A multiple sclerosis drug pulled from the market a year ago because of a rare but life-threatening side effect is on track to return — but with some strong restrictions on how it’s used.
Advisers to the Food and Drug Administration unanimously recommended Wednesday that the government let Tysabri’s manufacturers resume sales — but only to patients enrolled in a mandatory registry designed to track, if not minimize, the risk of a rare brain infection linked to the drug.
The FDA usually follows its advisers’ recommendations, and agency drug chief Dr. Robert Temple signaled it would do so with Tysabri.
"Devastating diseases often are treated by drugs that have problems of their own," Temple noted.
But he cautioned that deciding to take Tysabri would be "a tough decision," because as many as one in every 1,000 users might get the brain infection called progressive multifocal leukoencephalopathy, or PML. Perhaps more troubling, there’s no evidence that early detection of PML improves chances of survival.
"It may not kill you all the time, but it doesn’t leave you in very good shape," Temple warned. "I think our major objective will be to explain as clearly as possible to people the nature of the risk and its severity."
The move delighted patients who had clamored for a second chance at Tysabri because, while not a cure, it does work differently than standard treatments for nerve-damaging multiple sclerosis.
"We have our hope back," said Christy Cooksey-Dressell, who told FDA’s advisers how her mother, Janet Dressell, improved so much after a single Tysabri dose that she abandoned her walker — but now, 13 months later, is deteriorating badly again.
Only one other prescription drug, the irritable bowel treatment Lotronex, has ever returned to the market after being pulled because of dangerous side effects.
Tysabri’s manufacturers voluntarily stopped sales last year, only four months after FDA initially approved the drug, because three users were diagnosed with PML. Two of them died.
Now, calling the risk remote and the drug’s promise great, manufacturers Biogen Idec and Elan Corp. want to resume sales, and pledged Wednesday to work closely with the FDA on a risk-management program.
Multiple sclerosis afflicts about 350,000 Americans. The cause is unknown and there is no cure. The most common form causes periodic flare-ups of symptoms, which include trouble seeing and walking.
Recently published studies found that Tysabri cut the rate of relapse by as much as two-thirds, and reduced the number of people whose MS got worse. It appears to work by blocking destructive immune cells leaving the bloodstream and entering the brain, where they can inflame and damage nerves.
PML, the apparent side effect, is caused by a common virus that usually lies dormant. When it does cause disease, the most common victims are people with very weak immune systems, such as AIDS patients.
The question for would-be Tysabri users is how big a risk PML really poses. The one-in-1,000 risk that Temple cited could be higher, depending on the overall health of Tysabri users and how long they take the drug — or it might ultimately turn out to be lower.
Dr. Karl Kieburtz of the University of Rochester, who chaired the FDA advisory committee, cautioned that there are complicating factors: Clinical trials of Tysabri have included fairly young people whose MS wasn’t too severe. And PML’s symptoms are hard to distinguish from those of an MS relapse, because the two diseases both attack the coating of nerve cells.
All those unknowns helped push FDA’s advisers to call for fairly stringent restrictions, Kieburtz said. In addition to a mandatory patient registry, the drug should be administered only in specially designated sites, such as infusion centers, trained in Tysabri’s use — and only to patients with relapsing MS who take no other MS medicines.
