WEDNESDAY, March 1, 2006 (HealthDay News) -- New data on a controversial multiple sclerosis drug pulled from the market a year ago found that the drug actually appears to be effective and safe, at least for the short term.
However, the researchers can't yet say the medication is risk-free.
Three patients taking the drug, Tysabri (generic name natalizumab) had developed progressive multifocal leucoencephalopathy (PML), a progressive, neurodegenerative disease. Two of those patients died, one with multiple sclerosis (MS) and one with Crohn's disease. In the aftermath of these events, questions were also raised about the drug's effectiveness.
A U.S. Food and Drug Administration advisory committee will no doubt take this updated picture into account when it considers allowing Tysabri back on the market at a meeting March 7 and 8.
"The efficacy data was very encouraging and the extra year of follow-up during which people who had taken Tysabri were evaluated did not reveal any additional cases of PML, which is also very encouraging," said Dr. John Richert, vice president for research and clinical programs at the National Multiple Sclerosis Society. "The issue now is for the FDA to evaluate all of the efficacy data and all of the risk data and come up with the wisest decision possible."
The makers of Tysabri -- Biogen Idec Inc. and Elan Corp. PLC -- were also pleased with the findings.
"The two-year data from two Phase III clinical trials of Tysabri, among the largest ever in MS, alongside findings from a comprehensive safety evaluation, underscore the compelling efficacy of Tysabri in MS and the extensive nature of the safety evaluation -- both will be used to further define the benefit-risk profile," said Davia Temin, spokeswoman for Elan. "The two-year data along with the safety evaluation are part of regulatory filings currently under review with the FDA and EMEA. The FDA has granted Priority Review to the Tysabri sBLA [biologic license application] and we anticipate action in late March."
Tysabri was pulled from the market on Feb. 28, 2005, after reports that three patients taking it had developed PML. The suspension took place just three months after the FDA had granted accelerated approval of the drug for the treatment of relapsing forms of MS.
In February of this year, the U.S. Food and Drug Administration announced that Biogen and Elan could resume clinical trials for MS patients who were previously treated with the drug under an investigational study.
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.
The new findings appear in three papers in the March 2 issue of the New England Journal of Medicine.
The first trial, involving 942 patients, found that Tysabri reduced the risk of progression of disability by 42 percent over two years and the rate of clinical relapse at one year by 68 percent. The drug also reduced the accumulation of brain lesions, which are hallmarks of the disease.
The second trial found that, when combined with interferon beta-1a, Tysabri reduced the risk of relapse by 55 percent. The combination therapy also reduced the risk of progression of disability by 24 percent over two years. This study involved 1,171 patients.
Finally, and perhaps most encouraging, the third study found no additional cases of PML among 3,116 patients who had taken Tysabri.
"We concluded that at this particular time there is no evidence that there are more PML cases," said Eugene Major, co-author of the third paper and chief of the laboratory of molecular medicine and neuroscience at the U.S. National Institute of Neurological Disorders and Stroke.
The risk is still high, however, Major said. "One in 1,000 is substantial. Questions remain about risk," he said.
"There probably is some definite risk of PML in people who are on Tysabri," added Richert, of the National Multiple Sclerosis Society. "What's not clear yet is whether or not people on Tysabri also have to be otherwise immunosuppressed or immuno-modulated with other medications in order to have that risk."
The National Multiple Sclerosis Society conducted a survey of about 800 people with MS to gauge their views on Tysabri and has given this data to the FDA to consider at the upcoming advisory committee meeting. Many people said they wanted more information on Tysabri before making a decision on whether they would be willing to take it.
The society feels much the same way, Richert said. "Rather than proselytize for or against approval, our emphasis has been make sure that the FDA conducts as thorough an evaluation as humanly possible and comes to the wisest decision possible," he said. "We did give them names of people to testify but they have not told us who, if anyone, from our list they have chosen."
More information
For more on MS, visit the National Multiple Sclerosis Society.
