Psoriasis is an autoimmune skin disorder characterized by inflamed scaly patches. Alefacept is a fully human recombinant fusion protein that binds to the CD2 receptor on memory-effector T lymphocytes, inhibiting their activation. Psoriatic plaques are known to be heavily infiltrated with these so-called CD45RO+ cells, and this CD2 pathway plays a critical role in the pathogenesis of psoriasis, says Biogen's vice president of medical research Gloria Vigliani. The antibody also acts by binding to natural killer cells, causing apoptosis of memory-effector T cells and thinning out the crowds of these cells that gather in psoriatic plaques. This is believed to be alefacept's primary inflammation-reducing mechanism. It is also probably the reason why the resulting remissions can last as long as eight months.
Until recently, antibodies developed to treat the disease have shown little improved activity over placebo in trials, especially since the FDA has insisted on setting a hard-to-achieve primary endpoint called “PASI 75,” a 75% improvement in the psoriasis area and severity index (PASI). Biogen is aiming for approval of both intravenous and intramuscular versions of the drug, and has submitted data from two phase 3 studies of 500 patients each. About a third of the patients showed improvements of 75% or more in their PASI score. More than half showed a 50% reduction, which, according to Alice Gottlieb, director of the Clinical Research Center and professor of medicine at Robert Wood Johnson Medical School (New Brunswick, NJ), is “very satisfactory to most patients.” The data “demonstrate efficacy,” says Gottlieb, an expert on the biological treatment of psoriasis.
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