Study Published in Neurology Shows Tetrabenazine Significantly Improves Debilitating Movement Disorder Caused by Huntington's Disease.

WASHINGTON -- First Drug to Seek U.S. Food and Drug Administration Approval for Chorea Associated with Huntington's Disease

New data show the investigational therapy tetrabenazine, at dosages adjusted to patient response and side effects, titrated up to 100 mg per day, significantly improved clinical outcomes and reduced symptoms of chorea associated with Huntington's Disease (HD), a debilitating neurological disorder marked by incessant involuntary movements for which there is no approved therapy in the United States.

Results of a double-blind, placebo-controlled, pivotal Phase III study were published in the February 14, 2006 issue of Neurology, the official journal of the American Academy of Neurology. In the study, the investigators concluded that tetrabenazine significantly reduced patients' chorea burden, improved global outcome scores, and was generally safe and well tolerated.

Tetrabenazine is a highly selective and reversible dopamine depletor that works by inhibiting vesicular monoamine transporter 2 (VMAT2). It is being developed in the U.S. by Prestwick Pharmaceuticals, Inc., which has filed a New Drug Application (NDA) to market the product under the trade name XENAZINE(TM). XENAZINE received an orphan drug designation, because it is targeted to a rare disease that affects fewer than 200,000 people, and also has been granted priority review under the Agency's fast track drug development program. The company's NDA is currently under review by the U.S. Food and Drug Administration (FDA).

Based in Washington, DC, Prestwick Pharmaceuticals, Inc. is a product-based pharmaceutical company engaged in the development and marketing of small molecule drugs for chronic diseases of the central nervous system (CNS). XENAZINE is the company's lead product development candidate in the U.S. and is currently marketed by the company in Canada under the name NITOMAN(R).

"We are encouraged by the publication of these positive study results, and I am proud to be part of the first pharmaceutical company to submit an NDA in the U.S. for a drug to treat chorea associated with Huntington's Disease," said Kathleen Clarence-Smith, MD, Ph.D., CEO of Prestwick Pharmaceuticals.

"Patients suffering from Huntington's Disease are in need of effective, tolerable therapies for treating their chorea," said Frederick J. Marshall, MD, lead investigator, Huntington Study Group, University of Rochester, New York. "We are very encouraged by these study results. Tetrabenazine demonstrated a significant effect in study patients without causing some of the side effects often experienced with other treatment strategies."

Study Design

This first multicenter, prospective double-blind, placebo-controlled study of XENAZINE involved 84 patients with HD at 16 centers across the U.S. The study examined the efficacy, safety and dose tolerability of XENAZINE versus placebo in treating chorea associated with HD. Patients were randomized to receive XENAZINE (n equals 54) or placebo (n equals 30) for 12 weeks. XENAZINE dosage was titrated upward over a period of seven weeks up to a maximum of 100 mg per day, or until the desired antichoreic effect or intolerable adverse effects occurred, whichever came first. To reduce intolerable side effects, the number of tablets was reduced to the patient's previously well-tolerated level or lower if necessary. In most patients this dose adjustment did not cause loss of chorea efficacy.

The primary outcome was the change from baseline in chorea score as measured by the Unified Huntington's Disease Rating Scale (UHDRS), a research tool that provides an assessment of clinical features. Secondary outcomes included the Clinical Global Impression (CGI) score, a clinician-rated 7-point scale used to assess the severity of illness and change in clinical condition over time.

After 12 weeks, the adjusted mean XENAZINE chorea score declined by 5.0 points, while scores for the placebo group declined by 1.5 points (p less than 0.0001). XENAZINE was superior to placebo as assessed by the CGI scale. In the XENAZINE group, 45% of patients were much- to very-much improved on CGI Global Improvement score compared to only 7% in the placebo group (p equals 0.0004).

Of the 84 patients studied, 93% completed the full 13 weeks of therapy. There were five patients who withdrew from the study in the XENAZINE group and five serious adverse events in four subjects. All four were withdrawn from the study. The serious adverse events consisted of suicide, complicated fall, restlessness/suicidal ideation, and breast cancer. By comparison, there was one withdrawal and no serious adverse events in the placebo group. Dose-limiting adverse events among patients treated with XENAZINE included sedation (27%), akathisia (8%), parkinsonism (4%), and depression as a mood rather than a formal diagnosis (4%). The most common adverse event at week twelve was fatigue, reported by seven patients in the XENAZINE group, compared to two patients in the placebo group. The incidence of adverse events was greater during the upward titration period than during the maintenance phase. At optimal dosage (maintenance phase), there were no significant differences between XENAZINE and placebo with regard to specific adverse events not reported at baseline.

About Huntington's Disease

Huntington's Disease (HD) is an inherited, degenerative brain disorder. The progressive illness affects a person's ability to think, walk, talk and reason. HD is genetic, meaning that it may be passed down from one generation to the next. Children of an HD-afflicted parent have a 50% chance of inheriting the HD gene. Children who inherit the HD gene will eventually develop the illness.

It is estimated that approximately 30,000 people in the U.S. have HD. Another 150,000 people are considered at-risk for the disease because they have or had a first-generation relative with HD. Generally found among adult men and women of all ethnic and racial groups, most people afflicted with HD develop the illness between the ages of 30 and 45. Treatments for HD are aimed at either alleviating the symptoms of the disease or slowing down the underlying progression of the illness. There is no cure for HD.

About Chorea

Chorea can be a debilitating feature of a number of neurological diseases, most notably HD. The condition is characterized by excessive, involuntary and repetitive movements, which may involve the face, limbs or the entire body. In HD, it is the result of over-activity of the neurotransmitter dopamine. Chorea may at first be limited to the fingers and toes. However, as the disease advances, it becomes more widespread. Movements blend or flow into one another, causing them to appear relatively slow and writhing in nature.

About the Huntington Study Group

This clinical study for tetrabenazine, called "TETRA-HD", was organized and conducted by the Huntington Study Group (HSG), a non-profit, cooperative group of Huntington's Disease experts from medical centers in North America, Europe and Australia who are dedicated to improving treatment for persons affected by Huntington's Disease. For more information, visit their web sites at www.Huntington-Study-Group.org and www.HuntingtonProject.org.

About XENAZINE(TM)

XENAZINE has been licensed to Prestwick Pharmaceuticals, Inc. for marketing in the U.S. and Canada by Cambridge Laboratories, Limited, (Cambridge), which has worldwide rights to the product. Cambridge markets the product itself in the UK and Eire (Ireland), and through marketing partners in European and other global markets. XENAZINE is available in some European markets and New Zealand under the same brand name and in Canada and other European markets as NITOMAN(R) for the treatment of hyperkinetic movement disorders. The FDA granted XENAZINE an orphan drug designation for Huntington's Disease, which affects less than 200,000 patients in the U.S. It also designated XENAZINE a fast track product to expedite its review as a new drug that is intended to treat a serious or life-threatening condition.

About Prestwick

Prestwick Pharmaceuticals, Inc. is a product-based specialty pharmaceutical company engaged in the development and marketing of small molecule drugs for chronic diseases of the central nervous system (CNS). Based in Washington, DC, the company was formed in November 2002, and is privately held.

Prestwick Pharmaceuticals has rights to a portfolio of five product candidates obtained under licenses from third parties that address significant unmet needs in the CNS area, including Huntington's Disease, Parkinson's disease, schizophrenia, autism, Alzheimer's disease, and sleep apnea. The company's leading product, tetrabenazine, was licensed from Cambridge Laboratories, Limited, for marketing in the U.S. and Canada. Tetrabenazine is currently being marketed by Prestwick Pharmaceuticals under the brand name NITOMAN(R) in Canada, where the product is indicated for the treatment of hyperkinetic movement disorders.