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Biogen calls halt to its MS drug

Biogen Idec Inc. of Cambridge yesterday abruptly told doctors to stop using its new multiple sclerosis treatment, Tysabri, and halted shipments and clinical trials involving the drug after one patient who had taken the drug in trials died from a rare brain virus.

Another unidentified patient is believed to be infected with the virus, Biogen Idec officials said.

The move, made after lengthy talks with the Food and Drug Administration, stunned multiple sclerosis patients, who had flocked to the new drug as a potential breakthrough in treating the debilitating disease. Tysabri, approved by the FDA in late November, had already been used to treat more than 5,000 patients.

The withdrawal reflects the recent intense scrutiny of the drug industry and FDA from Congress over the agency's response to negative trial results, such as those that exposed risks posed by popular painkillers and antidepressants. But it also reflects the challenges faced by the industry and regulators, who must balance safety concerns and possible risks when new drugs show tremendous health benefits.

''People are pretty freaked out," said Art Mellor, president and chief executive of the Boston Cure Project for Multiple Sclerosis, a charity that funds MS research. ''They're less freaked out that 'Oh my God, this drug might have killed me' than 'Oh my God, this drug that may have helped me is going away.' This is very much a bummer."

One of those patients is Lissa Gifford, 45, of Watertown. ''Within three days of my first infusion I could feel my fingers and toes again," she said. ''My toes went off in 1986. Within the week, I swam for half a mile. Now, I go up and down the stairs, I go grocery shopping whenever I want to, I can put on mascara, I can stand on one foot."

Gifford said she had to give up her doctoral studies at Brandeis University when her symptoms became too severe. After trying mostother therapy available -- including Biogen Idec's other MS treatment, Avonex, and nontraditional treatments such as bee stings -- she said, ''This is absolutely the last drug for me. I just hope the FDA checks it out as quickly as possible."

In contrast to most earlier MS treatments, in which patients give themselves injections once or several times a week, Tysabri is administered as a monthly intravenous infusion at a doctor's office.

The surprise decision to halt marketing and prescribing of the drug came about 11 days after Biogen Idec learned of the viral infections. Investors were shocked. Biogen shares lost $28.63, or 42.6 percent of their value, closing at $38.65, the lowest level since January 2004.

Last year, Biogen Idec was the biggest gainer of any stock on the American Stock Exchange Biotechnology Index, up 81 percent, largely on the boost provided by the expected early approval for Tysabri.

Elan Pharmaceuticals PLC of Ireland, Biogen Idec's marketing and development partner on Tysabri, was hit even harder. Its American depositary shares dropped $18.90 to close at $8, a 70 percent loss.

Nearly $18 billion in shareholder equity was wiped out at both companies.

Executives made millions before dealing with FDA. D3.

Shares in Serono SA, a Swiss drug giant that markets a competing MS treatment called Rebif, soared 19 percent.

The decision to immediately suspend distribution and administration of Tysabri was a cautious approach that may have been influenced by the newly discovered risks associated with so-called cox-2 painkillers. In September, the pharmaceutical giant Merck & Co. pulled Vioxx off the market, citing a new study that linked the medication to an increased risk of heart attacks and strokes.

Similar questions were raised about two competing drugs, Celebrex and Bextra, made by Pfizer Inc. The FDA was criticized for not monitoring the health impacts more closely and accused of putting patients at risk.

Today, senators will explore weaknesses in the agency's drug-approval process in the first of two FDA hearings this week at the Senate Health Education Labor and Pensions Committee. Some senators have already criticized the agency as too close to the industry it regulates. Others are urging the creation of an independent office of drug safety that would track serious side effects, such as those that derailed Tysabri.

Multiple sclerosis is a progressive, degenerative disease of the central nervous system in which the body's immune system attacks the myelin, a sheath covering nerves, causing scarring, or sclerosis, and preventing the nerves from properly transmitting signals. The symptoms vary widely and can be as mild as weakness and tingling in the limbs to severe, disabling symptoms including paralysis, dementia, and blindness. Many patients suffer flare-ups followed by periods of partial relief from symptoms. It affects about 400,000 Americans and about 2.5 million people worldwide, according to the National Multiple Sclerosis Society.

Tysabri helps MS patients in a different way than most other treatments on the market. Tysabri works by blocking disease-fighting T cells from migrating to the brain and attacking healthy nerve tissue. Many patients who had seen their symptoms worsen with other drugs had eagerly anticipated Tysabri. Though it doesn't cure the disease, Tysabri was able in some patients to reduce symptoms resistant to current treatments.

Biogen was a leader in multiple sclerosis treatment well before its 2003 merger with Idec. Its drug Avonex, introduced in 1996, is one of several similar drugs known as interferons that have provided significant relief to some patients, although why the drugs worked largely remains a mystery.

Biogen grew into a big company, with annual sales of more than $1 billion, on the strength of Avonex.

Tysabri was discovered by a company later acquired by Elan, which teamed up with Biogen in 2002. Biogen leads development and marketing of Tysabri for MS, while Elan is developing the drug for other conditions, including rheumatoid arthritis. The companies split revenues.

Yesterday's suspension of Tysabri shipments, trials, and treatment is all the more startling because the drug seemed to be on an unstoppable winning streak. Biogen Idec conducted trials of Tysabri alone and in combination with Avonex. The interim results were so good that the company last year asked the FDA for approval a year ahead of schedule, with only a year of late-stage test results. The FDA gave the drug fast-track status so it would be reviewed quickly. In late November, it approved Tysabri to treat MS by itself and in combination with Avonex.

All went well until last month, when two undisclosed medical centers participating in long-term, post-approval trials of Tysabri reported independent cases of progressive multifocal leukoencephalopathy, or PML. It is a rare disease that works in a similar fashion to MS, attacking the myelin that covers nerves. But PML is an opportunistic infection, sometimes seen in AIDS patients and in others with compromised immune systems. Though there is no cure for PML, its progression can be slowed with anti-HIV medications. The relentless disease often proves fatal within four months.

The appearance of PML could be a signal that Tysabri compromises patients' immune systems. Both patients had been treated with Tysabri and Avonex together and were participating in studies of Tysabri's long-term effectiveness. Biogen Idec declined to identify the patients or specify where they were being treated.

Dr. Burt Adelman, Biogen Idec's executive vice president of development, said the reports came as a surprise. With extensive research into treatments affecting the immune system, Biogen Idec had looked closely for signs of opportunistic infections that can appear when the body's immune response is compromised. None had surfaced.

This week, Biogen Idec will convene a meeting of experts on PML to learn more about possible connections between Tysabri and the disease. It also plans to review brain-scan images from thousands of patients who participated in Tysabri's clinical trials, to look for warning signs of PML, and will ask doctors participating in trials to examine patients who have taken Tysabri, to see if they have any symptoms of the disease.

The company declined to predict when the drug might return to the market. About 3,000 patients took Tysabri during the drug's clinical trials.

Elan's officials were bolder. In a conference call with investors, Kelly Martin, Elan's president and chief executive, said it is ''very plausible" Tysabri will be back on the market this fall if there are no new cases of PML. He said the FDA ''unequivocably" wants the drug to be sold.

''It is not their intention to have this drug removed from the market," he said.

Alice Dembner and Diedtra Henderson of the Globe staff contributed to this report. Jeffrey Krasner can be reached at krasner@globe.com.

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