CHARLOTTE, N.C., May 9, 2011 (GLOBE NEWSWIRE) -- Chelsea Therapeutics International, Ltd. (Nasdaq:CHTP) announced that an independent Data Safety Monitoring Board (DSMB) recently met to review patient safety data for Chelsea's Phase II trial of CH-4051 in rheumatoid arthritis (RA) and recommended that each on-going arm of the study continue as planned and that enrollment be initiated into the 3.0 mg dose groups of the trial.
"We are very encouraged that this DSMB review provided us with a recommendation to open enrollment into our high dose groups," commented Dr. Simon Pedder, President and CEO of Chelsea Therapeutics. "We believe this trial will validate earlier clinical and pre-clinical findings by demonstrating CH-4051 has superior efficacy to methotrexate while maintaining both improved safety and tolerability. There is significant market opportunity for an oral disease modifying agent that could be used as an important therapeutic alternative prior to or in combination with injectable biologics or other oral disease modifying agents. We are eagerly looking forward to the unblinded interim data from this trial next quarter and the full results during the second quarter 2012."
This trial was initiated with a staggered start wherein the first patients were randomized to receive either 0.3 mg or 1.0 mg of CH-4051 daily or 20 mg methotrexate (MTX) weekly in combination with a folate supplement. The DSMB conducted its first review of safety data after 10 patients had completed treatment in both the 0.3 mg and 1.0 mg CH-4051 cohorts. As the DSMB reviewed the safety data and found no signals that preclude proceeding to the 3.0 mg dose, the study will begin randomizing patients into all five study cohorts.
Going forward, patients in this five-arm Phase II trial will now be randomized to receive 0.3 mg, 1.0 mg or 3.0 mg of CH-4051 daily, 3.0 mg of CH-4051 daily in combination with a folate supplement or 20 mg MTX weekly with a folate supplement for 12 weeks following a two-week MTX-washout.
The primary efficacy analysis will be conducted using the hybrid American College of Rheumatology score (hACR), which allows for a more comprehensive assessment of treatment benefit across all seven symptomatic and functional components of the standard ACR 20/50/70 evaluations historically used in RA trials.
Having already enrolled more than 100 patients into the two lower dose groups and MTX control arm, Chelsea intends to conduct an un-blinded interim efficacy analysis in the third quarter of 2011. Based on current enrollment, this unblinded interim analysis is expected to include the completion of greater than 90% of patients to be enrolled in the 0.3 mg and 1.0 mg cohorts. Full study results, inclusive of all dose groups, are expected in the second quarter of 2012.
As previously reported, 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 expected to be effective for multiple autoimmune disorders. The 5mg dose was as well tolerated as placebo. No serious adverse events occurred during the Phase I study and pharmacokinetic data indicated dose proportionate increases in plasma levels of CH-4051. Furthermore, it was revealed that plasma concentrations in the study were comparable to those seen in animal pharmacology studies in which CH-4051 demonstrated superior suppression of RA than both the maximally tolerated dose of methotrexate and equivalent doses of CH-1504.
About CH-4051
CH-4051 is the L-isomer of CH-1504 and second drug candidate from Chelsea's portfolio of orally bioavailable, non-metabolized antifolates. Both are orally available molecules with anti-inflammatory, autoimmune and anti-tumor properties that potently inhibit dihydrofolate reductase, an enzyme required for cell proliferation. Preclinical and clinical data to date suggests superior safety and tolerability, as well as increased potency versus MTX, currently the leading antifolate treatment and standard of care for a broad range of abnormal cell proliferation diseases. Diseases that may potentially be treated with these compounds include rheumatoid arthritis, psoriasis, Crohn's disease, ankylosing spondylitis, uveitus, psoriatic arthritis and several different kinds of cancer.
About Chelsea Therapeutics
Chelsea Therapeutics is a biopharmaceutical development company that acquires and develops innovative products for the treatment of a variety of human diseases. Chelsea's most advanced drug candidate, NORTHERA™ (droxidopa), is an orally active synthetic precursor of norepinephrine initially being developed for the treatment of neurogenic orthostatic hypotension. In addition to Droxidopa, Chelsea is also developing a portfolio of metabolically inert oral antifolate molecules engineered to have potent anti-inflammatory and anti-tumor activity to treat a range of immunological disorders, including two clinical stage product candidates: CH-1504 and CH-4051. Preclinical and clinical data suggest superior safety and tolerability, as well as increased potency versus methotrexate (MTX).
This press release contains forward-looking statements regarding future events. These statements are just predictions and are subject to risks and uncertainties that could cause the actual events or results to differ materially. These risks and uncertainties include risk of regulatory approvals, including our planned NDA for Northera; risks and costs of drug development, including the uncertainty of cost, timing and outcome of clinical trials like Study 306; our reliance on our lead drug candidates Droxidopa and CH-4051; our need to raise operating capital; our history of losses; reliance on collaborations and licenses; intellectual property risks; competition; market acceptance for our products, if any are approved for marketing; and reliance on key personnel including specifically Dr. Pedder.