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The recommendation shows traditional risk-benefit analysis is still working, experts say. But they also believe the Tysabri saga illustrates a trend towards increased use of advisory committees and requirements for drug mechanism data.
The outlook is good that Elan Corp. and Biogen Idec Inc.’s multiple sclerosis drug Tysabri (natalizumab) will return to the market after a unanimous vote last week by FDA’s Peripheral and Central Nervous System Drugs advisory committee. Industry experts are interpreting the probable return an indication that traditional risk–benefit analysis is still viable, but they also see it as a sign of the increasing importance of both the advisory committee system and data on the mechanism of drug action.
Tysabri was taken off the market just about a year ago after it was linked with a small number of deaths from progressive multifocal leukoencephalopathy, a rare brain disease, when taken in conjunction with another MS drug, Avonex (Interferon beta-1a). The FDA is not required to follow the advisory committee’s recommendations, but it usually does. Edward Allera, head of Buchanan Ingersoll PC’s food and drug group, said comments by Robert Temple, the director of the agency's Office of Medical Policy, indicate the drug will definitely come back.
It is still unknown what kind of restrictions the FDA would place on Tysabri, but it is likely that a patient registry will be required and possible that the drug will be indicated only for those who have already been unsuccessful with other products.
The advisory committee’s decision reflects traditional risk–benefit analysis, said James Czaban, an attorney in Heller Ehrman LLP’s FDA group.
“It would be a mistake to read into this a loosening trend,” he said. “Because that’s not the way political winds are blowing.”
According to Jill Alvarez, head of FDA regulatory practice at Nixon Peabody LLP, the advisory committee’s decision shows that for certain drugs -- those that treat serious diseases for which there are few therapeutic alternatives -- decisions about risk should be shared between the agency, the manufacturer, and patients.
“I think it’s part of what’s starting to be a dialog on what drug approval means,” she said. “There’s a recognition that sometimes some risk sharing might be appropriate.”
Alvarez believes risk sharing will become increasingly important as the industry moves towards personalized medicine, and that it may be appropriate for legislators to enact legal protections for drug makers in cases when, due to a lack of alternatives, patients decide to take a drug associated with a high level of risk.
The Tysabri decision re-emphasizes the importance of deciding how risks will be determined as the industry moves towards more sophisticated drugs with narrower indications, Allera said. He noted that it could underscore the necessity of efforts like the Critical Path Initiative. It will also drive demand for including more information about a drug’s mechanism of action in future applications, he said.
Allera noted that the Tysabri saga points out the importance of advisory committees in the approval process. The drug was initially approved without including the advisory committee step.
“If that had been followed, it might have diffused some of the concerns,” he said. “In the future, first-in-class drugs will go through an advisory committee.”
Czaban agreed that for first-in-class drugs, or drugs for diseases with no satisfactory alternative therapies, it “is probably best” to have an advisory committee evaluation.