WASHINGTON, May 7 -- Shire plc(LSE: SHP, Nasdaq: SHPGY), the global specialty biopharmaceutical company, presented today at a major scientific meeting findings from analyses of pivotal trial results of INTUNIV, a selective alpha-2A-agonist. This compound is an investigational once-daily medication, which is being evaluated for the treatment of the symptoms of Attention Deficit Hyperactivity Disorder (ADHD). The data demonstrated that INTUNIV showed significant efficacy in reducing ADHD symptoms for patients taking the medication when compared to patients taking placebo at all measured time points up to 24 hours postdose.
The U.S. Food and Drug Administration (FDA) issued an approvable letter on June 20, 2007, regarding INTUNIV. Shire is conducting additional clinical work which is designed to enhance the label. Upon approval, INTUNIV will be the first selective alpha-2A receptor agonist indicated for the treatment of ADHD that may provide an important treatment option for patients and physicians.
Summary of Analyses
The pooled analysis evaluated results from these patients on a weight adjusted mg/kg basis from two similarly designed, randomized, double-blind, forced-dose titration, multicenter phase III trials. The primary efficacy measure for both studies was change in the ADHD Rating Scale (ADHD-RS-IV) total score from baseline to endpoint. All patient groups treated with INTUNIV showed significantly greater improvement in ADHD-RS-IV total score from baseline to endpoint than the placebo group (P < .001). The ADHD-RS-IV is a standardized, validated test for assessing symptoms of ADHD and for assessing their response to treatment.
The analysis also studied duration of effect using the Conners' Parent Rating Scale-Revised Short Form (CPRS-R), which is a comprehensive scale that used observer and self-report ratings to help assess ADHD and evaluate behavioral issues in children and adolescents. The CPRS-R assessments were completed on specified days at approximately 6 PM (after school and before dinner), 8 PM (dinner through bedtime) and 6 AM (waking time/new dose administration time), which represented 12, 14 and 24 hours after the administration of the dose of INTUNIV, respectively. The data demonstrated significant improvement of ADHD symptoms based on total endpoint CPRS-R scores for all weight adjusted dose groups treated with INTUNIV when compared to placebo for all time periods (at 12 hours, P < = .001; at 14 hours, P < .001; and at 24 hours, P=.003).
A separate analysis of the same phase III studies evaluated the percentage of ADHD patients who responded to weight-adjusted treatment with INTUNIV versus those participants receiving placebo. Using the change in the ADHD-RS-IV total score from baseline to endpoint as the primary efficacy measure, responders were defined as those with a 25 percent reduction in score from baseline to endpoint. Findings from the analysis showed that all groups treated with INTUNIV responded to the medication in a shorter time period than the placebo group (14 days versus 20 days, respectively, P = .001).
In the phase III studies, adverse events (AEs) were reported in 80.7 percent of patients treated with INTUNIV and 71.8 percent of patients treated with placebo. Overall, the AEs were mostly mild to moderate in severity. Adverse reactions that appeared to be dose-related in patients given INTUNIV included upper abdominal pain, constipation, dizziness, dry mouth, hypotension, sedation, and somnolence. Serious AEs reported in these analyses were uncommon and rates were similar between patients treated with INTUNIV and patients treated with placebo (0.6% of the INTUNIV group and 0.7% of placebo group, respectively).
INTUNIV, a once-daily formulation of guanfacine, provides a controlled, steady delivery of drug throughout the day with a delivery system that is designed to minimize the fluctuations between peak and trough concentrations as seen with immediate-release guanfacine. INTUNIV is not a controlled substance and does not appear to have a known mechanism for potential abuse or dependence.
Although other ADHD medications work indirectly in the prefrontal cortex, it has been shown that guanfacine, the active ingredient in INTUNIV, works directly by binding selectively to alpha-2A adrenergic cell receptors located in the prefrontal cortex. The prefrontal cortex is an area of the brain associated with executive functioning, ie, working memory, behavioral inhibition, regulation of attention, distractibility, impulsivity, and frustration tolerance. The selective alpha-2A agonist strengthens working memory and prefrontal cortex neuronal firing. This research supports the use of guanfacine for the treatment of ADHD.
Safety data showed that adverse events reported by participants using INTUNIV were generally mild to moderate in severity, with the most common side effects being sedative in nature. Sedation-related, treatment-emergent adverse events were among the most common but emerged in the first two weeks and were usually transient and mild or moderate in severity. Treatment-related adverse events greater than 10 percent included somnolence (32 percent), headache (26 percent), fatigue (18 percent), upper abdominal pain (14 percent) and sedation (13 percent). Small to modest changes in blood pressure, pulse rate, and ECG parameters were observed.
ADHD is one of the most common psychiatric disorders in children and adolescents. Approximately 7.8 percent of all school-aged children, or about 4.4 million U.S. children aged 4 to 17 years, have been diagnosed with ADHD at some point in their lives, according to the U.S. Centers for Disease Control and Prevention (CDC). The disorder is also estimated to affect 4.4 percent of U.S. adults aged 18-44 based on results from the National Comorbidity Survey Replication, a nationally representative household survey, which used a lay-administered diagnostic interview to assess a wide range of DSM-IV disorders. ADHD is a neurobiological 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 level of development. To be properly diagnosed with ADHD, a child needs to demonstrate at least six of nine symptoms of inattention; and/or at least six of nine symptoms of hyperactivity/impulsivity; the onset of which appears before age 7 years; that some impairment from the symptoms is present in two or more settings (e.g., at school and home); that the symptoms continue for at least six months; and that there is clinically significant impairment in social, academic or occupational functioning and the symptoms cannot be better explained by another psychiatric disorder.
Although there is no "cure" for ADHD, there are accepted treatments that specifically target its symptoms. The most common standard treatments include educational approaches, psychological or behavioral modification, and medication.
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Porter Novelli for Shire
Shire's strategic goal is to become the leading specialty biopharmaceutical company that focuses on meeting the needs of the specialist physician. Shire focuses its business on attention deficit and hyperactivity disorder (ADHD), human genetic therapies (HGT), gastrointestinal (GI) and renal diseases. The structure is sufficiently flexible to allow Shire to target new therapeutic areas to the extent opportunities arise through acquisitions. Shire's in-licensing, merger and acquisition efforts are focused on products in niche markets with strong intellectual property protection either in the US or Europe. Shire believes that a carefully selected portfolio of products with strategically aligned and relatively small-scale sales forces will deliver strong results.
For further information on Shire, please visit the Company's website: 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 including, but not limited to the successful development of JUVISTA(R) (Human TGF(beta)3) and velaglucerase alfa (GA-GCB); manufacturing and commercialization including, but not limited to, the establishment in the market of VYVANSE(TM) (lisdexamfetamine dimesylate) (Attention Deficit and Hyperactivity Disorder ("ADHD")); the impact of competitive products, including, but not limited to, the impact of those on Shire's 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 date of INTUNIV(TM) (guanfacine extended release) (ADHD); Shire's ability to secure new products for commercialization and/or development; and other risks and uncertainties detailed from time to time in Shire plc's filings with the Securities and Exchange Commission, including Shire plc's Annual Report on Form 10-K for the year ended December 31, 2007.