Positive study results for methylphenidate transdermal system

Main Category: ADHD
Article Date: 14 Nov 2005 - 8:00 PDT

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Shire announced at the US Psychiatric and Mental Health Congress in Las Vegas, Nevada, that its investigational methylphenidate transdermal system (MTS) demonstrated statistically significant reductions in the symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) and was generally well tolerated in patients aged 6 to 12 in two clinical trials.

"Children who have ADHD must cope with symptoms throughout the day and in a number of environments, including in the classroom, during extra-curricular activities, or while at home," explained Frank Lopez, MD, developmental pediatrician at the Children's Developmental Center, Maitland, Florida. "While oral methylphenidate has long been a first-line treatment for patients with ADHD symptoms, if approved, this transdermal patch formulation would provide parents and health care professionals the first and only non-oral medication for children with ADHD."

The MTS patch was developed by Noven Pharmaceuticals, Inc. and combines the active ingredient of methylphenidate with transdermal technology. This transdermal deliveryäNoven's patented DOT Matrix system was designed to provide continuous medication release throughout the day. The transdermal system releases medication that passes through the skin and directly into the blood stream. The patch is water-resistant.

Data from phase II and phase III clinical trials presented this week in Las Vegas demonstrated statistically significant improvements in the primary and secondary endpoints analyzed for children treated with MTS compared to children treated with placebo.

The phase II analog classroom study included 79 children with ADHD. The patch was worn for nine hours, and efficacy was assessed throughout the day for twelve hours. MTS demonstrated statistically significant improvement over placebo on the measures tested. Behavior, which was measured using the Swanson, Kotkin, Agler, M-Flynn, and Pelham -Deportment (SKAMP-D) scale, was improved with MTS overall (mean score 3.2 for MTS versus 8.0 for placebo) and at all time points throughout the day (P < 0.001).

Children taking MTS also completed more math problems correctly on the Permanent Product Measure of Performance (PERMP) scale than did those taking placebo (110 versus 81, respectively).

In the phase III naturalistic trial with 270 participants, investigators found that MTS worn for nine hours reduced the children's overall symptoms of ADHD, compared to a placebo (P < 0.0001), as measured by scores on the ADHD Rating Scale (ADHD-RS). By the study's end, mean ADHD-RS scores declined -24.2 points (56%) from baseline for children treated with MTS versus a decline of -9.9 (24%) for those treated with placebo (P < 0.0001). ADHD-RS assesses 18 individual symptoms of ADHD as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision(TM), a publication of the American Psychiatric Association.

In both studies, MTS was generally well tolerated during both the dose optimization and double-blind phases. Adverse events typically were mild to moderate, resolved with continued therapy and were consistent with known effects of methylphenidate. The most common adverse events reported by patients who received MTS in clinical trials were: nausea, vomiting, nasopharyngitis, weight decreased, anorexia, decreased appetite, affect lability, insomnia, tic, and nasal congestion.

Shire and Noven provided funds for both studies.

Noven and Shire are seeking approval for MTS and the application is currently under review by the FDA. The trade name DAYTRANA(TM) has been proposed to the FDA and is currently under review.

About MTS

MTS is not intended to be administered to patients with: marked anxiety, tension or agitation; allergies to methylphenidate or other ingredients in MTS; skin sensitivities to soaps, lotions, cosmetics or adhesives; eczema, psoriasis, dermatitis or sensitive skin syndrome. MTS has not been studied in children under 6 years of age. Patients will be advised to avoid direct external heat to the patch application site. MTS will need to be stored in a safe place, out of the reach of children.

Methylphenidate should not be administered to patients with:
glaucoma; tics, Tourette's syndrome or a family history of Tourette's syndrome; current or recent use of Monoamine Oxidase Inhibitors (MAOIs). Chronic abuse of methylphenidate may lead to dependence and careful supervision following withdrawal from abuse is warranted. Methylphenidate should not be given to patients with a history of drug dependence or alcoholism. Methylphenidate should not be used for the prevention or treatment of severe depression or normal fatigue states. Growth should be monitored in patients treated with methylphenidate. Use with caution in patients with psychosis, history of seizures or EEG abnormalities, hypertension, and history of drug dependence or alcoholism. Rare cases of visual disturbances have been reported with methylphenidate use. Hematologic monitoring is advised during prolonged therapy.

About ADHD

ADHD affects approximately 7.8 percent of all school-age children, more than 4 million in the United States. ADHD is considered the most commonly diagnosed psychiatric disorder in children and adolescents. ADHD is a neurological brain disorder that manifests as a persistent pattern of inattention and/or hyperactivity-impulsivity that is more frequent and severe than is typically observed in individuals at a comparable age and maturity. If untreated, ADHD can acutely affect a child's life, leading to problems with family members, friends, sports, after-school activities and academics.

Shire Pharmaceuticals Group plc

Shire's strategic goal is to become the leading specialty pharmaceutical company that focuses on meeting the needs of the specialist physician. Shire focuses its business on central nervous system (CNS), gastrointestinal (GI), general products (GP) and human genetic therapies (HGT) - all being areas in which Shire has a commercial presence. The structure is sufficiently flexible to allow Shire to target new therapeutic areas to the extent opportunities arise through acquisitions. Shire believes that a carefully selected portfolio of products with a strategically aligned and relatively small-scale sales force will deliver strong results.

Shire's focused strategy is to develop and market products for specialty physicians. This approach aims to deliver increased returns and lower risks. Shire's in-licensing and merger and acquisition efforts are focused on products in niche markets with strong intellectual property protection either in the US or Europe.

For further information on Shire, please visit the Company's website: http://www.shire.com

"SAFE HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995

Statements included herein that are not historical facts are forward-looking statements. Such forward-looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, Shire's results could be materially affected. The risks and uncertainties include, but are not limited to, risks associated with: the inherent uncertainty of pharmaceutical research, product development, manufacturing and commercialization; the impact of competitive products, including, but not limited to, the impact of those on Shire's Attention Deficit and Hyperactivity Disorder (ADHD) franchise; patents, including, but not limited to, legal challenges relating to Shire's ADHD franchise; government regulation and approval, including, but not limited to, the expected product approval dates of DAYTRANA (MTS/METHYPATCH) (ADHD), SPD503 (ADHD), SPD465 (ADHD), MESAVANCE (SPD476) (ulcerative colitis), I2S (iduronate-2-sulfatase) (Hunter syndrome), and NRP104 (ADHD), including its scheduling classification by the Drug Enforcement Administration in the United States; Shire's ability to benefit from its acquisition of Transkaryotic Therapies, Inc.; Shire's ability to secure new products for commercialization and/or development; and other risks and uncertainties detailed from time to time in Shire's filings with the Securities and Exchange Commission, including its Annual Report on Form 10-K for the year to December 31, 2004.

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Matthew Cabrey
484-595-8248B
Media Relations
Brian Piper
484-595-8252
Investor Relations
Shire Pharmaceuticals Group
http://www.shire.com/shire/index.jsp