ZymoGenetics, Inc (SEATTLE, Washington) owns a diverse pipeline of product candidates that are moving into and through clinical development for autoimmune diseases, bleeding, and cancer. The company announced that its partner Merck Serono Intl has received agreement from the US FDA regarding a Special Protocol Assessment (SPA) for a phase II/III trial with atacicept in patients with general systemic lupus erythematosus (SLE). With a previously announced agreement from the FDA for a phase II/III study in lupus nephritis, which was initiated in December 2007, these studies are intended to support an application for marketing authorization of atacicept in the US for the treatment of SLE.

The randomized, double-blind, placebo-controlled, multicenter clinical trial will be conducted internationally and will evaluate approximately 500 patients with general SLE. The trial will evaluate the efficacy and safety of atacicept compared with placebo in the prevention of SLE flares. The primary efficacy endpoint will be the proportion of subjects experiencing a new flare during the 52-week treatment period following randomization.

Merck Serono is the sponsor for both clinical studies, and will conduct the general SLE trial. ZymoGenetics will operationally conduct the lupus nephritis study.

In the SPA process, the FDA evaluates the design of a clinical trial that will form the basis of an efficacy claim to support a new drug application. The SPA provides a binding agreement between the FDA and a company that the study design, trial size, endpoints, and data analyses plan, are acceptable to the FDA and would provide certain data to support a marketing application in the US.

ZymoGenetics and Merck Serono, an affiliate of Merck KGaA, in Darmstadt, Germany, are developing atacicept (formerly TACI-Ig) for the treatment of autoimmune diseases and B-cell malignancies. Atacicept contains the soluble TACI receptor that binds to the cytokines BLyS and APRIL. These cytokines are members of the TNF family that promote B-cell survival and autoantibody production associated with certain autoimmune diseases such as SLE. Current data indicates that levels of BLyS and APRIL are elevated in patients with rheumatoid arthritis, SLE, 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.