Setting strict guidelines, the US Food and Drug Administration (FDA) has allowed the return of the multiple sclerosis (MS) drug natalizumab (Tysabri).
Tysabri had received FDA approval in November 2004, only to be pulled from the market three months later after several patients in clinical trials developed a rare but deadly viral infection of the brain called progressive multifocal leukoencephalopathy (PML).
The FDA put the clinical trials on hold in February 2005, but allowed them to resume one year later, in February 2006, with no additional cases of PML reported.
"This is one of the very rare cases in which a drug withdrawn from the market for safety reasons has been returned back to the market after appropriate steps have been taken," says Dr. Steven K. Galson, director of the FDAs Center for Drug Evaluation and Research.
"In this case, we made the assessment that the benefits of this drug outweigh the risks," Galson adds. "We are certain that patients are willing to take this risk because of the potential benefits of the drug."
Studies have found that treatment using Tysabri reduced the rate of relapse in MS patients by as much as two-thirds after two years, and reduced the number of patients whose symptoms worsened.
"We are very pleased with the review and the outcome from the FDA," says Dr. Patricia O' Looney, director of biomedical research at the National Multiple Sclerosis Society. "It's good news for people with MS. It's good news because it provides an option for treatment.
"The important thing is to have the drug back on the market, so that patients and doctors can discuss whether or not to use the drug for a particular patient," O' Looney says.
Still there are risks. "Currently, the best estimate we have of the rate of occurrence of PML is about one in 1",000 patients treated," says Dr. Russell Katz, of the FDAs Division of Neurology Products. "We know little about what the risk would be in a larger population or what the risk would be if treatment continues beyond two years," he says.
With the drug's return to the market, there will undoubtedly be other cases of PML and additional deaths, Katz adds. But, he says, "This is balanced against the significant benefit that the drug confers."
The New Guidelines
Tysabri will only be available through a risk management plan, called the TOUCH Prescribing Program. To receive Tysabri, patients must confer with their doctor, understand the risks and benefits of the drug and agree to all of the guidelines of the program. Some of those guidelines include...
Only those registered with the program and who agree to comply with it will be able to prescribe the drug.
Only infusion centers registered and authorized will be able to administer Tysabri intravenously.
Only pharmacies registered with the program will be able to dispense Tysabri to authorized infusion centers.
Only patients enrolled in the program and who agree to comply with it will be able to receive the drug.
All program prescribers, pharmacies, infusion centers and patients will be educated about the program as well as the risks of Tysabri.
O' Looney says the FDA restrictions are warranted. "'We don't know enough about the drug. The results from the two-year study were remarkable in terms of its impact on disease activity and progression, but there is a concern about PML. So all of these restrictions are justified," she says. "It's all for the protection of the patient."
In addition, safety surveillance-including regular magnetic resonance imaging (MRI), monitoring and reporting of PML and other serious infections and deaths, and systematic tracking of patients and drug disposition-will be carried out, according to the FDA.