ZymoGenetics, Inc. announced that, together with its collaborator Merck Serono, it has reached an agreement with the US Food and Drug Administration (FDA) on a Special Protocol Assessment (SPA) to conduct a pivotal clinical trial with the investigational new drug Atacicept for the treatment of patients with lupus nephritis.

According to a company press release, this is one of two clinical studies intended to form part of the application for marketing authorization. The randomised, double blind placebo-controlled multi-centre clinical trial will be conducted at sites in North America, Europe, Latin America, and Asia. Approximately 200 patients with active lupus nephritis will be enrolled in this trial, aimed at demonstrating the efficacy and safety of Atacicept as compared to placebo.

"Together with Merck Serono, we concluded that an SPA provided the clearest path to ensure that this trial will support the application for Atacicept marketing authorization. We're pleased to have reached agreement with the FDA about the design of this study and plan to begin enrolling patients in the fourth quarter of 2007," said Nicole Onetto, M.D., senior vice president and chief medical officer, ZymmoGenetics.

In the SPA process, the FDA evaluates the design of clinical trials intended to 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 are adequate to support a license application for marketing in the US

ZymoGenetics and Merck Serono are developing Atacicept as a potential treatment for autoimmune diseases and B-cell malignancies. Merck Serono is the study sponsor, however ZymoGenetics will operationally conduct the lupus nephritis study. The companies plan to conduct a second study in patients with general systemic lupus erythematosus, for which the SPA review process is ongoing.

Lupus nephritis is a complication of systemic lupus erythematosus (SLE) and is characterized by inflammation of the kidneys. Patients with lupus nephritis typically have damage to the glomerulus and progressive loss of kidney function. In the U.S., SLE affects 1 in 2000, with higher rates among women and among individuals with African, Asian, and Hispanic genetic heritage. According to the company data, clinical renal involvement occurs in at least 30 per cent of those with SLE.

ZymoGenetics and Merck Serono, an affiliate of Merck KGaA, Darmstadt, Germany, are developing Atacicept (formerly referred to as 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 tumour necrosis factor family that promote B-cell survival and auto antibody 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.

ZymoGenetics creates novel protein drugs with the potential to significantly help patients fight their diseases. The company is developing a diverse pipeline of product candidates that are moving into and through clinical development. These candidates span a wide array of clinical opportunities that include bleeding, autoimmune diseases, and cancer. ZymoGenetics intends to commercialise these product candidates through internal development, collaborations with partners, and out-licensing of patents from its extensive patent portfolio.