FDA Informs Doctors about Reports of Progressive Multifocal Leukoencephalopathy (PML)

The FDA has issued a notice to healthcare providers with information about two new reports of progressive multifocal leukoencephalopathy (PML), a rare brain disease, which have occurred among two patients in Europe who were receiving the multiple sclerosis drug Tysabri.

Information about the two cases of this progressive and potentially fatal disease were first disclosed earlier this month in filings made by the drug manufacturers, Biogen Idec and Elan, with the Securities and Exchange Commission. Both users developed PML after taking Tysabri for at least 14 months, without simultaneous use of another multiple sclerosis drug.

These new cases are important, since they are the first reports of the rare brain disease among Tysabri users since the drug was reintroduced two years ago. It was removed from the market in 2005 after two deaths from three cases of PML were associated with the drug. It was allowed to return in 2006 with stricter guidelines and more prominent warnings about progressive multifocal leukoencephalopathy as a potential side effect of the treatment.

The FDA posted the information Monday through their MedWatch Alert System, urging doctors to only prescribe Tysabri to patients who are enrolled in a special program, known as the TOUCH Prescribing Program.

TOUCH is a risk minimization plan, where every patient is closely watched and monitored for PML and other adverse opportunistic infections. The program is also designed to assess the risk of PML, promote informed decisions among users and to minimize the number of disabilities and deaths due to progressive multifocal leukoencephalopathy.

Tysabri was initially launched in 2004, as an intravenous injection given every 28 days to treat multiple sclerosis (MS). Earlier this year, the FDA approved an additional use for Tysabri to treat Chron’s disease, where patients have failed other treatments, such as Remicade and Humira.

PML, also known as progressive multifocal leukoencephalitis, is characterized by progressive damage and inflammation at multiple locations in the brain, leading to permanent brain damage. Symptoms of PML include paralysis, weakness, impaired speech, and loss of vision. It is rare viral disease, which has no effective cure and can be fatal.

The two new cases of PML in Europe were reported among patients with multiple sclerosis who received Tysabri as a monotherapy, and both used the drug for more than a year.

Previous cases of PML associated with Tysabri had occurred only in multiple sclerosis patients who took other immunomodulatory drugs in combination with the medication. The FDA indicates that data suggests individuals who use Tysabri alone have a lower risk of developing PML than those who use it with other immunomodulatory medications.

No new cases of PML associated with Tysabri have been reported in the United States. At least 7,500 people have used the drug for more than a year in the U.S. and about 3,300 patients received the drug for at least one and a half years. Approximately 39,000 patients worldwide have been treated with Tysabri, with 12,000 of them having undergone treatment for at least a year.

The FDA and the manufacturer are reviewing changes to the product label to inform patients and prescribers that the use of Tysabri as a monotherapy has resulted in cases of progressive multifocal leukoencephalopathy.