The label of the immunomodulator efalizumab will soon have a black box warning describing the potential risks of progressive multifocal leukoencephalopathy and other life-threatening infections, because of postmarketing reports of these serious infections, the Food and Drug Administration announced last month
Some cases have required hospitalization and some have been fatal, according to a statement issued by the FDA. In addition to progressive multifocal leukoencephalopathy (PML), the boxed warning will list bacterial sepsis, viral meningitis, invasive fungal disease, and other opportunistic infections as risks associated with efalizumab (Raptiva).
The FDA has also requested that Genentech, the manufacturer of efalizumab, submit plans for a risk evaluation and mitigation strategy. Under legislation passed in 2007, the agency can require manufacturers to make safety labeling changes, and to plan a strategy for evaluating and managing a drug's risks, to ensure that the benefits of a drug outweigh its risks, when a safety issue is identified.
“Doctors and other prescribers should carefully evaluate and weigh the risk/benefit profile of Raptiva for patients who would be more susceptible to these risks,” Dr. Janet Woodcock, the director of the FDA's Center for Drug Evaluation and Research, said in the statement.
In a letter sent to health care professionals, Genentech described a case of PML in a patient treated with efalizumab for psoriasis, the first confirmed case associated with the immunosuppressive human monoclonal antibody.
The patient is a 70-year-old man, who had been treated with efalizumab for chronic plaque psoriasis for more than 4 years. He is currently hospitalized, a spokesperson for Genentech said.
PML is a rare, often fatal progressive disorder that affects the central nervous system. It is caused by activation of the JC virus, which is latent in more than 80% of healthy adults and usually causes disease only in immunocompromised patients.
“Physicians should consider PML in any patient treated with Raptiva who presents with new onset neurologic manifestations” and should also consider a brain MRI, lumbar puncture, and consultation with a neurologist, the letter advises. Efalizumab should be stopped in any patient who develops PML, and antiviral therapy and other appropriate treatments should be considered, the letter adds.