Alefacept

Summary

Alefacept is a recombinant, dimeric fusion protein consisting of the extracellular, CD-2 recognition region of human LFA-3 (leukocyte function antigen-3, soluble portion) linked to human Fc IgG1. The resultant compound exerts an overall inhibitory effect on T cell activation via binding to CD2 on the surface of memory effector T-cells and blocking of their interaction with native LFA-3. In addition, T-cell depletion is thought to occur via Fc-mediated NK cell recognition. Immune modulation in psoriasis is proposed to occur via apoptosis of memory T cells, inhibition of T-cell costimulatory signaling, and decreased activity and infiltration of T-cell and dendritic cell subtypes [Gottlieb AB, 2005].

Alefacept received approval in the USA in 2003 for treatment of adults with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy. In two Phase III licensing trials consisting of 12 once-weekly intramuscular or intravenous administrations, significant responses as measured by Psoriasis Area and Severity Index scores (PASI 50 and PASI 75) occurred within and after the administration period. Additional disease remission benefit from multiple treatment courses has also been seen to occur.

CD4+ T-cell depletion occurs with alefacept treatment, and patients undergoing therapy require period monitoring of peripheral CD4+ T-cell counts. These counts, however, do not appear to correlate with clinical response. Additionally, delayed clinical responses to Alefacept occur due to mechanisms which remain unclear.

Brand Name

Amevive

Other Names

BG 9273

Molecular Target

CD2

Molecular Structure

LFA-3-IgG1 Fc fusion protein

Licensed Indication, Major Target Diseases

moderate to severe, chronic plaque psoriasis

Manufacturer

Astellas Pharma

Distributor

Biogen IDEC

References