San Francisco, CA – May 18, 2009 – Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical company, today announced new findings on INTUNIV (guanfacine) extended release, a selective alpha-2A-agonist, at a major psychiatric meeting. This randomized placebo controlled trial met its primary objective, which was to evaluate the effects of INTUNIV on oppositional symptoms in children aged 6 to 12 years with a diagnosis of ADHD and the presence of oppositional symptoms. The data presented today on this investigational compound reviewed secondary efficacy measures from three different rating scales.
"A significant number of pediatric ADHD patients present with behaviors such as anger, resentfulness, defiance, and arguing with adults. It can be complicated for physicians and caregivers to find the right medication to control symptoms for children with ADHD exhibiting these behaviors," said Daniel Connor, MD, professor and division chief of child and adolescent psychiatry at the University of Connecticut Medical School. "When considered with the primary efficacy results of the current study, these data provide additional support for the clinical efficacy of INTUNIV for treating ADHD in this patient population."
On January 26, 2009, Shire filed a resubmission to the US Food and Drug Administration (FDA) of the New Drug Application to support approval for the treatment of ADHD in children and adolescents. Once available, INTUNIV will be the first selective alpha-2A receptor agonist approved for the treatment of ADHD.
INTUNIV Demonstrated Significant Efficacy in Secondary Endpoints
In this randomized, placebo-controlled, flexible-dose study, INTUNIV demonstrated significant ADHD symptom improvement in patients with oppositional symptoms as measured by the ADHD Rating Scale-IV (ADHD-RS-IV), a scale frequently used in ADHD clinical trials. In results from this study presented today, INTUNIV also demonstrated symptom improvement as measured by three different rating scales: the Clinical Global Impressions-Improvement (CGI-I), the Conduct Problem Subscale of the New York Parent Rating Scale-School-Aged (NYPRS-S), and the Parent Stress Index-Short Form (PSI/SF) questionnaire.
When using the CGI-I scale, investigators rated 7 out of 10 patients as "very much improved" or "much improved" compared with placebo (71.5 percent vs 32.0 percent; P< .001). The CGI-I scale is a standard assessment used to rate the severity of a patient's illness and improvement over the course of the study.
Significantly greater symptom reductions were also seen on the Conduct Problem Subscale of the NYPRS-S in the INTUNIV group compared to placebo (-16.0 vs -9.6; P< .001). In this parent-rated scale, numerous symptoms including anger, defiance, arguing with adults, and loss of temper were assessed in children on a four-point scale and a higher score indicated greater problems. Additional improvement was demonstrated on the PSI/SF, a parent rated 36-item questionnaire that measured stressful areas in parent-child interactions. On the PSI/SF scale, the INTUNIV group reduced its score by 17.0 compared to 7.7 for the placebo group (P=.002).
"These data are testament to Shire's commitment to furthering ADHD research, and finding new treatment options for the multiple symptoms of ADHD, many of which are very disruptive at home and at school," said Michael Yasick, Senior Vice President of Shire's ADHD Business Unit.
In this study, the most commonly reported treatment emergent adverse events (greater than or equal to 10 percent) were somnolence, headache, sedation, upper abdominal pain, fatigue and irritability. The majority of treatment emergent adverse events were mild to moderate in severity. There were no serious adverse events.
About INTUNIV
INTUNIV is currently being studied as a once-daily, extended release formulation of guanfacine designed to provide steady delivery of drug throughout the day. INTUNIV is pending FDA approval for the treatment of ADHD in children and adolescents. In clinical trials, INTUNIV demonstrated significant reduction in ADHD symptoms. INTUNIV is not a controlled substance and has no known mechanism for abuse or dependence.
Guanfacine, the active ingredient in INTUNIV, is thought to work directly by binding selectively to alpha-2A adrenergic receptors located in the prefrontal cortex. The prefrontal cortex is an area of the brain associated with working memory, behavioral inhibition, regulation of attention, distractibility, and impulsivity. Although the mechanism of action of guanfacine in the treatment of ADHD is not fully understood, preclinical research suggests this selective alpha-2A agonist strengthens working memory and prefrontal cortex neuronal firing. This research supports the use of guanfacine for the treatment of ADHD.
In pivotal clinical trials, 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 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). Syncope occurred in approximately 1 percent of pediatric patients in the clinical program. The majority of these cases occurred in the long-term, open label studies. Small to modest changes in blood pressure, pulse rate, and ECG parameters were observed.
About ADHD
ADHD is one of the most common psychiatric disorders in children and adolescents. Worldwide prevalence of ADHD is estimated at 5.3 percent (with large variability), according to a comprehensive systematic review of this topic published in 2007 in the American Journal of Psychiatry. In the United States, approximately 7.8 percent of all school-aged children, or about 4.4 million US children aged 4 to 17 years, have been diagnosed with ADHD at some point in their lives, according to the Centers for Disease Control and Prevention (CDC).
ADHD is a psychiatric behavioral 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. The specific etiology of ADHD is unknown and there is no single diagnostic test for this syndrome. Adequate
diagnosis requires the use of medical and special psychological, educational and social resources, utilizing diagnostic criteria such as Diagnostic and Statistical Manual of Mental Disorders™-IV (DSM-IV) or International Classification of Diseases 10 (ICD-10).
Although there is no "cure" for ADHD, there are accepted treatments that specifically target its symptoms. Standard treatments include educational approaches, psychological, or behavioral modification, and medication.
For further information please contact:
Porter Novelli for Shire
Debra Gemme
212.601.8342
703.298.4030 (mobile)
debra.gemme@porternovelli.com
Alana Brier
212.601.8432
203.565.3980 (mobile)
alana.brier@porternovelli.com
SHIRE PLC
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 hyperactivity disorder (ADHD), human genetic therapies (HGT) and gastrointestinal (GI) diseases as well as opportunities in other therapeutic areas to the extent they arise through acquisitions. Shire's in-licensing, merger and acquisition efforts are focused on products in specialist markets with strong intellectual property protection and global rights. Shire believes that a carefully selected and balanced 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.
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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, the Company's results could be materially adversely affected. The risks and uncertainties include, but are not limited to, risks associated with: the inherent uncertainty of research, development, approval, reimbursement, manufacturing and commercialization of the Company's Specialty Pharmaceutical and Human Genetic Therapies products, as well as the ability to secure and integrate new products for commercialization and/or development; government regulation of the Company's products; the Company's ability to manufacture its products in sufficient quantities to meet demand; the impact of competitive therapies on the Company's products; the Company's ability to register, maintain and enforce patents and other intellectual property rights relating to its products; the Company's ability to obtain and maintain government and other third-party reimbursement for its products; and other risks and uncertainties detailed from time to time in the Company's filings with the Securities and Exchange Commission.