FDA Approved Controversial MS Drug Too Quickly: Expert

But others say Tysabri, now withdrawn from market, met standard data requirements

FRIDAY, Feb. 17, 2006 (HealthDay News) -- A multiple sclerosis drug pulled from the market early last year due to safety concerns was initially approved too quickly and probably should not go back on the market, at least not without more data, according to an expert writing in this week's British Medical Journal.

The article arrives a day after the U.S. Food and Drug Administration announced that the makers of Tysabri -- Biogen Idec Inc. and Elan Corp. PLC -- could resume clinical trials for MS patients who were previously treated with the drug under an investigational study.

An FDA advisory committee will also convene March 7 and 8 to consider the re-admission of the drug to market.

But the author of the BMJ article believes Tysabri -- whose generic name is natalizumab -- was approved too quickly in the first place.

"The rate at which Tysabri was first tracked is absolutely unacceptable for a condition like multiple sclerosis, which can last for 30 years," said the author, Dr. Abhijit Chaudhuri, a consultant neurologist for the Essex Centre for Neurological Sciences at Oldchurch Hospital, Romford, Essex, in England. "They did not even look into the side effects and this is unbelievable. It's a major failing."

Tysabri was pulled from the market on Feb. 28, 2005, after reports that three patients taking it had developed progressive multifocal leucoencephalopathy (PML), a progressive, neurodegenerative disease. The suspension took place just three months after the FDA granted accelerated approval of the drug for the treatment of relapsing forms of MS.

According to the National Institute of Neurological Disorders and Stroke, multiple sclerosis is an unpredictable disease of the central nervous system that can range from relatively benign to somewhat disabling to devastating. Most MS patients experience their first symptoms between the ages of 20 and 40, and most suffer muscle weakness in their extremities and difficulty with coordination and balance. These symptoms may be bad enough to hamper walking or even standing; in worst cases, MS can produce partial or complete paralysis.

Tysabri is a monoclonal antibody, engineered to attach itself to white blood cells called lymphocytes and prevent them from entering the brain, where they do damage that causes the disabling symptoms of MS. Tysabri had also been used to treat Crohn's disease.

Resumption of clinical trials using the drug doesn't pose a problem for Chaudhuri. "It's very simple," he said. "If a study is being conducted with ethical approval and physicians and participants are well aware of the risks, I have nothing to disagree about. Any scientific study where use of new product is closely monitored should go ahead."

But he is critical of the initial approval process for the drug. According to Chaudhuri, the FDA approved Tysabri only on the basis of short-term results from two unpublished trials, and before final data were available.

"Based on what we've seen so far, there is no evidence to suggest that this is very effective for MS," he said. "We're talking about a condition that affects young people fairly early in life and which lasts for 30 to 40 years, so it's a lifelong disease. Before you start using that, you must have convincing and compelling evidence that long-term disability is significantly reduced, at no cost for side effects. And I don't think we have that kind of information."

Chaudhuri's views aren't necessarily shared by other experts or by the companies involved, however.

"Tysabri has shown outstanding benefit in people with MS," said Davia Temin, a spokeswoman for Elan. "At the time of the suspension, Elan and Biogen put safety first and launched a rigorous medical scientific review of more than 3,000 patients treated with Tysabri. The results of this yielded no new confirmed cases of PML beyond the three previously reported."

Dr. William Sheremata, professor of neurology and director of the MS Center at the University of Miami School of Medicine, said, "MS is a disabling disorder and there really is a need to look for better treatments. The FDA's action was an attempt to try to keep the cost of drug development down, which has become a terrible problem. The agency was relying on over 30 years of experience with monoclonal antibodies."

But the resumption of the trial is still a far cry from restoring the drug to pharmacy shelves, and the outcome of next month's FDA advisory committee meeting remains unclear.

In a statement released Thursday, the FDA said that, "Although this treatment has been shown to have benefit in patients with relapsing-remitting MS, concern about the risk of PML associated with use of Tysabri remains."

The agency said it has worked with Biogen-IDEC over the past year to make sure that no other clinical trial participants have shown early evidence of PML, and to determine ways of minimizing the risk.

According to officials at Cambridge, Mass.-based Biogen IDEC, any return of Tysabri to the market would involve new labeling warning of potential risks to patients with weakened immune systems, who are most at risk for PML.

More information

Find out more about Tysabri at the U.S. Food and Drug Administration.

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