June 5, 2006 -- The FDA is letting the Tysabri back on the market under a restricted distribution program.drug
The FDA first approved Tysabri in November 2004. Tysabri’s maker, Biogen-Idec, took Tysabri off the market in February 2005 after three people out of about 3,000 patients taking Tysabri in clinical trials developed a rare, serious brain infection called progressive multifocal leukoencephalopathy (PML). Two of those patients died.
The FDA is rolling out a risk-minimization plan along with Tysabri's return to the market. The plan is designed to inform patients, doctors, pharmacists, and infusion centers about Tysabri’s risks and to quickly flag PML cases in patients taking Tysabri.
However, FDA officials aren’t ruling out the possibility of more cases of PML in patients taking the drug.
Rare Return to Market
“This is one of the very rare cases in which a drug withdrawn from the market for safety reasons has been returned back to the market after appropriate steps have been taken,” the FDA’s Steven Galson, MD, MPH, told reporters in a conference call.
Galson directs the FDA’s Center for Drug Evaluation and Research. He says the FDA has worked “closely” with Biogen-Idec on the new plan.
In Tysabri’s clinical trials, about one in 1,000 participants developed PML after taking Tysabri for up to two years. It’s not clear if that rate will hold in the general public or for longer use, the FDA’s Russell Katz, MD, told reporters in the teleconference. Katz works in the neurology products division of the FDA’s Center for Drug Evaluation and Research.
PML is still a risk with Tysabri, note both Galson and Katz.
"Without prohibiting use of the drug, you can never be sure that this won’t happen again. But we think that the steps that we’ve taken are prudent to reduce that risk,” Galson says.
More Cases Possible
“There’s much we don’t know about this,” Katz says. “We expect, yes, that there will be other cases and there probably will be additional deaths. This is balanced against the significant benefit that we believe the drug confers,” Katz says.
Speaking about PML, Katz says, “We don’t know how to predict who’s going to get it, we don’t know how to prevent it, and we don’t know how to treat it if it occurs.”
Galson notes that until Tysabri’s new risk-minimization program has been in effect for some time and physicians have seen patients go through rounds of therapy, “there may be additional things that we will learn.”
“The size of the clinical trials that have taken place and the duration is not adequate for us to know for certain that there isn’t something else that’s going to happen or further information that will be gained about this condition,” Galson says.
“We made the assessment that the benefits of this drug outweigh the risk for this particular condition,” Galson says. “Multiple sclerosis ... is a debilitating condition and we are certain that patients are willing to take this risk because of the potential benefits of the drug. So that’s why we’re doing it.”
Tysabri is a monoclonal antibody given usually once a month by health care professionals. It’s used to treat patients with relapsing forms of MS in order to reduce the frequency of flare-ups.
The new rules mean that before taking Tysabri, patients must enroll in a risk-minimization program designed by Biogen-Idec. Patients also need to get a brain scan using magnetic resonance imaging (MRI) before taking Tysabri.
Doctors who prescribe Tysabri, pharmacies that dispense the drug, and infusion sites that administer the drug must also enroll in the risk-minimization program.
Tysabri shouldn’t be used in combination with other immune-system modifying drugs. It’s intended for patients who have not responded adequately to -- or cannot tolerate -- other treatments for MS, states the FDA. However, other uses of Tysabri aren’t forbidden on the label.
In February 2005, after Biogen-Idec took Tysabri off the market, the FDA put Tysabri’s clinical trials on hold.
A year later, the FDA let a Tysabri clinical trial resume after a re-examination of patients in Tysabri’s previous clinical trials confirmed no additional cases of PML.
In March 2006, the FDA consulted its Peripheral and Central Nervous Systems Drugs Advisory Committee about ways to cut the risk of PML while making Tysabri available to appropriate patients.
The committee recommended a risk-minimization program with mandatory patient registration and periodic follow-up for Tysabri. The newly approved plan is the result. It’s designed to identify any PML cases as quickly as possible and to learn more about which patients may be at higher risk.
The plan’s rules include:
- Tysabri will only be prescribed, distributed, and infused by prescribers, infusion centers, and pharmacies registered with the program.
- Tysabri will only be administered to patients who are enrolled in the program.
- Before starting Tysabri, patients must get magnetic resonance imaging (MRI) to help differentiate future MS symptoms from PML.
- Patients on Tysabri are to be evaluated at 3 and 6 months after the first infusion and every 6 months after that, and their status will be reported regularly to Biogen Idec.
Additional information on the TOUCH Prescribing Program is available from the companies by calling 1-800-456-2255.