Additional Analysis Confirms Significant Symptomatic Benefit of Droxidopa in Treatment of Neurogenic Orthostatic Hypotension

CHARLOTTE, N.C., Oct. 1, 2009 (GLOBE NEWSWIRE) — Chelsea Therapeutics International, Ltd. (Nasdaq:CHTP) announced that continued analysis of previously reported results from Study 302, the first of two pivotal Phase III trials in Chelsea’s registration program of Droxidopa for the treatment of symptomatic, neurogenic orthostatic hypotension (NOH), confirm statistically significant benefits across five clinically relevant assessment criteria that reflect symptomatic improvements and corroborate other supportive symptom data. The collective dataset also supports the exceptional safety and tolerability of Droxidopa.

“We are encouraged by the breadth and depth of findings from Study 302 that demonstrate a symptomatic benefit and provide validation of the safety and tolerability of Droxidopa for the treatment of neurogenic orthostatic hypotension — a serious condition with an urgent need for improved treatments,” said Dr. Simon Pedder, president and CEO of Chelsea Therapeutics. “In looking ahead, we believe these results will be evident in the results of Study 301 expected this quarter. Further, we believe the outcome of Study 301 may be enhanced by the washout period included in that study. This belief is supported by open-label data from Study 301 that demonstrate a marked return of symptoms prior to randomization. The increase in average dizziness score from 1.0 following dose titration to 5.4 after a 7-day washout period in Study 301 suggests a reduction in the carry-over effect that appeared to follow sustained drug treatment prior to randomized withdrawal in Study 302.”

Statistically Significant Symptomatic Benefit on Multiple Endpoints

Patients randomized into this double-blind, placebo controlled study were evaluated for functional and symptomatic improvement through multiple secondary endpoints including a clinician-recorded and patient-recorded clinical global impressions-severity (CGI-S) scale and the orthostatic hypotension questionnaire (OHQ), a two part questionnaire consisting of the six-item orthostatic hypotension symptom assessment scale (OHSA) and the four-item orthostatic hypotension daily activities scale (OHDAS).

With the exception of vision, Droxidopa demonstrated a marked improvement over placebo for each of the five other symptoms measured by the OHSA (dizziness, weakness, fatigue, concentration, and head/neck pain) with the overall composite OHSA score supporting the benefit of Droxidopa over placebo. Despite indicating an improvement over placebo, Item 1 on the OHSA (dizziness), the primary endpoint in the study, did not achieve statistical significance.

On the OHDAS, a measure of patient function which asks patients to evaluate the average impact of orthostatic hypotension on their daily lives over the prior week period using an 11-point scale, Droxidopa demonstrated a statistically significant improvement in activities that require standing for a short time (p=0.043), standing for a long time (p=0.023) as well as a statistically significant improvement in the composite OHDAS score (p=0.029) which includes evaluation of standing and walking for both short and long times.

Notably, in addition to symptomatic and functional benefits registered on the OHQ, Droxidopa demonstrated statistically significant improvement on both the clinician-recorded (p=0.045) and patient-recorded (p=0.008) CGI-severity scale, a widely accepted scale that asks clinicians and patients to rate the severity of a patient’s symptoms at the time of assessment.

“No other drug treatment has successfully demonstrated a statistically significant symptomatic and/or functional benefit in treating orthostatic hypotension,” commented Dr. Art Hewitt, Vice President of Drug Development at Chelsea Therapeutics. “By achieving statistical significance on five secondary endpoints that reflect both a functional and symptomatic benefit, three of which were specifically developed for this indication, Droxidopa has clearly demonstrated its unique ability to meaningfully treat symptomatic neurogenic orthostatic hypotension. We look forward to discussing these results with the FDA, as we believe that results from Study 302 provide meaningful data supporting Droxidopa’s efficacy and want to ensure we are taking all appropriate and actionable steps to ensure a successful NDA filing.”

Proven Safety and Tolerability

As previously reported, Droxidopa proved to be safe and well tolerated at all dose levels, with no significant adverse events or treatment related withdrawals in the Droxidopa arm.

Of the 101 patients evaluated in Study 302 (50 Droxidopa/51 Placebo), an equal number of patients on Droxidopa and placebo, 13 (26%), experienced at least one instance of supine systolic blood pressure (SBP) >160 mmHg; six (12%) of Droxidopa patients experienced supine SBP >180 mmHg vs. four (8%) on placebo. No patients treated with Droxidopa experienced supine hypertension >200 mmHg compared to one (2%) patient on placebo. These findings, in light of the inherent prevalence of supine hypertension in patients with primary autonomic failure, demonstrate that treatment with Droxidopa does not meaningfully alter the incidence of supine hypertension in the patient group. In the product labeling for Midodrine, the only approved compound for the treatment of orthostatic hypotension, supine hypertension (> 200 mmHg) is reported at 13.4%.

In addition, treatment with Droxidopa demonstrates a dramatic improvement in the incidence of falls associated with orthostatic hypotension. In Study 302, six (12%) patients on placebo reported falling at least once during the 14-day treatment period compared to one (2%) patient in the Droxidopa arm. This marked reduction in falls, while recorded under adverse events for the study, further supports the significant symptomatic benefit experienced by patients treated with Droxidopa.

NOH Impacts Quality of Life, Increases Health Care Costs

Neurogenic orthostatic hypotension 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.

An estimated 300,000 patients suffer from chronic symptomatic NOH in the U.S. and the EU. Symptoms of chronic NOH can be incapacitating — not only putting patients at high risk for falls and associated injuries — but also severely impacting the quality of life of patients and their loved ones, and generating significant health care costs. The only current FDA-approved treatment for orthostatic hypotension has not been shown to be effective in alleviating the symptoms of the condition and is limited in its use by a pronounced side-effect profile.

About Droxidopa and the Droxidopa Registration Trial in NOH

Currently available in Japan and with 15 years of safety and efficacy data, Droxidopa is the first drug to demonstrate symptomatic improvement of NOH. As an orally active synthetic precursor of norepinephrine, Droxidopa increases the supply of norepinephrine available for delivery to its receptors, effectively targeting the root cause of NOH to improve orthostatic blood pressure and alleviate symptoms of orthostatic hypotension.

The Droxidopa Phase III registration program in NOH includes two double-blind, placebo-controlled studies: Study 301 and Study 302. Study 301was reviewed by the U.S. Food and Drug Administration (FDA) and awarded a Special Protocol Assessment (SPA). An SPA provides a binding agreement that the study design, including trial size, clinical endpoints and/or data analyses is acceptable to support regulatory approval. In addition to the SPA, the FDA has awarded Chelsea Fast Track designation for its pivotal program in NOH. Fast Track designation is designed to facilitate the review of products that address serious or potentially life-threatening conditions for which there is an unmet medical need and provides the option to file a New Drug Application (NDA) on a rolling basis. This permits the FDA to review the filing as it is received, expediting the review process.

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), currently the leading antifolate treatment and standard of care for a broad range of abnormal cell proliferation diseases including RA.

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.