Merck KGaA (DARMSTADT, Germany) announced that its Merck Serono division and development partner ZymoGenetics, Inc have initiated a phase II/III trial of atacicept (formerly TACI-Ig) in patients with systemic lupus erythematosus (SLE). The mechanism of action of atacicept, inhibiting the two growth factors BLyS and APRIL that are known to impact disease progression, is the basis for studying atacicept in SLE.

The study is being conducted under a Special Protocol Assessment (SPA) agreement with the US FDA (Food and Drug Administration), in which the agency evaluates the design of a clinical trial that will form the basis of an efficacy claim to support a new drug application. Unless the FDA identifies a substantial scientific issue essential to determining the safety or effectiveness of the drug after testing has begun, the SPA provides a binding agreement that the study design, trial size, endpoints, and data analyses plan are acceptable to the FDA and would provide certain data needed to support a license application for marketing in the US.

A second phase II/III study in lupus nephritis (LN) was initiated in December 2007. Collectively, the two studies are intended to form part of a potential registration package to support worldwide applications for marketing authorization.

The 52-week, randomized, double-blind, placebo-controlled, international phase II/III clinical trial will enroll ~500 SLE patients and will evaluate the efficacy and safety of atacicept compared with placebo in preventing SLE flares. The primary efficacy endpoint is the proportion of subjects experiencing a new disease flare, based on BILAG (British Isles Lupus Assessment Group) measurements. The advantage of using BILAG compared with other assessment methods is that it allows each organ system to be evaluated.

Atacicept, a recombinant fusion protein, contains the soluble TACI receptor that binds to the cytokines, BLyS and APRIL, which are members of the TNF family that promote B-cell survival and autoantibody production associated with certain autoimmune diseases such as SLE. Current data indicate that BLyS and/or APRIL levels are elevated in patients with rheumatoid arthritis (RA), SLE, multiple sclerosis (MS), and B-cell malignancies. Thus, in addition to SLE and LN, Merck Serono and ZymoGenetics are codeveloping atacicept as a potential treatment of RA, MS, and B-cell malignancies. Under the terms of the codevelopment and commercialization agreement with ZymoGenetics, Merck Serono has exclusive rights to market the drug globally except in North America where ZymoGenetics has the option to copromote the drug with Merck Serono.

Atacicept has been shown in animal models to affect several stages of B-cell development and may inhibit the survival of cells responsible for making antibodies.