Synta Pharmaceuticals Corp, of Lexington, Massachusetts, announced that the first patients have been dosed in two separate phase IIa clinical studies of its lead immunomodulatory compound, apilimod mesylate (STA-5326), in rheumatoid arthritis (RA) and common variable immunodeficiency (CVID).

Apilimod mesylate is a first-in-class small-molecule oral compound that selectively inhibits the production of the IL-12 protein family, which includes the cytokines IL-12 and IL-23, important regulators of the Th1 immune response implicated in major chronic inflammatory diseases, including Crohn's disease, RA, psoriasis, and multiple sclerosis. STA-5326 inhibits transcription so that production and secretion of IL-12/IL-23 is reduced, also preventing T-cell activation. Preclinical studies have shown substantial efficacy in models of Crohn's disease, RA, and multiple sclerosis.

The phase IIa RA trial is a randomized, placebo-controlled study of apilimod mesylate in combination with methotrexate. This biomarker-based study will assess the efficacy of the drug by examining its effect on synovial tissue, focusing on macrophage counts, which have been shown to correlate with anti-arthritic activity.

Apilimod mesylate is currently in a large multinational phase IIb trial for Crohn's disease. In May 2005, the company completed a phase IIa open-label study of STA-5326 in active Crohn's disease, which indicated that treatment with daily doses of >e;35 mg demonstrated clinically meaningful disease response and remission rates. STA-5326 also showed an acceptable safety profile. Based upon these results, the company initiated a phase IIb, placebo-controlled study in September 2005. A companion study is being conducted concurrently to evaluate biological markers of activity in Crohn's disease.

Synta decided not to pursue further development of STA-5326 in psoriasis based on the results of a phase IIa biomarker study and a phase IIb, placebo-controlled clinical study of STA-5326 in chronic plaque psoriasis.

— A. Techman