Chelsea Therapeutics Granted MHRA Approval to Begin Phase II Trial of Droxidopa in
Company Anticipates Dosing First Patient in Late September
CHARLOTTE, N.C., July 23, 2008 -- Chelsea Therapeutics International, Ltd. (Nasdaq:CHTP) has received approval from the United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA) to begin a Phase II trial of Droxidopa, alone and in combination with carbidopa, for the treatment of Fibromyalgia.
Fibromyalgia is a chronic and debilitating condition that is characterized by widespread pain and stiffness throughout the body, accompanied by severe fatigue, insomnia and mood symptoms. While the precise etiology of fibromyalgia remains unknown, current research has focused on the role of norepinephrine (NE) reuptake and availability in the central nervous system. NE, a widely used neurotransmitter in the central and peripheral nervous systems has long been linked to both chronic pain and depression. Droxidopa, a synthetic amino acid, is converted by the body into norepinephrine and as a prodrug of NE, provides replacement therapy for NE deficiency. While NE, as a catecholamine does not penetrate the blood-brain barrier, droxidopa, as a neutral amino acid, is able to do so thus providing both a peripheral and central affect on circulating NE levels.
To evaluate the role of NE in fibromyalgia and the safety and efficacy of Droxidopa in this indication, Chelsea intends to conduct an exploratory Phase II trial of Droxidopa, both alone and in combination with carbidopa in 120 fibromyalgia patients. As a dopa decarboxylase inhibitor that does not cross the blood-brain barrier, carbidopa is expected to limit the peripheral metabolism of Droxidopa into NE before it crosses into the brain, thus promoting a greater central effect in those patients receiving combination therapy. In addition to promoting the central effect of Droxidopa, the addition of carbidopa may allow lower doses of Droxidopa to be used thus further reducing the risk of any potential side effects.
Chelsea intends to initiate a multi-centre, randomized, double-blind, placebo-controlled, dose response, factorial 12-arm parallel group Phase II trial in September. The 12-arm trial will evaluate 120 patients equally randomized to receive Droxidopa monotherapy, carbidopa monotherapy, Droxidopa/carbidopa combination therapy or placebo. Accordingly, 10 patients will be randomized into each of 12 groups to receive: 200mg, 400mg or 600 mg of Droxidopa TID; 25mg or 50mg carbidopa TID; 200/25mg, 400/25mg or 600/25mg Droxidopa/carbidopa TID; 200/50mg, 400/50mg or 600/50mg Droxidopa/carbidopa TID; or placebo over a 9-week treatment period. The primary endpoint will be the average reduction in pain as measured by the Short Form McGill Pain Questionnaire. Secondary outcomes of the study include Fibromyalgia Index Questionnaire (FIQ), Patient Global Impression of change (PGI-C), Multidimensional Fatigue Inventory (MFI), and Hamilton Anxiety Depression survey (HAMA). Results from this trial are expected to be available in 2010.
"This approval to begin Phase II clinical trials of both mono- and combination therapy in fibromyalgia is a tremendous step forward in our development of Droxidopa, as it as it enables us to begin our first clinical evaluation of Droxidopa in a new indication outside its existing Japanese label and begin to leverage the full potential of droxidopa in a broad range of indications in which norepinephrine deficiency may play a significant role," commented Dr. Simon Pedder, Chelsea's President and Chief Executive Officer. "Given the established role of norepinephrine in pain attenuation, recent clinical data suggesting the efficacy of SNRIs in treating fibromyalgia and the abundant preclinical data showing dose-dependant analgesia of Droxidopa in chronic pain, we are optimistic about the potential role Droxidopa could play in the multibillion dollar fibromyalgia market."
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.
Kathryn McNeil, Investor/Media Relations
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