Tysabri PML Cases Cause European Regulators to Recommend Stronger Warnings

The European Medicines Agency, an advisory body for drug regulators in Europe, recommended last week that the warning label for the multiple-sclerosis drug Tyasabri be updated following new reports of users developing a rare brain disease known as PML, or progressive multifocal leukoencephalopathy.

Tysabri (natalizumab) is an intravenous injection given every 28 days to treat Crohn’s Disease or multiple sclerosis (MS). It has been shown to prevent relapse, cognitive decline and vision loss which could be associated with multiple sclerosis.

Shortly after Tysabri was introduced in 2004, it was associated with side effects that could lead to PML, which is a potentially fatal brain infection. After three cases of PML resulted in two deaths, a Tysabri recall was issued in 2005, and the drug was re-introduced the next year with stricter guidelines for usage and more prominent warnings about the possible Tysabri PML side effects.

European and American drug regulators have been re-examing the risk of progressive multifocal leukoencephalopathy in recent months, after new reports of PML among Tysabri users surfaced in July 2008. According to filings with the SEC, the drugs makers, Biogen Idec and Elan Corporation, identified two PML cases in Europe, which were the first new diagnosed Tysabria PML cases since 2006.

On September 25, 2008, the European Medicines Agency’s Committee for Medical Products for Human Use (CHMP) called for drug regulators to strengthen the Tysabri progressive multifocal leukoencephalopathy warnings in Europe. They recommended that the drug’s prescription information be updated and strengthened to highlight the potential Tysabri side effects for patients with relapsing-remitting multiple sclerosis (MS).

The European regulatory committee did not call for a Tysabri recall, as they indicated that the benefits of the drug still do outweigh the risks. However, in light of these new PML cases, they felt that the current warnings in Europe need to be strengthened to raise awareness about the risk of the brain disease from Tysabri.

In August 2008, the FDA issued a MedWatch Alert regarding the new reports of PML associate with Tysabri. They indicated that the prescribing information in the United States would be revised to include information for prescribers and patients about the cases of PML that occurred among patients taking Tysabri as a monotherapy. The U.S. drug regulators also recommended that doctors should monitor their patients for signs and symptoms of PML.

that they are investigating the reports to determine what, if any, regulatory actions are necessary regarding the Tysabri side effects.

Progressive multifocal leukoencephalopathy is a rare viral infection which causes inflammation at multiple locations in the brain, leading to progressive brain damage. Symptoms could include loss of vision, impaired speech, paralysis, cognitive decline and weakness. There is no known cure for PML, but the disease can sometimes be slowed or stopped by reducing immunosuppression. In many cases the brain infection is fatal.