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U.S. Panel Backs Return for Withdrawn Drug Patients and Doctors Would Be Left to Judge If Gains Outweigh Risk for MS Sufferers

Posted on: Friday, 10 March 2006, 09:00 CST

By Andrew Pollack

A U.S. federal advisory panel has unanimously recommended that the multiple sclerosis drug Tysabri, which was withdrawn about a year ago for causing a deadly brain disease, be returned to the market.

In making its decision, the scientists and doctors advising the U.S. Food and Drug Administration said Wednesday, in effect, that patients and their physicians should have the right to decide whether the considerable benefits the drug offers outweigh risks that can perhaps be reduced but not totally avoided.

If the agency goes along with the recommendation, as it is expected to do by the end of the month, the approval would be only the second instance of a drug being returned to the market after having been withdrawn for safety reasons. The first, in 2002, was Lotronex from GlaxoSmithKline, for irritable bowel syndrome.

The decision is a victory for multiple sclerosis patients, about two dozen of whom pleaded at the meeting, some tearfully, for the return of the drug they called their best or only hope.

The committee's vote is also a victory for the drug's developers, Biogen Idec and Elan, which lost substantial market value when Tysabri was withdrawn from the market in February 2005, only three months after it was approved.

At that time few analysts thought the drug would return to the market as quickly as it apparently will.

The meeting "was a very moving two days," Dr. Burt Adelman, Biogen's executive vice president for development, said during an interview. He said the vote supported Biogen's view "that this is an important therapy and, although there are risks, patients should be able to choose."

Trading of both companies' shares was halted Tuesday and most of Wednesday. Shares in Elan, which is based in Dublin, jumped 2.45, or 21.68 percent, to 13.75 in morning trading Thursday on the Dublin exchange. Shares of Biogen, which is based in Cambridge, Massachusetts, closed $4.10, or 9 percent, higher Wednesday at $41.60

Still, most analysts say they no longer believe that Tysabri, also called natalizumab, will be a blockbuster.

Before the drug was withdrawn, some had projected annual sales would reach $2 billion or more. Now estimates are generally for several hundred million dollars.

"I think it's going to be a relatively slow relaunch, mainly because we just heard two full days of discussion as to all the limitations that have to be put in place to even allow the drug to come back," said Joel Sendek, a biotechnology analyst at Lazard. He estimates that sales will reach $48 million this year and $216 million in 2009

Three people who took Tysabri in clinical trials, or about one in 1,000, developed progressive multifocal leukoencephalopathy, or PML, a rare brain disease caused by a virus. Two of the three patients died, and the other was severely disabled.

The issue confronting the advisory panel, which met in Gaithersburg, Maryland, was that there is no good way to predict who would get the brain disease, which has no proven treatment.

Biogen executives said that if doctors rigorously monitor patients, they might detect the brain disease early enough to stop giving Tysabri and avoid death or disability. But agency officials and advisory panel members said it was far from certain that this could be done, especially since PML could easily be mistaken for multiple sclerosis itself.

"It is likely there will be cases of PML," the committee's chairman, Dr. Karl Kieburtz of the University of Rochester, said at the conclusion of the meeting. "It is likely there will be deaths from it."

Still, the decision to return the drug to the market seemed relatively easy for the panel. More of its time was spent discussing restrictions on use of the drug.

The committee said forcefully that Tysabri should not be used along with other multiple sclerosis drugs, even in clinical trials, because it might increase the risk of PML.

That means that sales of Tysabri might eat into sales of Biogen's other multiple sclerosis drug, Avonex, rather than being used alongside it.

The committee voted, 7 to 5, that the drug could be used as an initial therapy, rather than only in cases where one or more other drugs had been tried without success.

Under the plan, all patients getting the drug will be entered in a registry. They and their doctors will have to sign forms acknowledging the risk.

Biogen had proposed making the registry voluntary but the agency's staff objected.

Drugs will be distributed directly to authorized infusion centers.

Before each monthly infusion, a nurse will go through a checklist with patients to make sure they have no new symptoms that could indicate that they had developed PML. Some panel members said they thought that patients might try and cover up symptoms to keep getting Tysabri.

Some pharmaceutical executives say that the agency has become tougher on drug approvals in response to criticism that it has been lax on safety. The Tysabri decision could indicate a move toward more leniency.

But Dr. Robert Temple, director of medical policy in the agency's drug division, said that the decision was "consistent with what we've done before" because "the disease in question is a devastating disease."

About 400,000 Americans have multiple sclerosis, which can cause paralysis, blurred vision and other problems. Experts say tens of thousands of them are not helped by existing drugs.

In separate clinical tests using placebos, Tysabri did better in preventing relapses than did older drugs. That suggests that Tysabri is more effective than the older drugs, though proof of that would require testing it directly against the other drugs.

Still, some of the patients and their family members who testified at the meeting swore by the drug.

"Without Tysabri, she is at greater risk of ending up in a wheelchair and becoming a cognitive shell of the woman she once was," David Miller, who teaches business ethics at Yale Divinity School, said of his wife, Karen, who has multiple sclerosis.

Source: International Herald Tribune

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