ZymoGenetics, Inc, (SEATTLE, Wash) announced preliminary positive findings from two phase Ib clinical trials in patients with systemic lupus erythematosus (SLE) treated with atacicept (formerly referred to as TACI-Ig). The results demonstrated a favorable tolerability profile and indicated biological activity consistent with the mode of action.

The primary objective of these two phase Ib clinical studies was to determine the safety and tolerability of atacicept administered subcutaneously or intravenously to patients with SLE. Secondary objectives included examination of the relationship between the atacicept dose and schedule with markers of biologic activity and disease activity. In both studies, atacicept appeared to be well tolerated across all dose levels and schedules tested in both studies, and clear biologic response corresponding to the mechanism of action of atacicept was observed.

Both clinical studies were multi-center, double-blind, randomized, placebo-controlled, dose-escalating studies. In the subcutaneous administration study, 49 patients were enrolled and patient cohorts received single or repeated doses (4 weekly doses) of atacicept or placebo. In the study with intravenous administration, 24 patients were enrolled and patient cohorts received single or repeated doses (2 doses, 21 days apart) of atacicept or placebo. All patients were monitored during and for several weeks after for safety.

ZymoGenetics and its partner, Serono SA, plan to start a phase II study of atacicept later in 2006 in rheumatoid arthritis (RA) patients with an inadequate response to TNF inhibitors.

Atacicept is a soluble, recombinant fusion protein (formed between the extracellular, ligand-binding domain of a novel cytokine receptor, human TACI (transmembrane activator and CAML [calcium-modulator and cyclophilin ligand]-interactor), and the Fc domain of human IgG that neutralizes BLyS (B-Lymphocyte Stimulator, also known in the literature as zTNF4, BAFF, TALL-1 and THANK) and APRIL (A Proliferation-Inducing Ligand), TNF family cytokines that promote normal and autoimmune B-cell maturation, proliferation and survival. Levels of BLyS and APRIL are elevated in patients with SLE, RA, and B-cell malignancies. Atacicept has been shown to affect several stages of B-cell development and may inhibit the survival of cells responsible for making antibodies.

— A. Techman