Chelsea Therapeutics International Ltd. Reports Results Of Phase II Trial Of CH-4051 In Rheumatoid Arthritis

Chelsea Therapeutics International Ltd. announced that a preliminary analysis of its dose-ranging exploratory Phase II trial of CH-4051, a non-metabolized antifolate, in patients with rheumatoid arthritis (RA) who experience an inadequate response to methotrexate (MTX) treatment indicates that CH-4051 did not demonstrate superior efficacy to methotrexate in the dose range evaluated. Using a modified intent-to-treat (ITT) population of 244 patients with a post-baseline efficacy assessment, the primary efficacy analyses utilized the hybrid American College of Rheumatology score (hACR) followed by the traditional ACR 20 (20% improvement in ACR criteria) to compare responses among patients treated with 0.3 mg (n=48), 1.0 mg (n=48) or 3.0 mg (n=49) of CH-4051 daily, 3.0 mg of CH-4051 daily in combination with a folate supplement (n=49) or 20.0 mg MTX weekly (n=50) with a folate supplement for 12 weeks following a two-week MTX-washout. At the end of the 12-week period, patients treated with MTX showed greater improvement in both mean hACR (38.4) and ACR20 response rate (56.0%) compared to patients treated with 0.3mg CH-4051, 1.0 mg CH-4051, 3.0mg CH-4051 or 3.0mg CH-4051 with folate supplement. CH-4051 was found to be safe and well tolerated in the study, with no dose-limiting toxicities or clear differences in the overall adverse event rate between the MTX (52.9%) and 0.3mg, 1.0mg and 3.0mg CH-4051 (38.0%, 42.9% and 30.0%) and 3.0mg CH-4051 plus folate (49.0%) treatment groups.