The Food and Drug Administration is weighing whether patients’ course of treatment for the widely used cancer drug Rituxan should be changed. Rituxan may pose less of a risk of developing progressive multifocal leukoencephalitis (PML) if it is used for a shorter period or with breaks, according the FDA and the Wall Street Journal.

The drug is co-marketed by biotechnology companies Genentech Inc. of California and Biogen Idec Inc. of Massachusetts. Rituxan, which is used to treat lymphoma, a cancer of immune-system cells, had $2.6 billion in U.S. sales in 2008.

PML is a viral infection that affects the white matter of the brain. PML is caused by reactivated JC virus. Latent JC virus is present in about 80 percent of adults. Patients with PML exhibit neurological symptoms like confusion, dizziness or loss of balance, difficulty talking or walking, and vision problems. PML gets worse over time, and is usually fatal. There is no treatment or cure for the disease. It is often associated with drugs that suppress the immune system.

A study released in March in the medical journal, Blood linked Rituxan to 57 cases of PML between 1997 and 2008. Of 57, 51 died. The median time between their diagnosis and death was about two months.

The study’s researcher commented: "The potential contribution of Rituxan to the development of PML is unknown; however, it cannot be excluded."

While Rituxan has been linked to a higher number of PML cases, some are not calling for a recall of Rituxan because it is frequently the best option for patients with life-threatening cancer. It is questionable whether the drug should be used in patients who do not have life-threatening diseases. There are typically more options for patients with rheumatoid arthritis, another ailment which Rituxan is approved to treat.

Doctors say Rituxan is also used "off label" for conditions not approved by the FDA, including lupus and psoriasis. FDA officials said they are aware of some off-label uses, which are legal so long as the drug maker does not promote them. Genentech said it doesn't promote off-label use of Rituxan.

Doctors at the FDA have been looking at the long-term uninterrupted use of Rituxan as a potential factor in PML. By suppressing the immune system, the drug may give free rein to the virus, normally under check, that causes the brain disease.

"We've had discussions at the FDA about whether drug holidays or limitations on the duration of therapy might reduce the risk of PML and other serious adverse effects of chronic immunosuppression," said John Jenkins, director of the FDA's drug approval section.

Drug holidays themselves can cause problems, though. "Sometimes [after a break from the drug], the disease recurs more severely and requires higher doses to bring the disease back under control," Dr. Jenkins said.

The FDA warned of the possible link between Rituxan and PML in 2006. Currently, Rituxan's label has a "black box" warning about PML, the strongest possible warning.



Reports of adverse events associated with Rituxan, including PML, should be reported to the FDA.



The FDA can be contacted via:
Online at www.fda.gov/medwatch/report.htm
Phone at 1-800-FDA-1088
Fax at 1-800-FDA-0178, using the MedWatch Form 3500
(available at www.fda.gov/medwatch/ getforms.htm)
Mail, using the postage-paid MedWatch Form 3500 (see above), to MedWatch, 5600
Fishers Lane, Rockville, MD 20852-9787



For more information please see:

http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm109106.htm

http://online.wsj.com/article/SB124381351149970563.html

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