The California-based biotech firm Genentech has announced the gradual withdrawal of its psorasis drug Raptiva from the market by June 8, 2009.

Behind the decision

The decision was made after three Raptiva patients, two of whom died, were diagnosed with progressive multfocal leukoencephalopathy, PML, a rare, irreversible, and usually fatal brain disease. A fourth patient with similar symptoms died of unknown causes.

Though Genentech and the Food and Drug Administration, which appoved the drug for the treatment of psoriasis in 2003, had recently strengthened the warning label to highlight the risk of opportunistic infections, including PML, the company determined that the risk of PML outweighed Raptiva’s benefits in controlling psoriasis.

No way has been found to predict which patients were likely to develop PML, nor to find a way to minimize that risk.

Raptiva is administered by weekly injections. The patients who developed PML had been taking the drug for at least three years. Raptiva works by suppressing the abnormal immune system response that triggers psoriasis, which causes painful and scaly skin rash and joint pain.

But immune suppression also makes the body more susceptible to opportunistic infection. The new Raptiva “Black Box” label warning highlighted the risks of bacterial sepsis, viral meningitis, and invasive fungal infection, as well as PML.

Other drugs linked to PML risk

Several other immune suppressing drugs have been linked to increased risk of PML, including:

--Tysabri, co-marketed by Biogen and Elan, was approved for the treatment of multiple sclerosis and Crohn’s disease in 2004. The drug was removed from the market after it was linked to three cases of PML but after a lengthy safety review was returned to the US market in 2006 under a special prescription program

--Roche’s Cellcept is a powerful immune suppressant used primarily to prevent transplant rejections. The FDA announced last year that it was investigating the link between the drug and PML after 16 patients developed the disease.

--Rituxan, co-marketed in the US by Genentech and Biogen Idec, is used for the treatment of B cell non-Hodgkins lymphoma, B-cell leukemias, and autoimmune disorders. The FDA issued a public health waning in December 2006 after receiving reports of two patients who develop PML and died while being treated with the drug for systemic lupus erythematosus.

Drug experts do not expect the withdrawal of Raptiva to affect any of the other drugs because the benefits for their indicated use far outweigh the risks of PML.

Both Genentech and the FDA have advised patients taking Raptiva to consult their physicians before stopping usage because abrupt withdrawal could lead to complications. The gradual withdrawal from the market is designed to give patients and physicans’ time to phase out the use of Raptiva and find alternative treatment.

Patients are also advised to check with their physicians immediately if they show any signs of PML, which include changes in thinking balance, strength, walking, and vision.

They should also consult a lawyer if they show any of these symptoms. Some legal experts anticipate a rash of Raptiva lawsuits because a recent Supreme Court ruling, Wyeth v. Levine, upheld the right of a person injured by a drug to sue the manufacturer even though the FDA had overseen and approved the drug’s warning label.