Tysabri Labeling Changes Sought by European RegulatorsSep 25, 2008 | Parker Waichman LLP
The European Medicines Agency wants to raise awareness of a deadly brain infection associated with the drug Tysabri. It recommended Thursday that the product information for Tysabri (natalizumab) be updated to include more information about the risk of progressive multifocal leukoencephalopathy (PML).
PML attacks the brain and central nervous system and is usually fatal. It is caused by a polyomavirus, called the JC virus. The JC virus is often acquired during childhood. Most adults have been infected with the JC virus but do not develop PML. The virus appears to remain inactive until something (such as a weakened immune system) allows it to be reactivated and start to multiply. People with a weakened immune system or people taking drugs that suppress their immune system (immunosuppressants) are most likely to get the disease. Symptoms include vision problems, loss of coordination, and memory loss. Patients who survive the disease are often permanently disabled.
In the U.S. Tysabri was taken off the market in 2005 after three patients in clinical trials developed PML. But the drug was reapproved in 2006, although it was subject to restrictions. Tysabri is now available only to patients with relapsing multiple sclerosis (MS) or Crohn’s disease (CD) who are enrolled in the risk minimization plan called the TOUCH Prescribing Program. Under the TOUCH Prescribing Program, every Tysabri-treated patient is closely monitored and followed for the occurrence of PML and other serious opportunistic infections.
Just last month, Elan and Biogen Idec announced that Tysabri had been associated with two more cases of PML, this time among patients taking it in Europe. The most disturbing aspect of the latest PML cases, however, was that both patients had been taking Tysabri as monotherapy - with no other drugs. It had been theorized that patients contracting PML had done so because of exposure to multiple medications and that monotherapy with Tysabri was less risky.
Those cases have prompted reviews of the medicine in the Europe, as well as the U.S. Following a review of the available data, the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) concluded that the benefits of Tysabri continue to outweigh its risks in the treatment of relapsing-remitting MS, but that the existing warning on the risk of PML should be strengthened to heighten patients' and prescribers' awareness about this side effect.
In addition, the Committee requested an update to the 'Physician Information and Management Guidelines for Multiple Sclerosis Patients on Tysabri'. These guidelines are part of the agreed risk management plan for Tysabri, which set out a series of risk minimization measures. Following the update, doctors will be able to obtain more detailed guidance on how to differentiate PML from a relapse of MS, and how to manage suspected cases of PML.
The CHMP's recommendation will now be sent to the European Commission for the adoption of a decision.
Last month, The U.S. Food & Drug Administration (FDA) said it was working with Elan and Biogen Idec, the manufacturers of Tysabri, to amend the product labeling to inform prescribers and patients that cases of PML have occurred in patients taking Tysabri as monotherapy.