities for trimming costs.

Mullen said Biogen will no longer report new cases of progressive multifocal leukoencephalopathy, the brain infection associated with Tysabri, through filings with securities regulators, but will instead issue weekly updates on its Web site. (Reporting by Deena Beasley; Editing by Andre Grenon and Matthew Lewis)

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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.

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.

Tysabri Product Use Disclaimer

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.

Biogen, Elan Report Brain Infection in Tysabri Users

By Tom Randall

July 31 (Bloomberg) -- Biogen Idec Inc. and Elan Corp. reported two confirmed cases of a deadly brain infection in patients taking the multiple sclerosis drug Tysabri, the first since the drug was reintroduced in the U.S. in 2006.

The report sent shares of both companies tumbling. The two patients were in the European Union, Biogen said today in a regulatory filing. The cases of the disease, progressive multifocal leukoencephalopathy, were confirmed this week, according to the company's statement.

Biogen and Elan voluntarily pulled the drug from the market in February 2005 after three patients unexpectedly contracted the disease, which caused two deaths. Tysabri was reintroduced in July 2006 in the U.S. and sold for the first time in the EU at the same time. One patient had been taking the drug for 17 months and the other took it for 14 months, Biogen said.

``This is going to be fairly disruptive to sales in the United States,'' said Mark J. Schoenebaum, an analyst with Deutsche Bank Securities in New York, by telephone. ``There is a real fear of the unknown here, and I think some patients and physicians are going to take a drug holiday'' until the company discloses more details.

More than 31,800 multiple sclerosis patients use Tysabri, Biogen spokeswoman Naomi Aoki said. About 14,000 patients have taken Tysabri for more than a year, and 6,500 patients have taken it for 18 months or longer.

Anticipated Cases

``We've said ever since the reintroduction that we anticipate seeing additional cases,'' Aoki said today in a telephone interview. ``Withdrawing the drug is not under consideration.''

The condition was included in the prescribing information on the drug as a possible side effect in 1 of every 1,000 patients taking the drug, Aoki said. One patient is clinically stable and is at home, Biogen said. The other patient is hospitalized.

The shares of Biogen, which is based in Cambridge, Massachusetts, fell by $14.06, or 20 percent, to $55.60 at 7:20 p.m. New York time, after the close of regular trading on the Nasdaq Stock Market. American depositary receipts of Elan, which is based in Dublin, fell by $7.98, or 39 percent, to $12.07. Each receipt equals one ordinary share.

``We expect the stock to open sharply down on Friday, but would not be buyers as we think investor sentiment could continue to weaken,'' Schoenebaum said in a note.

Goal of 100,000 Patients

On July 22, Biogen reported second-quarter net income rose 11 percent to $207 million on sales of Tysabri, its fastest- growing treatment. Biogen has estimated 100,000 patients will be taking Tysabri by 2010, a goal critical to the company's future growth, Thomas Weisel analyst Ian Somaiya said in a note to clients at the time.

Tysabri was approved in the U.S. in January to treat Crohn's disease, an inflammatory intestine and bowel disorder.

Shares of Elan, Ireland's biggest drugmaker, already were battered this week after Wyeth and Elan's experimental treatment for Alzheimer's disease, bapineuzumab, was linked in a study to a brain-swelling side effect.

To contact the reporters on this story: Tom Randall in New York at trandall6@bloomberg.net
Last Updated: July 31, 2008 19:29 EDT

Elan shares plummet on new MS drug concerns

Saturday September 15 2007


Shares in drugmaker Elan plummeted yesterday following fears that a patient taking the company's multiple sclerosis drug Tysabri had a virus called JC -- the precursor to the often fatal disease which caused the suspension of the drug's sales back in 2005.

The shares finished yesterday down 7.2pc at €13.13 having fallen over 9pc earlier, shadowing a drop in the US. The shares were at $18.86 in early US trade but had fallen to $18 earlier from a close of $19.48 on Thursday night.

Analysts said yesterday, there are growing concerns that the US Federal Drug Administration (FDA) has received an adverse event report from a doctor who had detected the JC virus which is a precursor to progressive multifocal leukoencephalopathy (PML).

Although 80pc of the population have antibodies to the virus, if a person has a weak immune system the JC virus can cross over the blood/brain barrier into the brain. The virus persists in the kidney.

Back in 2005, Elan shares plummeted by 70pc on the Dublin Stock Exchange after it and its partner Biogen said they were suspending sales of their much-heralded multiple sclerosis drug Tysabri.

The move followed the news that one patient died of PML, a rare and often fatal disease of the central nervous system known as an opportunistic infection, after being treated with Tysabri in combination with Biogen's MS drug Avonex.

This latest patient, however, has not been confirmed as having the PML virus. Elan said that it has no new confirmed cases of PML.

It added that it gave the FDA a full safety update at the end of July..

Analysts said yesterday that the share slump was probably a result of panic selling especially as no new cases of PML have been reported.

"Previous adverse reports when Tysabri was under a market suspension proved to be unfounded," said one analyst who did not wish to be named.

In 2005, the two companies said there was one fatal, confirmed case and one suspected case of PML.

The companies also suspended dosing in all clinical trials of the drug. The action was been taken in consultation with the US FDA at the time.

Earlier this week, Tysabri received backing from a Scottish health watchdog for its MS drug.

The Scottish Medicines Consortium (SMC) today advised the use of Elan's and partner Biogen's drug Tysabri in people with active relapsing remitting multiple sclerosis.

All NHS Health Boards in Scotland are now obliged to consider the SMC's advice and ensure that Tysabri is made available to meet patients' needs.