Synta Pharmaceuticals announced that the first patients have been dosed in two separate phase 2a clinical studies of its lead immunomodulatory compound, apilimod mesylate (STA-5326), in rheumatoid arthritis (RA) and common variable immunodeficiency (CVID). Apilimod mesylate is a novel, oral, small-molecule 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 immune response implicated in major chronic inflammatory diseases, including Crohn's disease, RA, psoriasis, and multiple sclerosis. The IL-12 family has also been shown to be a critical factor in the pathogenesis of the gastrointestinal (GI) complications of CVID. Apilimod mesylate is currently in a large multinational phase 2b trial for Crohn's disease.
"Initiating additional trials in RA and CVID with apilimod mesylate represents another clinical milestone for Synta as we seek to expand the compound's clinical and market potential into new conditions in addition to Crohn's disease," Safi Bahcall, Synta's president and CEO said adding, "As the first and only potent and selective oral inhibitor of the IL-12 cytokine family, we believe that apilimod mesylate could be a valuable new treatment option for a number of chronic inflammatory diseases that are inadequately treated or lack oral therapies today."
The phase 2a 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. For the treatment of the GI manifestations of CVID, apilimod mesylate is being studied in a small open-label Phase 2a trial, in which tissue from patients will be examined in order to understand the direct impact of the compound on the GI tract.
"We are very enthusiastic about the clinical potential of apilimod mesylate, the first oral inhibitor of IL-12 and IL-23, in RA and CVID," said Eric Jacobson, VP & chief medical officer of Synta. "As a rheumatologist, I believe that many RA patients would prefer an oral small-molecule, disease-modifying agent for their disease over injectable protein-based treatments. RA is a devastating chronic disease that affects five million patients globally and three million patients in the US. Patients suffering from CVID also have unmet medical needs since there are no approved therapies for the GI manifestations of this serious orphan condition," he added.