Investigational Nonstimulant Guanfacine XR Significantly Improved Child, Adolescent ADHD Symptoms

Shire plc (LSE: SHP, NASDAQ: SHPGY, TSX: SHQ) has announced the positive results of studies of the investigational medication guanfacine extended release (GXR, previously referred to as SPD503), a selective alpha-2A-adrenoceptor agonist. These data from two short-term phase III placebo-controlled studies and two long-term phase III open-label studies, presented at the 2007 American Psychiatric Association (APA) annual meeting, demonstrated that GXR significantly improved all core symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) in children aged 6 to 17 years.



"Guanfacine extended release, the first selective alpha-2A-adrenoceptor agonist to be tested in well-controlled studies as a treatment for ADHD, holds potential based on the significant improvements in ADHD symptoms documented in four studies of this investigational drug," stated co-author Joseph Biederman, M.D., lead investigator, chief of clinical and research program in pediatric psychopharmacology at Massachusetts General Hospital and professor of psychiatry at Harvard Medical School. "Moreover, these data presented at this medical conference add evidence that GXR when dosed once daily may continue to control children's ADHD symptoms for up to 24 months."



GXR, a nonstimulant, is not a controlled substance and does not appear to have a mechanism for potential abuse or dependence. Shire submitted a New Drug Application (NDA) for GXR on August 24, 2006, which is currently under FDA review. The NDA provided data on GXR 1 mg to 4 mg taken once daily for the treatment of children and adolescents with ADHD.



GXR Yielded Significant Reductions in ADHD-RS-IV Scores in Two Short-Term Trials



Results from two short-term, double-blind, randomized phase III clinical trials presented at this medical conference, demonstrated that GXR significantly controlled all core symptoms of ADHD, including inattention, hyperactivity and impulsivity in children aged 6 to 17 years previously diagnosed with ADHD, as measured by several standardized tests when compared to placebo treatment.



In the two short-term trials, the primary endpoint was a reduction in ADHD symptoms as measured by the ADHD Rating Scale (ADHD-RS-IV). ADHD-RS-IV is a standardized, validated test for assessing symptoms of ADHD in children and for assessing their response to treatment. This scale, which contains 18 items, is based on the ADHD diagnostic criteria as defined in the APA's Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision.



In the first trial, 301, investigators compared 2 mg, 3 mg or 4 mg GXR doses to placebo during an eight-week treatment period. The participants randomized to GXR all began at the 1 mg dose. At weekly visits, doses were titrated in 1 mg increments over the first four weeks to achieve the randomized dose. Then, doses were tapered down weekly so that all participants randomized to GXR received the 1 mg dose at week eight.
















Participants achieved overall significant mean reductions from baseline in ADHD-RS-IV total scores by study end, -16.7 points vs. -8.9 for placebo (P