November 3, 2008
Chelsea Therapeutics Reports Significant Reduction in Severity of Symptoms During Titration Phase of Pivotal Droxidopa Study in Neurogenic Orthostatic Hypotension
* Responders Demonstrated Mean Reduction in Symptomatic Score of 4.6 Units and Increase of 27mmHg in Standing Systolic Blood Pressure
CHARLOTTE, N.C., Nov. 3, 2008 (GLOBE NEWSWIRE) -- Chelsea Therapeutics International, Ltd. (Nasdaq:CHTP) announced that data from the open-label titration portion of Chelsea's Phase III trial demonstrated patients treated with Droxidopa, a synthetic precursor to norepinephrine, showed a robust reduction in the severity of symptoms associated with neurogenic orthostatic hypotension (NOH) and a significant improvement standing systolic blood pressure.
In a presentation at the 19th International Symposium on the Autonomic Nervous System of the American Autonomic Society in Hawaii, Dr. Kaufmann, Felicia B. Axelrod Professor of Dysautonomia Research at NYU School of Medicine and a principle investigator for the study, reported data related to the first 35 patients to complete titration show a clear improvement across all doses of Droxidopa up to 600 mg t.i.d.Patients identified as responders during the open-label titration phase of the study, and therefore eligible for inclusion in the double-blind, randomized trial, demonstrated a mean improvement of 4.6 units on Item 1 (dizziness or lightheadedness) of the Orthostatic Hypotension Symptom Assessment Scale (OHSA) during titration. The average baseline score for responders prior to treatment was 6.4 and the average score at the end of the titration was 1.8. The OHSA scale is a validated scale designed to rate symptoms occurring specifically as a result of low blood pressure and uses an 11-point scale (zero to 10), with more severe symptoms scoring higher. The same measure will be used as the primary endpoint in the blinded study to determine the relative difference in symptomatic benefit between Droxidopa and placebo 14 days post-randomization. The study, evaluating up to 118 patients, is powered to detect a mean relative change of 1.6 units or greater between treatment and placebo groups with a standard deviation of 3.
In addition to significant symptomatic improvement, responders demonstrated a mean improvement in standing systolic blood pressure (SBP) of 27 mmHg. This improvement was achieved with only a modest impact on supine blood pressure, with mean standing SBP increasing 32.4% compared to only a 13.8% increase in mean supine SBP.
"Given the extensive body of existing clinical evidence supporting the efficacy of Droxidopa in the treatment of neurogenic orthostatic hypotension, it is not surprising to see the robust efficacy signal reflected in these data," commented Dr. Kaufmann. "However, the unique enrichment design of this trial has provided us with the first evidence of an individualized response between 100mg TID through 600 mg TID along with evidence that while Droxidopa has a significant impact on standing systolic blood pressure, patients have only a minimal increase in supine systolic blood pressure. Based on the findings to date, the titration to effect paradigm appears to be a rational and effective method for optimizing treatment in this diverse patient population. I look forward to continuing this clinical evaluation and confirming these preliminary findings in the full study results."
About Droxidopa and Symptomatic Neurogenic Orthostatic Hypotension (NOH)
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 suffer from chronic symptomatic NOH in the U.S. and EU combined. In addition to creating significant health care costs, symptomatic NOH has a dramatic impact on the quality of patient life. 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.
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 the development of the I-3D 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, 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.
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CONTACT: Chelsea Therapeutics Nick Riehle, Chief Financial Officer 704-973-4201 Kathryn McNeil, Investor/Media Relations 718-788-2856