Chelsea Therapeutics Reports Subgroup Analysis of 44 Parkinson's Patients in Study 302 Shows Highly Statistically Significant Benefits of Droxidopa Therapy

Update: Northera (droxidopa) Now FDA Approved for Neurogenic Orthostatic Hypotension - February 18, 2014

CHARLOTTE, N.C., Dec. 14, 2009 (GLOBE NEWSWIRE) -- Chelsea Therapeutics International, Ltd. (Nasdaq:CHTP) announced that new data from a subgroup analysis of the 44 Parkinson's Disease (PD) patients enrolled in Study 302, a Phase III withdrawal study of Droxidopa for the treatment of symptomatic neurogenic orthostatic hypotension (NOH), demonstrated a more robust response compared to the overall study population. Study investigators presented these data during a symposium at the XVIII WFN World Congress on Parkinson's Disease and Related Disorders in Miami.

Study 302 evaluated the efficacy and safety of Droxidopa, a pro-drug that results in increased body stores of norepinephrine, in 101 patients with symptomatic NOH. All patients in Study 302 were evaluated for functional and symptomatic improvement through multiple endpoints including the orthostatic hypotension questionnaire (OHQ). The OHQ is a global measure of disease activity consisting of a two-part questionnaire that includes the six-item orthostatic hypotension symptom assessment scale (OHSA) and the four-item orthostatic hypotension daily activities scale (OHDAS), along with corresponding OHSA, OHDAS and OHQ composite scores.

Results from this subgroup analysis demonstrate that PD patients, all of whom were on concomitant Levodopa/dopa-decarboxylase inhibitors, showed the strongest therapeutic response to Droxidopa. PD patients receiving Droxidopa showed improvement over placebo on 9 of the 10 individual items of the OHQ as well as all 3 composite measures.

On the four question OHDAS, the 44 PD patients on Droxidopa demonstrated a statistically significant improvement in their ability to perform activities of daily living that require standing for a short period of time (p<0.05), standing for a long time (p<0.01), and walking for a short time (p<0.05). This compares to the 101 total patients that only reported statistically significant improvements in activities that require standing for a short time (p<0.05) and standing for a long time (p<0.05).

The marked improvements observed across each of the individual OHDAS variables resulted in a highly significant benefit as measured by both the OHDAS composite (p<0.005) and the OHQ composite (p=0.005) scores for PD patients receiving Droxidopa in Study 302.

"To achieve such highly statistically significant results on these efficacy measures in a sub-group of only 44 patients provides substantial evidence for the magnitude of Droxidopa's therapeutic benefit in patients with Parkinson's disease," said Christopher Mathias, D Phil, DSc, FRCP, FMedSci. Professor of Neurovascular and Autonomic Medicine, Imperial College London, St. Mary's Hospital and the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK and a principal investigator of the trial. "Further, the data from this study confirm that concomitant use of dopamine decarboxylase inhibitors, a mainstay of Parkinson's treatment, does not inhibit the beneficial effect of Droxidopa. This suggests that Droxidopa can be easily integrated into a patient's existing Parkinson's treatment program without affecting its therapeutic benefits or the benefits of existing therapies."

Parkinson's disease is the second most common neurodegenerative disorder in America. As a result of decreased levels of norepinephrine associated with PD, up to an estimated 20% of these patients may experience NOH symptoms associated with the disease or as a complication of medication. NOH is a neurogenic disorder resulting from deficient release of norepinephrine, the neurotransmitter used by sympathetic autonomic nerves to send signals to the blood vessels and the heart to regulate blood pressure. This deficiency results in decreased blood pressure when a person assumes a standing position and is characterized by lightheadedness, dizziness, and syncope. Symptoms of chronic NOH can be incapacitating -- not only putting patients at high risk for falls and associated injuries -- but also severely affecting the quality of life of patients and their loved ones, and generating significant health care costs. The only FDA-approved treatment for orthostatic hypotension has a black box warning indicating that the drug has not been shown to be effective in alleviating the symptoms of the condition and is associated with a pronounced side-effect profile including significant supine hypertension.

About the Study and Droxidopa Registration Program in NOH

Study 302, a Phase III trial of Droxidopa for the treatment of symptomatic NOH, was a double-blind, placebo controlled withdrawal-design study in which all patients underwent an initial open-label dose titration. Patients demonstrating both a symptomatic benefit and blood pressure improvement following titration continued on open-label Droxidopa for a 1-week run-in period prior to being randomized on a 1:1 basis to continue on active drug or be withdrawn to placebo. Results from this previously reported trial demonstrated Droxidopa's therapeutic benefit over placebo on 16 out of the study's 17 symptomatic and functional outcome variables, five of which achieved statistical significance (p<0.05).

About Droxidopa

Droxidopa, the lead investigational agent in Chelsea Therapeutics' broad pipeline, is currently in Phase III clinical trials for the treatment of symptomatic neurogenic orthostatic hypotension (NOH) in patients with primary autonomic failure - a group of diseases that includes Parkinson's disease, multiple systems atrophy (MSA) and pure autonomic failure (PAF). Droxidopa is a synthetic catecholamine that is directly converted to norepinephrine (NE) via decarboxylation, resulting in increased levels of NE in the nervous system, both centrally and peripherally. Droxidopa is also being studied for the treatment of fibromyalgia in an ongoing phase II trial and completed a phase II trial in intradialytic hypotension (IDH) study with positive results.

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, 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 our need to raise operating capital, our history of losses, risks and costs of drug development, risk of regulatory approvals, our reliance on our lead drug candidates Droxidopa and CH-1504, 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.

-0- CONTACT: Chelsea Therapeutics Investors: Kathryn McNeil 718-788-2856 mcneil@chelseatherapeutics.com

Hill & Knowlton Media: Sean Leous 212-885-0549 sean.leous@hillandknowlton.com

Posted: December 2009

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