WASHINGTON – Dozens of multiple sclerosis patients asked federal health advisers Tuesday to let them decide whether to take Tysabri, a promising drug that was pulled from the market after it was linked to a rare, often-fatal brain infection.
“I am at the end of my road, in terms of what I can take. I want it to be my choice,” said Barbara Crooks, 48, who traveled with her husband, David, from the Pittsburgh area to testify before a Food and Drug Administration advisory committee.
In statements frequently punctuated by sobbing pleas, patients said the risk of MS was greater than that of Tysabri.
“This disease and its symptoms are progressive and it will not wait for anyone’s approval,” said Pamela Sue Clark, a Salt Lake City mother of two who urged the panel to allow the drug to be sold again.
The committee began two days of discussions of whether it could make that recommendation despite evidence the drug would kill some of the patients it was meant to treat. A vote on a recommendation to the FDA was expected late Wednesday. Although the FDA is not bound by the recommendations of its advisory panels, it usually follows them.
The manufacturers of Tysabri (pronounced ty-SAH-bree) withdrew it from the market in February 2005 after two patients in clinical trials involving 7,000 people died of a rare brain infection called progressive multifocal leukoencephalopathy, or PML. The drug had been sold for just four months.
Anita Smith was one of the two to die. On Tuesday, Smith’s daughter, Beth Ann Smith, read a letter from her father, Walter, lamenting his wife’s death.
“We were never told Tysabri would result in Anita’s death. If we had known that, we would have happily stayed away from the trial,” the letter read.
Should sales resume, even more patients — perhaps one in every 1,000 — will get 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.
Multiple sclerosis, a disease of the central nervous system, afflicts about 350,000 Americans. There is no known cure.
Biogen Idec Inc. and Elan Corp. PLC want to resume sales of Tysabri under a still-evolving, risk-management plan that would allow the once-monthly IV drug to be 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 companies have recommended that if neurological symptoms suggestive of PML appear, treatment with Tysabri should cease.
But there is doubt that doctors would be able to discriminate MS symptoms from the early onset of PML, said Dr. Susan McDermott, a neurologist and FDA clinical reviewer. That difficulty “caught the eye” of FDA reviewers, she said.
And patients may be reluctant to report symptoms if it meant they’d lose access to the drug, said panel member Dr. Justin McArthur, a neuroscience specialist at the Johns Hopkins Medical Institutions.
Charlie Richardson, who was diagnosed with MS in 1988, told the panel that he was willing to risk the infection.
“There is a one-in-1,000 chance of developing MS. After winning that lottery, I am fully willing to become one of the 999 who don’t develop PML while taking Tysabri,” a tearful Richardson told the panel.
If Tysabri, also known as natalizumab, returns to the market, FDA staff recommended that patients be monitored during treatment and for at least five years thereafter to minimize the risk of infection.
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.