FDA Updates PML Risk Info for Natalizumab

As expected, the FDA has approved new label language for the multiple sclerosis drug natalizumab (Tysabri) with additional detail on the risks of progressive multifocal leukoencephalopathy (PML).

The label will now specify that prior immunosuppressant therapy and treatment duration above two years are major risk factors for PML, a life-threatening brain inflammation, the FDA announced Friday.

Post-marketing data collected through January 2011 under the so-called TOUCH registry program established by the drug’s manufacturer, Biogen Idec, indicated that 102 patients have developed PML while under treatment with natalizumab, the FDA said.

A disproportionate number were in their third year of natalizumab treatment and had previously received such drugs as mitoxantrone or azathioprine, which are broad-spectrum immunosuppressants.

The label will include a table showing that the risk of PML is 0.3 per 1,000 patients receiving the drug for less than two years, 1.5 per 1,000 during the third year of treatment, and 0.9 per 1,000 during the fourth year.

However, the new label will not have similar quantitative estimates of the risk associated with previous immunosuppressant therapy.

Physicians are now instructed to ask patients about such treatment before starting patients on natalizumab.

The revision was expected in the wake of data reported recently by Biogen Idec noting that a history of immunosuppressants and treatment duration beyond two years dramatically hikes the risk of PML.

Still absent from the prescribing information, though, is any reference to testing for antibodies to the JC virus, which is the actual cause of PML.

At the recent American Academy of Neurology’s annual meeting, Biogen Idec researchers reported that seronegativity for the virus essentially cancelled out the other risk factors.

But there is no FDA-approved serological assay presently. The FDA is believed to be waiting for results of clinical trials now being conducted by Biogen Idec before making a formal recommendation for such testing.