SAN DIEGO - MAY 23, 2007 - Shire plc (LSE: SHP, NASDAQ: SHPGY, TSX: SHQ) announced today that DAYTRANA™ (methylphenidate transdermal system), its Attention Deficit Hyperactivity Disorder (ADHD) patch, had significant efficacy in reducing the symptoms of ADHD in both male and female children aged 6 to 12 years, according to clinical trial results reported at the American Psychiatric Association (APA) annual meeting in San Diego.
"Few clinical studies have examined gender differences in the response to ADHD treatments. Our study documented that DAYTRANA offered a favorable safety profile and was an effective ADHD treatment in both boys and girls," said Robert Findling, M.D., lead investigator and Professor of Psychiatry at Case Western Reserve University and Director of the Division of Adolescent and Child Psychiatry at University Hospitals Case Medical Center. "The study provides a platform to open a dialogue about gender and ADHD."
Approximately 4.4 million U.S. children aged 4 to 17 years -- about 7.8 percent of all school-age children -- have been diagnosed with ADHD at some point in their lives, according to the U.S. Centers for Disease Control and Prevention (CDC). Studies estimated that 11.0 percent of boys have been diagnosed with ADHD in contrast to only 4.4 percent of girls. Experts believe that girls with ADHD are underdiagnosed and, therefore, undertreated.
Shire's DAYTRANA is the first and only patch medication approved by the U.S. Food and Drug Administration (FDA) to treat the symptoms of ADHD in children aged 6 to 12 years. DAYTRANA is available in four dosage strengths - 10 mg, 15 mg, 20 mg and 30 mg - all designed for once-daily use. When worn for the recommended nine hours, efficacy has been demonstrated from the first time point measured (two hours) through the 12-hour time point. Because Daytrana is a patch, physicians may recommend that patients shorten the wear time if shorter duration of effect is desired or to help manage the potential for late-day side effects.
Significant Symptom Control for Boys and Girls In this double-blind, 7-week, parallel-group study, investigators randomized 270 children to receive DAYTRANA, OROS methylphenidate or placebo. The 96 children (ITT population) in the DAYTRANA group reported a significant mean reduction of 56.5 percent in their ADHD Rating Scale-IV (ADHD-RS-IV) total scores (-24.24±14.55 points, P<.0001 vs. placebo) from the study start to end, the study's primary endpoint.
The 58 boys that received DAYTRANA averaged a significant 56 percent ADHD-RS-IV total score reduction (-24.28±15.66 points, P<.0001), while the 38 girls averaged a significant 57.4 percent reduction (-24.18±12.88 points, P<.0001).
ADHD-RS-IV assesses 18 individual symptoms of ADHD as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR®), a publication of the American Psychiatric Association.
Investigators monitored adverse events throughout the study and for 30 days after the last dose. Adverse events typically were mild to moderate in severity and were consistent with known effects of methylphenidate. No serious adverse events were reported.
The most common treatment-emergent adverse events (>10 percent) in both boys and girls in the trial were decreased appetite, headache, insomnia, nausea and vomiting. Boys in the DAYTRANA group had a higher incidence of vomiting (9 boys vs. 1 girl), tic (7 vs. 0), upper abdominal pain (6 vs. 1), irritability (7 vs. 0) and affect lability (6 vs. 0).
The study was supported by funding from Shire.
Approximately 7.8 percent of all school-age 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 CDC. ADHD is one of the most common psychiatric disorders in children and adolescents. ADHD is a neurobiological psychiatric 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.
Shire ADHD Portfolio
Shire's portfolio of ADHD treatments includes VYVANSE™ (lisdexamfetamine dimesylate), the first prodrug stimulant, which is planned to launch June 2007, DAYTRANA™ (methylphenidate transdermal system), the first and only ADHD patch, and ADDERALL XR® (mixed salts of a single-entity amphetamine product), a long-acting formulated stimulant. Additional ADHD treatments under development by Shire include SPD465 (triple-bead mixed amphetamine salts) and SPD503 (guanfacine HCl extended release).
For further information please contact:
Porter Novelli for Shire
Marion E. Glick
917.301.4206 (on site at APA)
203.470.0836 (on site at APA)
May 23, 2007; 12:00 p.m. PDT (3:00 p.m. EDT)
Sails Pavilion, Upper Level, San Diego Convention Center
Efficacy and Safety of MTS in Male and Female Pediatric Subjects with ADHD Robert L. Findling, M.D.; Samuel Boellner, M.D.; John C. Burnside, M.D.; Oscar G. Bukstein, M.D.; MaryAnn Livolsi, M.S.N., R.N.
Important Safety Information
Tell your doctor about any heart conditions, including structural abnormalities, your child or a family member may have. Inform your doctor immediately if the child develops symptoms that suggest heart problems, such as chest pain or fainting.
Daytrana should not be used if the child has: significant anxiety, tension, or agitation; allergies to methylphenidate or other ingredients of Daytrana; glaucoma; discontinued in the last 14 days or is taking a monoamine oxidase inhibitor (MAOI); tics, or family history or diagnosis of Tourette's syndrome.
Tell your doctor before using Daytrana if the child: is being treated for or has symptoms of depression (e.g. sadness, worthlessness, or hopelessness) or bipolar disorder; has family history of tics; has abnormal thoughts or visions, hears abnormal sounds, or has been diagnosed with psychosis; has had seizures or abnormal EEGs; has or has had high blood pressure; exhibits aggressive behavior or hostility. Tell your doctor immediately if the child develops any of these conditions/symptoms while using Daytrana.
In clinical studies, side effects were generally mild to moderate. The most common side effects reported with Daytrana were decreased appetite, sleeplessness, sadness/crying, twitching, weight loss, nausea, vomiting, tics, and affect lability (mood swings). Aggression, new abnormal thoughts/behaviors, mania, and growth suppression have been associated with use of drugs of this type. Tell your doctor if the child has blurred vision while using Daytrana.
Abuse of Daytrana can lead to dependence.
Daytrana should be applied daily to clean, dry skin, which is free of any cuts or irritation. Skin irritation or allergic skin rash may occur.
For Full Prescribing Information go to www.DAYTRANA.com.
About VYVANSE and ADDERALL XR
VYVANSE or ADDERALL XR should not be taken by patients who have advanced arteriosclerosis; symptomatic cardiovascular disease; moderate to severe hypertension; hyperthyroidism; known hypersensitivity or idiosyncrasy to sympathomimetic amines; agitated states; glaucoma; a history of drug abuse; or during or within 14 days after treatment with monoamine oxidase inhibitors (MAOIs).
Sudden death has been reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems. Sudden deaths, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses in ADHD. Physicians should take a careful patient history, including family history, and physical exam, to assess the presence of cardiac disease. Patients who report symptoms of cardiac disease such as exertional chest pain and unexplained syncope should be promptly evaluated. Use with caution in patients whose underlying medical condition might be affected by increases in blood pressure or heart rate.
New psychosis, mania, aggression, growth suppression, and visual disturbances have been associated with the use of stimulants. Use with caution in patients with a history of psychosis, seizures or EEG abnormalities, bipolar disorder, or depression. Growth monitoring is advised during prolonged treatment.
Amphetamines have a high potential for abuse. Administration of amphetamines for prolonged periods of time may lead to drug dependence. Particular attention should be paid to the possibility of subjects obtaining amphetamines for non-therapeutic uses or distribution to others and the drugs should be prescribed or dispensed sparingly. Misuse of amphetamine may cause sudden death and serious cardiovascular adverse events.
The most common adverse events reported in clinical studies of VYVANSE included: pediatric - loss of appetite, insomnia, abdominal pain, and irritability. The most common adverse events reported in clinical studies of ADDERALL XR included: pediatric - loss of appetite, insomnia, abdominal pain, and emotional lability; adolescent - loss of appetite, insomnia, abdominal pain, and weight loss; adult - dry mouth, loss of appetite, insomnia, headache, and weight loss.
About SPD465 (triple-bead mixed amphetamine salts):
SPD465 recently received an approvable letter from U.S. Food and Drug Administration (FDA) for the treatment of ADHD in adults. SPD465, a single entity, mixed amphetamine salt formulation was studied to determine if it provides symptom control for up to 16 hours in adults with ADHD. The most commonly reported treatment-emergent adverse events were decreased appetite, insomnia, dry mouth, headache, upper abdominal pain and anorexia.
About SPD503 (guanfacine HCl extended release):
SPD503 is currently under review with FDA for the treatment of ADHD in children aged 6 to 17 years. SPD503 is a once-daily formulation of the selective alpha-2A-adrenoceptor agonist guanfacine and was studied to determine if it provided control of ADHD symptoms throughout the day in children aged 6 to 17 years. The most commonly reported treatment-emergent adverse events were headache, somnolence, fatigue, upper abdominal pain and sedation.
Notes to editors
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 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 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. 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.
For further information on Shire, please visit the Company's website: www.shire.com
THE "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 SPD503 (guanfacine extended release) (ADHD) and SPD465 (extended release triple-bead mixed amphetamine salts) (ADHD); Shire's ability to secure new products for commercialization and/or development; Shire's ability to benefit from its acquisition of New River Pharmaceuticals Inc.; and other risks and uncertainties detailed from time to time in Shire plc's filings with the Securities and Exchange Commission, particularly Shire plc's Annual Report on Form 10-K for the year ended December 31, 2006.
Daytrana™ is a trademark of Shire Pharmaceuticals Ireland Limited.