Additional PML Brain Infection Cases Linked to Tysabri and Rituxan

New cases of a rare brain infection, progressive multifocal leukoencephalopathy (PML), have been liked to the lymphoma and arthritis drug Rituxan and the multiple sclerosis (MS) drug Tysabri. The cases have regulators in the U.S. and Europe searching for ways to reduce the risks of patients developing the often fatal brain infection.

Progressive multifocal leukoencephalopathy is a viral infection that causes inflammation at multiple locations in the brain, leading to potentially life-threatening 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.

On Friday, the FDA and Genentech issued a warning about a new Rituxan brain infection case reported in a 73-year-old woman who was taking the drug for treamtent of rheumatoid arthritis. She is the third arthritis patient to contract PML on Rituxan, but the first patient to contract the brain infection who was not also receiving anti-tumor necrosis factor therapy, known as TNF-blockers.

Neither the FDA alert or a “Dear Healthcare Professional” letter issued by Genentech indicated whether the patient was still alive. The other two patients who were diagnosed with Rituxan PML died from the condition.

Rituxan (rituximab) is a chimeric monoclonal antibody drug that helps the immune system fight specific types of cells, like lymphoma cancer cells. The drug, which is manufactured jointly by Genentech, Inc. and Biogen Idec, Inc., was approved by the FDA in 1997 for treatment of non-Hodgkin’s lymphoma and rheumatoid arthritis, generating annual sales of about $2.3 billion. The drug makers are currently petitioning the FDA to expand the approved uses for Rituxan to include treatment of chronic lymphocytic leukemia together with chemotherapy.

The FDA is reviewing Rituxan’s connection to the deadly brain virus, and whether the long-term use of Rituxan, without interrupting the treatment, may be a potential factor increasing the risk of PML. Some experts have suggested that having patients take time away from the drug’s use, referred to as “drug holidays” may give their body the opportunity to fight off the virus that causes the infection and reduce the risk of progressive multifocal leukoencephalopathy from Rituxan. There is already a black box warning on the label about the possible link between Rituxan and PML.

The brain infection has also been linked to the multiple sclerosis and Chrohn’s disease drug, Tysabri. In 2004, a link between PML and Tysabri led to a temporary recall of the medication, which was reintroduced in 2006 under more stringent usage guidelines to reduce the risk of users developing the brain infection.

In Europe, regulators disclosed last week that the number of PML brain infections from Tysabri was significantly higher than previously thought.

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) indicated 23 PML brain infection cases have been linked to Tysabri since the drug was reintroduced in 2006. The previously reported number of cases was only 13. According to the Wall Street Journal, the FDA has confirmed the new number and indicates that they are continuing the review the risk.

Tysabri (natalizumab) is an intravenous injection given every 28 days to treat MS and Crohn’s Disease. Manufactured by Biogen Idec Inc. and marketed with Elan Corp PLC, Tysabri has been shown to prevent relapse, cognitive decline and vision loss associated with MS. Sales of Tysabri bring in about $1 billion annually.

In April 2009, reports of PML brain infections resulted in a recall of Raptiva, a once-weekly injection that was prescribed to treat psoriasis. Following four brain infection reports, the FDA and Genentech, which also manufactured Raptiva, determined that the potentially life-threatening risk of progressive multifocal leukoencephalopathy outweighed the benefits provided by that medication.