* Data from Study 302 continued to demonstrate robust effect with mean reduction in symptomatic score of 4.2 units and increase of 25mmHg in standing systolic blood pressure * Preliminary analysis of similar data from Study 301 supports filing a protocol amendment to study 302 to tighten the standard deviation used to calculate the trial sample size from 3.0 to 2.5, thereby reducing the target number of randomized patients 118 to 82 patients
CHARLOTTE, N.C., Feb. 17, 2009 (GLOBE NEWSWIRE) -- Chelsea Therapeutics International, Ltd. (Nasdaq:CHTP) announced that the Company has completed a second analysis of data from the open-label titration portion of its Phase III Study 302 which demonstrated patients treated with Droxidopa, a synthetic precursor to norepinephrine, showed a similarly robust reduction in the severity of symptoms associated with neurogenic orthostatic hypotension (NOH) and a improvement standing systolic blood pressure as reported in November 2008.
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 4.2 units on Item 1 (dizziness or light-headedness) of the Orthostatic Hypotension Symptom Assessment Scale (OHSA) during titration and a mean improvement in standing systolic blood pressure (SBP) of 25 mmHg. The average baseline OHSA score for responders prior to treatment was 6.3 and the average score at the end of the titration was 2.1. 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.
In addition to the efficacy analysis of titration data from Study 302, Chelsea conducted a preliminary review of data from Study 301, a similarly designed concurrent Phase III trial of Droxidopa in NOH, and based on corroborating data from this analysis reviewed its statistical plan for Study 302. Consequently, Chelsea has opted to file an amendment to the trial protocol for Study 302 to allow for a standard deviation of 2.5 compared to the prior standard deviation of 3.0 used to calculate the trial size. As a result of this change to the standard deviation, the number of patients to be randomized in the trial would be reduced from 118 to 82 patients. The study, in evaluating up to 84 patients, would remain powered to detect a mean relative change of 1.6 units or greater on the OHSA scale between treatment and placebo groups with a standard deviation of 2.5.
"I am pleased to report that our second analysis of titration data from a larger patient set affirms the robust effect that we initially reported in November and, while the magnitude of response demonstrated during titration may not be predictive of final results, we remain confident that the trial is well-designed to demonstrate a statistically significant benefit in patients treated with Droxidopa," commented Dr. Simon Pedder, President and CEO of Chelsea Therapeutics. "I am also pleased that a review of our statistical plan for study 302 suggests we can adjust our standard deviation assumptions and consequently reduce the number of patients required to demonstrate statistical significance in our final study results. As is often the case for orphan indications, patient enrollment has been a critical factor in completion of our study and we expect this adjustment in trial size to be of significant benefit to the timely completion of our Phase III program. With our revised enrollment target for Study 302 and recruitment in both Phase III studies to date, we anticipate completing enrollment for both study 301 and 302 late in the second quarter of 2009 with data available in the third quarter and allowing for an NDA filing by year-end 2009 as planned."
Study 302 is one of two Pivotal Phase III trials comparing Droxidopa to placebo for the treatment of symptomatic neurogenic orthostatic hypotension. The other trial, Study 301, was reviewed by the U.S. Food and Drug Administration (FDA) and awarded a Special Protocol Assessment (SPA) in February 2008. 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 allows a company 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 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.