FDA gave Tysabri accelerated approval
Third Person Dies and Tysabri may be the Cause
A third patient has died after contracting a rare brain disease while being treated with Tysabri, the multiple sclerosis drug that Biogen Idec Inc. and Elan Corp. PLC pulled off the market a month ago.
The
companies said late Wednesday that a patient who was enrolled in a 2003 Phase
III clinical trial testing Tysabri for the treatment of Crohn's disease is
now believed to have died from progressive multifocal leukoencephalopathy,
or PML, an extremely rare brain infection.
The patient, who died in 2003, was originally classified as succumbing to a form of brain cancer, and had taken eight doses of Tysabri over the course of 18 months.
The clinical trial was conducted by Elan. A reexamination of the patient's files led researchers to retest the deceased's brain tissue, according to Biogen.
The most recently suspected case of PML is the first linked to
the use of Tysabri alone. The two previously confirmed cases of PML involved
patients who were enrolled in a clinical trial testing Tysabri with Avonex,
an older Biogen drug for multiple sclerosis.
Up to now, many industry observers had suspected that the PML cases were triggered by some negative interaction between Tysabri and Avonex, rather than just by Tysabri alone. That belief had kindled hope among investors and MS patients that Tysabri would eventually be found safe enough to return to the market.
Wednesday's news fanned fears that the root of the problem may lie with Tysabri itself, rather than with a combination of the two drugs.
Tysabri, once hailed as a breakthrough in MS treatment, is part
of a new class of drugs that uses antibodies to manipulate the immune system.
PML is most often seen in patients with highly compromised immune systems,
such as those suffering from AIDS.
Tysabri
had shown better results in MS patients than other drugs on the market, and
had also been tried in people with Crohn's disease and rheumatoid arthritis.
It works by suppressing the immune system in the brain, which is over-active
in MS. PML is often seen in patients with Aids, where the immune system is
suppressed.
The FDA gave Tysabri accelerated approval for the treatment of MS in November 2004 based on strong early Phase III clinical data. Biogen and Elan since have suspended all clinical trials for the drug, pending an investigation into the cause of the PML cases.
 Figure
1Brain in progressive multifocal leucoencephalopathy |
Though PML is rare, the virus that causes it is believed to lie dormant in more than half the population. The virus only becomes active when the immune system
is unable to protect the central nervous system.
A Biogen Idec spokesman, Tim Hunt declined to say how many cases have been reviewed of the 3,000 patients that participated in trials of Tysabri. ''We are looking up and down and reviewing all the clinical trial data," he said. After the review, Hunt said, the companies would meet with regulators to discuss restarting clinical trials involving Tysabri. Trials were discontinued when the companies voluntarily stopped distributing the drug to doctors Feb. 28.