HONOLULU – October 29, 2009 — Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical company, announced new study results on INTUNIV? (guanfacine) Extended Release Tablets, at a major psychiatric medical meeting today. The primary objective of this study was to assess the change from baseline on the oppositional subscale of the Conners’ Parent Rating Scale-Revised: Long Form (CPRS-R:L) in patients ages 6 to 12 with a primary diagnosis of Attention-Deficit/Hyperactivity Disorder (ADHD) with the presence of oppositional symptoms at baseline. INTUNIV met the primary objective demonstrating significant efficacy in reducing symptoms as measured by the oppositional subscale. Some of the symptoms measured by this scale include deliberately doing things that annoy others, refusing to comply with adults’ requests, and being touchy or easily annoyed by others.
According to the Centers for Disease Control and Prevention (CDC), approximately 7.8 percent of all US school-aged children have been diagnosed with ADHD at some point in their lives. ADHD is a complex neurobehavioral disorder, which includes symptoms and behaviors such as inattentiveness, running around or climbing excessively, and being excitable or impulsive, many of which can be disruptive.
“The disruptive nature of ADHD can impact social and academic settings for those patients diagnosed with the disorder,” said F. Randy Sallee, MD, PhD, Professor of Psychiatry at the University of Cincinnati and Cincinnati Children’s Hospital Medical Center in Cincinnati, Ohio. “This study showed that INTUNIV is an effective option for treating a range of ADHD symptoms.”
INTUNIV, a once-daily formulation of guanfacine, was approved by the US Food and Drug Administration (FDA) on September 2, 2009 as the first selective alpha-2A agonist for the treatment of ADHD. Although the mechanism of action is not known, guanfacine, the active ingredient in INTUNIV, is thought to selectively stimulate alpha-2A adrenoreceptors in the prefrontal cortex. Stimulation of the postsynaptic alpha-2A receptors is thought to strengthen working memory, reduce susceptibility to distraction, improve attention regulation, improve behavioral inhibition, and enhance impulse control.
Once-daily INTUNIV is expected to be available in US pharmacies in November and will come in four dosage strengths (1 mg, 2 mg, 3 mg, and 4 mg). INTUNIV is not a controlled substance and has no known potential for abuse or dependence.
INTUNIV Demonstrated Significant Symptom Reduction in Patients Diagnosed with ADHD and the Presence of Oppositional Symptoms
This randomized, placebo-controlled, flexible-dose study was conducted in 214 patients ages 6 to 12 over a nine-week period. INTUNIV demonstrated significant ADHD symptom improvement in the primary and secondary measures as demonstrated on the Oppositional Subscale of the CPRS-R:L and the ADHD Rating Scale-IV (ADHD-RS-IV), respectively. The CPRS-R:L is a comprehensive scale that uses parent observer and self-report ratings to help assess ADHD symptoms and behaviors in children. At the study’s end, patients taking INTUNIV showed significant symptom reduction as compared to patients taking placebo (-10.9 versus -6.8; effect size 0.59; P<.001) when assessed using the oppositional subscale of the CPRS-R:L. The ADHD-RS-IV scale assesses hyperactive, impulsive, and inattentive ADHD symptoms. ADHD-RS-IV mean change from baseline for INTUNIV versus placebo was -23.8 versus -11.5; effect size 0.92; P<.001. In this study, most treatment-emergent adverse events were mild to moderate. The most commonly reported treatment-emergent adverse events in patients taking INTUNIV (greater than or equal to 10 percent) were somnolence, headache, sedation, upper abdominal pain, and fatigue.
Dr Sallee added, “The data presented today provide additional support for the safety and efficacy profile of INTUNIV. The trial’s flexible dose design gives clinicians a better look at how this medication may be used in clinical practice once it becomes available in November.”
Additional information about INTUNIV and Full Prescribing Information are available at http://www.intuniv.com.
Important Safety Information
INTUNIV is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children and adolescents aged 6 to 17. Efficacy was established in two controlled clinical trials (8 and 9 weeks in duration). The physician electing to use INTUNIV for extended periods should periodically reevaluate its long-term usefulness for the individual patient.
INTUNIV should not be used in patients with a history of hypersensitivity to guanfacine or any of its inactive ingredients or by patients taking other products containing guanfacine.
Hypotension, bradycardia, and syncope were observed in clinical trials. Use INTUNIV with caution in treating patients who have experienced hypotension, bradycardia, heart block, or syncope, or who may have a condition that predisposes them to syncope; are treated concomitantly with antihypertensives or other drugs that can reduce blood pressure or heart rate or increase the risk of syncope. Heart rate and blood pressure should be measured prior to initiation of therapy, following dose increases, and periodically while on therapy. Patients should be advised to avoid becoming dehydrated or overheated.
Sedation and somnolence were commonly observed in clinical trials. The potential for additive sedative effects with CNS depressant drugs should be considered. Patients should be cautioned against operating heavy equipment or driving until they know how they respond to INTUNIV. Avoid use with alcohol.
Common adverse reactions in patients taking INTUNIV that may be dose related over the range of 1 to 4 mg/day include somnolence, sedation, abdominal pain, dizziness, hypotension/decreased blood pressure, dry mouth, and constipation.
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 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 disorder. 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/or medication.
For further information please contact:
Matthew Cabrey (North America)
+1 484 595 8248
Debra Gemme (Porter Novelli for Shire)
+1 703 298 4030
Alana Brier (Porter Novelli for Shire)
+1 212 601 8432
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 Web site: 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, 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.