Vertex drops lead p38 MAP kinase inhibitor

Vertex Pharmaceuticals has terminated the clinical development of itslead p38 MAP kinase inhibitor targeting inflammatory diseases, including rheumatoid arthritis, and says it will now devote its resources to two second-generation follow-up compounds. The lead candidate, VX-745, has been dropped because of adverse effect findings in animal testing; in one of two animal species exposed to high doses of VX-745, worrisome side effects within the central nervous system were noted, according to the company.

The enzyme targeted by the drugs is thought to play a role in the synthesis of two key pro-inflammatory cytokines, tumor necrosis factor-alfa and interleukin-1, and Vertex claims to have a leading position in the p38 inhibitor field.

The finding is a disappointment to the firm, which had already completed a Phase II trial of VX-745 in RA patients which had already provided preliminary evidence that an orally-active drug in this class could have significant clinical effects, measured by American College of Rheumatology criteria, with no evidence of any neurological side effects. Based on the animal data, Vertex has elected not to to proceed with enrollment in a higher-dose cohort, and has also terminated a second ongoing study in myelodysplastic syndrome.