The manufacturers of the drug, Tysabri, voluntarily withdrew it from the market in February 2005 after two patients in clinical trials died of a rare brain infection called progressive multifocal leukoencephalopathy, or PML. An FDA advisory panel began two days of meeting Tuesday to discuss whether it could recommend the agency allow the drug back on the market.
Should sales resume, more patients — perhaps one in every 1,000 — will fall prey to the often fatal JC virus believed to cause PML, Dr. Russell Katz, director of the FDA's Division of Neurology Products, told the agency's Peripheral and Central Nervous System Drugs advisory committee.
"There will be additional cases of PML and perhaps many cases and there will likely be considerable mortality associated with use of the drug and this is a fact that is not likely to change," Katz told the panel.
Biogen Idec Inc., based in Cambridge, Mass., and Elan Corp. PLC want to resume sales of Tysabri under a risk-management plan that would allow the once-monthly IV drug to be safely used by patients with relapsing MS.
"It is our intention today to assure you that Biogen and Elan, in collaboration with the FDA and prescribing neurologists, can effectively manage the use of this important new drug for the treatment of patients with MS," Dr. Burt Adelman, Biogen Idec's executive vice president, development, told the panel.
The two deaths, from among the 7,000 patients treated with Tysabri during the four months it was on the market, have not deterred MS patients eager for a new and effective drug to treat their disease, for which there is no cure.
Attorney Karen Miller said she stocked up on enough Tysabri to last her into August 2005 and continued taking it after weighing the risks and benefits of doing so each month. Thanks to the drug, she said, she was back to riding her bike, washing windows and running errands.
Miller, 49, knows it's no miracle drug but adds: "It's as close as it comes."
Multiple sclerosis, a disease of the central nervous system, afflicts about 350,000 Americans.
Miller and more than 40 other MS patients and their relatives planned to testify during the two-day meeting. Panel members expected to vote on a recommendation late Wednesday. The FDA is not required to follow the advice of its advisory committees, but usually does.
The risk of PML and other infections remains the primary concern for the regulatory agency.
If Tysabri, also known as natalizumab, returns to the market, the agency recommends its use be restricted and patients be monitored during treatment and for at least five years thereafter to minimize the risk of infection. It would want the risk-management plan proposed by the companies to be mandatory.
FDA officials also remain skeptical about which patients could safely use the drug.
"Primarily because of the risk of PML, which is not well-quantified, it is unclear for which patients the risk-benefit profile would be acceptable," the FDA staff wrote in briefing documents released ahead of the panel meeting.
Three studies recently published by the New England Journal of Medicine found that Tysabri alone or with standard interferon treatment cut the rate of relapse in MS patients by as much as two-thirds after two years and reduced the number of people whose MS got worse, compared to those on a dummy treatment or interferon alone.
"The two-thirds reduction in relapse rate cannot be ignored. It is a striking result," said Dr. Richard Rudick, a neurologist at the Cleveland Clinic who appeared on behalf of Biogen.
Trading of shares in both Biogen Idec and Elan Corp. have been halted for the duration of the two days of FDA meetings, as previously announced.