Merck Serono headquarters Credit: Merck Serono

The US Food and Drug Administration has issued a public health advisory on Genentech's psoriasis drug Raptiva following four cases and three confirmed deaths from progressive multifocal leukoencephalopathy (PML), a rare and usually fatal brain viral infection, in patients taking the drug for several years. In Europe and Canada, where the drug is marketed by Geneva-based Merck Serono and Serono of Mississauga, Ontario, respectively, regulators have taken Raptiva off the market, stating that the benefit did not justify the risk. This may be the last straw for Raptiva (efalizumab), a monoclonal antibody (mAb) directed against T-cell marker CD-11. “It's doomed,” says Eric Schmidt, biotech analyst with Cowen and Company of New York. Raptiva, developed by Genentech of S. San Francisco, California, received a black box warning in 2005, after several cases of hemolytic anemia and again, in October 2008, following the first PML case. “Fortunately for Genentech it's a minor drug,” garnering around $100 million annually, says Schmidt. Although Raptiva was the first biologic to reach the market for psoriasis, sales were quickly eclipsed by a trio of tumor necrosis factor-a inhibitors: Enbrel (etanercept) from Amgen of Thousand Oaks, California, Remicade (infliximab), from Centocor of Horsham, Pennsylvania and Humira (adalimumab), from Abbott of Abbott Park, Illinois. Centocor's mAb Stelara (ustekinumab), which targets IL-12 and IL-23, and recently approved in Europe, may further erode Raptiva's sales. This isn't the first time an immune modulating drug has been associated with PML. In 2005, the multiple sclerosis drug Tysabri (natalizumab) produced by Biogen-Idec of Cambridge, Massachusetts, and Elan of Dublin, a mAb targeting integrin, was voluntarily withdrawn from the market after two patients contracted PML; the companies later returned with a risk minimization plan. Whereas over 46,000 patients have taken Raptiva, only roughly 1,000 have been taking it for three years, hence the incidence of PML with Raptiva may be higher than with Tysabri (1 in 15,000). Michael Paranzino, head of the Psoriasis Cure Now of Kensington, Maryland, feels that banning Raptiva isn't warranted, especially as market leader Enbrel only relieves 50% of patients. “Before a ban, why not consider restrictions on continuous, multi-year use? Why not consider having it as a second- or third-try option if the experts are convinced there are other, first-line options that are safer?” According to senior manager at Genentech, Tara Cooper, the company is working with the FDA, possibly to develop a risk minimization plan.