ZymoGenetics, Inc, (SEATTLE, Wash.) and Serono (GENEVA, Switzerland) announced results from an exploratory dose-escalating, single- and repeat-dose phase Ib clinical trial with TACI-Ig (atacicept) in 73 adult patients with active, moderate-to-severe rheumatoid arthritis (RA). The patients in this multi-center, randomized, double-blind, placebo-controlled trial received subcutaneous administration of single or multiple doses of either TACI-Ig or placebo for a maximum period of 3 months. TACI-Ig appeared to possess a favorable safety and tolerability profile and demonstrated exposure-dependent biological activity in line with its mechanism of action, including up to a 30-40% reduction in the levels of total and mature B-cells, and reduced immunoglobulin (IgM, IgA, and IgG) and rheumatoid factor. There were also positive trends of effect on disease activity/progression (ACR 20, DAS 28). ZymoGenetics and Serono expect to begin a phase II clinical trial of TACI-Ig in patients with RA in the second half of 2006.

TACI-Ig is a soluble, recombinant fusion protein (formed between the extracellular, ligand-binding domain of the human TACI receptor and the Fc domain of human IgG) that neutralizes BLyS and APRIL, TNF family cytokines that promote normal and autoimmune B-cell maturation, proliferation, and survival. Levels of BLyS and APRIL are elevated in patients with RA, systemic lupus erythematosus, and B-cell malignancies. TACI-Ig has been shown to affect several stages of B-cell development and may inhibit the survival of cells responsible for making antibodies.