CHARLOTTE, N.C., Jan. 23, 2008 (PRIME NEWSWIRE) -- Chelsea Therapeutics International, Ltd. (Nasdaq:CHTP) announced that it has initiated enrollment and patient dosing in a multinational, 12-week, double-blind Phase II trial designed to compare the efficacy and tolerability of CH-1504 against methotrexate (MTX) in rheumatoid arthritis (RA) patients.
CH-1504, a non-metabolized antifolate, is engineered to provide the same potent efficacy as MTX but without the side effects caused by the metabolic breakdown of MTX into by-products that are believed to play a significant role in the liver and kidney toxicities and tolerability related side effects associated with chronic therapy. In order to accurately compare the efficacy and tolerability profile and assess the suitability of CH-1504 as a first-line treatment alternative to MTX, the Phase II trial will be conducted in a MTX naive RA patient population.
The 4-arm, parallel group trial will enroll 200 patients and compare 0.25 mg, 0.5 mg and 1.0 mg once daily oral doses of CH-1504 to a 20 mg once weekly oral dose of MTX. The primary efficacy endpoint of this study is to determine the percent of patients with ACR 20 response at the end of 12 weeks. An ACR 20 response is a standard efficacy measure that requires at least a 20% improvement in a number of different measures of disease activity. As the improved safety and tolerability of CH-1504 is expected to be a significant advantage over MTX, the trial will also compare a cluster of gastrointestinal system related adverse events, such as nausea, vomiting, and diarrhea, frequently seen with MTX use as well as closely monitor the results of standard liver function tests across dose groups.
"Though MTX is considered the standard of care in RA, both as a monotherapy and in combination with a majority of biologic treatments, MTX use is limited by its well-documented tolerability issues and long-term toxicity concerns," commented Dr. Simon Pedder, Chelsea's President and Chief Executive Officer. "We believe there is a significant market opportunity for a better, safer version of methotrexate. This proof-of-concept trial represents an opportunity for us to not only demonstrate CH-1504's significant advantages over MTX but to also differentiate our compound from other disease modifying drugs, both approved and under development, whose safety and tolerability are limited by their combination use with MTX."
About CH-1504
CH-1504 is the lead product candidate in Chelsea's portfolio of novel antifolate compounds developed by Dr. Gopal Nair and licensed by the company in 2004. An orally available and metabolically inert antifolate with potent anti-inflammatory and anti-tumor properties, CH-1504 potently inhibits several key enzymes that are 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 benefit from the compound include RA, psoriasis, inflammatory bowel disease, cancer and other immunological disorders.
Chelsea reported positive preliminary results from its U.K. Phase I trials for all oral indications of CH-1504 in December 2005. Additionally, an independent six-month pilot clinical study compared CH-1504 to MTX in 20 RA patients in Peru. Although this pilot study will not be used as a part of the U.S. regulatory approval process, the results of this study suggest that CH-1504 has lower toxicity and improved tolerability, as well as potentially increased efficacy versus MTX. Preclinical animal models have also indicated that CH-1504 may have superior efficacy and a greater therapeutics window than MTX.
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. The Company is currently developing a library of metabolically inert antifolate compounds engineered to have potent anti-inflammatory and anti-tumor activity to treat a range of immunological disorders. Early clinical data suggests that Chelsea's lead antifolate compound, CH-1504, is a safe and effective treatment alternative to methotrexate for RA and may have further applications for psoriasis, IBD and certain cancers. Chelsea's antifolate program is complemented by a strategic partnership with Active Biotech AB for the joint development of a portfolio of therapeutics targeting immune-mediated inflammatory disorders and transplantation. In addition to its autoimmune pipeline, Chelsea is developing Droxidopa, an orally active synthetic precursor of norepinephrine, for the treatment of neurogenic orthostatic hypotension. Currently approved and marketed in Japan, Droxidopa has accumulated over 15 years of proven safety and efficacy, historically generating annual revenues of approximately $50 million in Japan.
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 reliance on collaborations and licenses, risks and costs of drug development, regulatory approvals, intellectual property risks, our reliance on our lead drug candidate CH-1504, our history of losses and need to raise more money, competition, market acceptance for our products if any are approved for marketing, reliance on key personnel including specifically Dr. Pedder, management of rapid growth, and the need to acquire or develop additional products.