Tysabri, the monoclonal antibody withdrawn from the market in February last year after progressive multifocal leukoencephalopathy was diagnosed in three patients receiving the drug in clinical trials, will be made available again for patients with relapsing forms of multiple sclerosis, under a restricted distribution program.
The Food and Drug Administration announced in June that the agency had approved Biogen Idec's application for resuming the marketing of natalizumab (Tysabri), with the risk minimization plan, a detailed multistep program called the TOUCH prescribing program by Biogen Idec, the manufacturer of Tysabri.
The FDA now requires prescribing physicians, infusion centers (or physicians' offices that provide infusions) and pharmacies that provide Tysabri to enroll in a risk-minimization program.
The purpose of the detailed, multistep program is “to ensure that physicians and patients are educated about the risks and the benefits of treatment with Tysabri and that only appropriate patients receive treatment,” Dr. Russell Katz, director of the FDA's division of neurology products, said during a teleconference held by the FDA to announce the approval to reintroduce the drug.
The program is also designed to collect information about additional cases of progressive multifocal leukoencephalopathy (PML), and other serious infections “in real time so that we can as rapidly as possible understand both what the true rate of this infection is, but also possibly whether there are any other factors” that may increase a patients risk of PML, he added.
Currently, it is not clear how to predict who will develop PML, how to prevent it, or how to treat it should it occur during treatment with Tysabri, other than to stop treatment as soon as possible, Dr. Katz said. The best estimate currently available is that the risk is about 1 per 1,000 patients treated for up to 2 years, which is based on clinical trial data on use of the drug in patients with multiple sclerosis or Crohn's disease. Little is known about the risk in a larger population or when treatment is continued for longer than 2 years, he noted.
Even with the program in place, other cases of PML are expected, including fatal cases, he said.
“This is balanced against the significant benefits that we believe the drug confers,” Dr. Katz said.
The main elements of the program are that Tysabri can be prescribed, distributed, and infused only by physicians, infusion centers, and pharmacies enrolled in the program, a process that is designed to “minimize the risk of PML, minimize death and disability due to PML, and promote informed risk-benefit decisions” regarding the use of Tysabri, according to the FDA.
A baseline MRI must be obtained in patients before treatment is started to help distinguish multiple sclerosis symptoms that may appear in the future from PML, and physicians are required to evaluate patients 3 and 6 months after the receiving the first infusion, followed by every 6 months; information from these evaluations needs to be sent to the company regularly.
Infusion centers need to inform the company each time a patient has an infusion.
Prescribing physicians are required to be able to diagnose and manage opportunistic infections and PML, or to be prepared to refer patients to an appropriate specialist.
Tysabri was approved in November 2004, and withdrawn by the manufacturer in February 2005; no new cases of PML were reported. The FDA allowed clinical trials to resume earlier this year.
More information on Tysabri, including the new label and a summary of the risk- minimization action plan, is available at www.fda.gov/cder/drug/infopage/natalizumab/default.htm