The U.S. Food and Drug Administration (FDA) has requested additional information related to Chelsea Therapeutics’ Phase 2 trial of CH-4051 in rheumatoid arthritis (RA). The FDA is requesting additional detail from Chelsea’s preclinical studies, notably histological reports from lower dose groups in the completed toxicology studies, to establish the no-observable-adverse-effect-level (NOAEL) in this animal model and support proposed Phase 2 doses.
“Given the known toxicities and side-effects of methotrexate, the most widely prescribed antifolate, we believe that the FDA is interested in fully characterizing the safety of our proposed Phase 2 doses of CH-4051,” commented Dr. Simon Pedder. “It is, in part, why we believe there exists a significant need for both a safer and more effective antifolate treatment alternative. The purpose of the new proposed trial is to test if the safety and efficacy of CH-4051 will show improved tolerability and reduced hepatotoxicty as compared to the MTX.”
Chelsea anticipates completion of the requested histology reports by late July. In the interim, the company continues to explore potential strategies for further mitigating any FDA concerns regarding dose while allowing for evaluation of the full dose range and minimizing potential program delays. Chelsea anticipates filing a response to the FDA in late July, at which time the agency will have 30 days to review and respond to the submission.
Results from Chelsea’s Phase I single and multiple ascending dose studies demonstrated that CH-4051 was well tolerated at doses up to and including 7.5mg, a dose range likely to be effective for multiple autoimmune disorders. The 5mg dose was as well tolerated as placebo. High doses of CH-4051 demonstrated mostly mild toxicities, with the 10mg and 20mg doses groups reporting both gastrointestinal side-effects and reversible liver enzyme elevations. No serious adverse events occurred during the study. Chelsea’s proposed Phase II trial of CH-4051 is intended to evaluate up to 3.0 mg daily oral doses of CH-4051 in a 12-week, head-to-head study against 20.0 mg weekly oral doses of methotrexate in rheumatoid arthritis patients that have previously demonstrated an inadequate response to methotrexate treatment.
Date: June 29, 2010
Source: Chelsea Therapeutics
June 9, 2010 Announcement
Filed Under: Drug Discovery
