Chelsea Therapeutics Announces Results of European Phase IIb Trial of Droxidopa

Trial Finds Droxidopa Statistically Significant in Reducing Fall in Orthostatic Systolic Blood Pressure

CHARLOTTE, NC, USA | Jan 11, 2007 |
Chelsea Therapeutics International, Ltd. (Nasdaq:CHTP) reported the preliminary results of a European Phase IIb trial of Droxidopa, an orally available synthetic amino acid for the treatment of neurogenic orthostatic hypotension.

The primary objective of the trial was to determine the optimal dose of Droxidopa in the treatment of orthostatic hypotension in patients with multiple system atrophy (MSA) or Parkinson's Disease (PD). The double-blind, randomized, placebo-controlled, parallel group, Phase IIb trial led by Christopher Mathias, D Phil, DSc, FRCP, Professor of Neurovascular Medicine, Imperial College School of Medicine at St. Mary's Hospital, London, was conducted at 30 centers in the EU and significantly expands the body of clinical data available in non-Asian populations. The trial consisted of 125 randomized patients with 121 patients enrolled in the intent to treat population for efficacy evaluation. Patients received either placebo or Droxidopa three times daily (tid) for 28 days in doses ranging from 100 mg to 300 mg.

Statistical significance in reducing the fall in orthostatic systolic blood pressure (SBP) was demonstrated at 300 mg tid with the difference in SBP being 11.6 mm Hg between the groups. Results of the trial further validated the excellent tolerability of Droxidopa, which exhibited no difference in the incidence or severity of adverse events or laboratory values when compared to placebo. Data from the trial further suggested that concomitant medications such as dopamine decarboxylase inhibitors, a mainstay in both PD and MSA therapy, did not limit the therapeutic benefit of Droxidopa.

"I am pleased to see the results of this trial confirm the expected safety at higher doses and efficacy of Droxidopa in treating a broad population," commented Dr. Christopher Mathias. "Of particular interest was our finding that therapeutic benefit was also demonstrated in patients taking dopamine decarboxylase inhibitors. Given the typically complex treatment programs for patients suffering from PD and MSA, the demonstrated efficacy of Droxidopa when administered in addition to these widely prescribed medications could have a beneficial impact on the possible therapeutic applications of Droxidopa. I look forward to confirming these findings in a Phase III trial and working with Chelsea in their future clinical investigation of Droxidopa."

"The results of this trial complement the already robust data compiled by DSP regarding the therapeutic benefit of Droxidopa in treating orthostatic hypotension," added Dr. Simon Pedder, President and CEO of Chelsea Therapeutics. "We anticipate that this additional data will be of significant use as we prepare our submissions for marketing approval to both the FDA and EMEA. We also eagerly look forward to assisting Dr. Mathias in the preparation of complete findings from this trial for possible publication and future presentation."

Chelsea acquired the global development and commercialization rights to Droxidopa, excluding Japan, Korea, China and Taiwan, through an exclusive license agreement with Dainippon Sumitomo Pharma Co., Ltd. (DSP) in May 2006. Following the execution of this licensing agreement, DSP made available to Chelsea data from a previously unreported European Phase IIb trial. This data has subsequently been shared with the trial's principal investigator and results analyzed, with cooperation from DSP, by Chelsea.

As part of its development strategy for Droxidopa, Chelsea filed an application for Orphan designation for the treatment of symptomatic neurogenic orthostatic hypotension in patients with Primary Autonomic Failure with both the FDA and EMEA. Based on discussions with the both agencies, Chelsea currently expects to receive a determination from the FDA later this month and from the EMEA late in March of 2007.

About Droxidopa and Symptomatic Neurogenic Orthostatic Hypotension

Symptomatic NOH is a neurogenic disorder resulting from a deficient release of norepinephrine, the neurotransmitter used by sympathetic autonomic nerves to send signals to the blood vessels and the heart. This deficiency results in decreased blood pressure when a person assumes a standing position and is characterized by lightheadedness, dizziness, blurred vision and syncope. Droxidopa, an orally active synthetic precursor of norepinephrine, increases the supply of norepinephrine available for delivery to its receptors to improve orthostatic blood pressure and alleviate symptoms of orthostatic hypotension.

Chelsea estimates that nearly 300,000 patients in the U.S. and EU combined suffer from chronic symptomatic neurogenic orthostatic hypotension (NOH) associated with Primary Autonomic Failure, a group of diseases that includes Parkinson's Disease, Pure Autonomic Failure and Multiple Systems Atrophy.

In addition to creating significant health care costs, symptomatic NOH has a dramatic impact on the quality of life for those patients suffering from Primary Autonomic Failure. Midodrine, currently the only FDA approved treatment for orthostatic hypotension, not only fails to treat the underlying cause of symptomatic NOH but is limited in its use by a pronounced side-effect profile and black box warning for supine hypertension. Given the chronic nature of symptomatic NOH and the proven safety and tolerability of Droxidopa, Chelsea expects that daily oral treatment with Droxidopa should provide a significant improvement in the long-term treatment of symptomatic NOH.

Droxidopa, developed by and licensed from Dainippon Sumitomo Pharma Co., Ltd. (DSP), initially received Japanese approval in 1989 for the treatment of frozen gait and dizziness on standing associated with Parkinson's Disease and for the treatment of orthostatic hypotension, syncope or dizziness on standing associated with Shy-Drager syndrome and Familial Amyloidotic Polyneuropathy. In 2000, Droxidopa received expanded marketing approval to include treatment of vertigo, dizziness and weakness associated with orthostatic hypotension in hemodialysis patients. Droxidopa has historically generated annual revenues of approximately $50 million in Japan.

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 pursuing an Orphan Drug strategy for the development of 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 data, 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, the need to acquire or develop additional products and the other risk factors set forth from time to time in our SEC filings.

SOURCE: Chelsea Therapeutics International, Ltd

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