August 26, 2008 — Two new cases of progressive multifocal leukoencephalopathy (PML) have been reported in European multiple sclerosis patients receiving natalizumab (Tysabri, Biogen Idec, Inc), the US Food and Drug Administration (FDA) warned yesterday.

Both patients had been receiving natalizumab monotherapy for longer than 1 year, according to an alert issued by MedWatch, the FDA's safety information and adverse event reporting program. In contrast, prior reports of PML had involved use of natalizumab with other immunomodulatory agents.

"While the two patients who developed PML were on monotherapy, the FDA still believes that Tysabri monotherapy may confer a lower risk of PML than when Tysabri is used together with other immunomodulatory medications," the agency emphasized in a news release.

The monoclonal antibody was first approved by the FDA in November 2004 for the treatment of multiple sclerosis and was later withdrawn by the manufacturer in February 2005 after 3 patients developed PML during clinical trials.

After reviewing the study data to confirm the absence of additional PML cases, the reintroduction of natalizumab into the US market was accompanied by a restricted distribution and risk-management program, known as TOUCH. The drug was later approved in January 2008 for the treatment of Crohn's disease.

Under the TOUCH program, each natalizumab-treated patient is closely monitored for the development of PML and other opportunistic infections. According to the FDA, no new PML cases have been reported either among 7500 US patients taking the product for more than 1 year or among an additional 3300 patients who have received treatment for at least 1.5 years.
"Healthcare professionals should continue to monitor patients for sign and symptoms of PML," the agency advised. "Additionally, Tysabri should not be infused if PML is suspected."

Natalizumab monotherapy is indicated to delay the accumulation of physical disability and reduce the frequency of clinical exacerbations in patients with relapsing forms of multiple sclerosis; it also may be used to induce and maintain clinical response and remission in adult patients with moderately to severely active Crohn's disease who have evidence of inflammation. Use of natalizumab is generally reserved for patients who have had inadequate response to, or are unable to tolerate, conventional therapies.

Adverse events related to use of natalizumab should be reported to the FDA's MedWatch reporting program by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, MD 20852-9787.


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