SAN DIEGO - May 23, 2007 - Shire plc (LSE: SHP, NASDAQ: SHPGY, TSX: SHQ) today announced that VYVANSE™ (lisdexamfetamine dimesylate) effectively controlled Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms in children aged 6 to 12 years. In addition, 95 percent of children taking VYVANSE daily for 12 months showed overall improvement, according to phase III open-label extension trial results. Further analysis of phase II clinical data demonstrated that VYVANSE provided consistent time to maximum concentration of d-amphetamine from patient to patient. Both studies were presented today at the annual meeting of the American Psychiatric Association (APA).
The U.S. Food and Drug Administration (FDA) approved VYVANSE for the treatment of ADHD on Feb. 23, 2007. VYVANSE remains on track for commercial launch in June 2007.
"Our research concluded that patients taking a daily morning dose of VYVANSE for up to 12 months demonstrated consistent control in ADHD symptoms from month to month," said Robert Findling, M.D., lead investigator of the long-term open-label study 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. "As the first prodrug stimulant, VYVANSE will provide a novel approach to the delivery of stimulant medication for the treatment of ADHD."
Long-term Treatment with VYVANSE Yields Significant ADHD Symptom Improvement
In the long-term open-label extension trial, patients taking VYVANSE showed a greater than 60 percent improvement in the symptoms of ADHD, based on the participants' average change in ADHD Rating Scale (ADHD-RS-IV) scores* from baseline, the primary endpoint, after one year of treatment. Specifically, mean scores decreased 63 percent from baseline (P <.0001). Additionally, 95 percent of patients who received 12 months of daily treatment were rated as "very much improved" or "much improved" by physicians on the Clinical Global Impressions-Improvement (CGI-I) scale, a secondary endpoint.
All 272 patients in the long-term trial previously participated in either of two double-blind clinical trials of VYVANSE. In the long-term trial, investigators provided participants with 30 mg once-daily doses of VYVANSE for one week, and then adjusted the dosage by 20 mg at weekly intervals during three subsequent visits to achieve optimal efficacy and tolerability. Participants continued treatment for the remaining 11 months. The maximum daily dose was 70 mg.
Safety was also evaluated during the study and VYVANSE was generally well tolerated. Most treatment-associated adverse events were mild to moderate in severity, occurred during the first eight weeks of treatment and incidence decreased over time. The most frequently reported adverse events in this trial were decreased appetite, headache, decreased weight and insomnia.
VYVANSE Demonstrated Consistent Time to Maximum Concentration of d-amphetamine from Patient to Patient
A once-daily 70 mg dose of VYVANSE provided low variability in the time from administration to maximum concentration of d-amphetamine from patient to patient. This finding was based on data from 17 children with ADHD aged 6 to 12 years enrolled in a double-blind phase II crossover trial examining the efficacy and safety of VYVANSE and mixed amphetamine salts extended release (MAS XR) in comparison to placebo.
Patients taking VYVANSE achieved maximum d-amphetamine concentration within a narrow time window of 4.5 to 6 hours. Patients taking MAS XR achieved maximum d-amphetamine concentration between 3 to 12 hours.
New River Pharmaceuticals Inc. supported both studies.
Additional information about VYVANSE and Full Prescribing Information are available at www.Vyvanse.com.
*ADHD-RS-IV is a standardized, validated test for assessing symptoms of ADHD in children and for assessing their response to treatment. The scale, which contains 18 items, is based on the ADHD diagnostic criteria as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision®, a publication of the American Psychiatric Association. The CGI-I also is a standard assessment tool and rates the severity of a patient's illness, improvement over time and efficacy of medication.
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 U.S. Centers for Disease Control and Prevention (CDC). ADHD is one of the most common psychiatric disorders in children and adolescents. 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.
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)
917.392.0756 (on site at APA)
APA # NR739
Long-term Effectiveness and Safety of Lisdexamfetamine Dimesylate (LDX) in Children Aged 6 to 12 Years With Attention-Deficit/Hyperactivity Disorder
May 23, 2007; 3:00 p.m. PDT (6:00 p.m. EDT)
APA # NR750
Improved Interpatient Pharmacokinetic Variability of Lisdexamfetamine Dimesylate Compared With Mixed Amphetamine Salts Extended Release (MAS XR) in Children Aged 6 to 12 Years With Attention-Deficit/Hyperactivity Disorder
May 23, 2007; 3:00 p.m. PDT (6:00 p.m. EDT)
About VYVANSE and ADDERALL XR
Tell your doctor about any heart conditions, including structural abnormalities, that you, your child, or a family member, may have. Inform your doctor immediately if you or your child develops symptoms that suggest heart problems, such as chest pain or fainting.
VYVANSE or Adderall XR should not be taken by patients who have advanced disease of the blood vessels (arteriosclerosis); symptomatic heart disease; moderate to severe high blood pressure; overactive thyroid gland (hyperthyroidism); known allergy or unusual reactions to drugs called sympathomimetic amines (for example, pseudoephedrine); seizures; glaucoma; a history of problems with alcohol or drugs; agitated states; taken a monoamine oxidase inhibitor (MAOI) within the last 14 days.
Tell your doctor before using, VYVANSE or Adderall XR if you or your child are being treated for or have symptoms of depression (sadness, worthlessness, or hopelessness) or bipolar disorder; have abnormal thoughts or visions, hear abnormal sounds, or have been diagnosed with psychosis; have had seizures or abnormal EEGs; have or have had high blood pressure; exhibit aggressive behavior or hostility. Tell your doctor immediately if any of these conditions or symptoms develop while using VYVANSE or Adderall XR.
Abuse of amphetamines may lead to dependence. Misuse of amphetamine may cause sudden death and serious cardiovascular adverse events. These events have also been reported rarely with amphetamine use.
VYVANSE and Adderall XR were generally well tolerated in clinical studies. The most common side effects in studies of Vyvanse included: children - difficulty falling asleep, stomachache, and irritability. The most common side effects in studies of Adderall XR included: children - decreased appetite, difficulty falling asleep, stomachache, and emotional lability; adolescents - loss of appetite, difficulty falling asleep, stomachache, and weight loss; adults - dry mouth, loss of appetite, difficulty falling asleep, headache, and weight loss.
Aggression, new abnormal thoughts/behaviors, mania, growth suppression, worsening of motion or verbal tics and Tourette's syndrome have been associated with use of drugs of this type. Tell your doctor if you or your child have blurred vision while taking VYVANSE or Adderall XR.
DAYTRANA should not be used in patients with allergy to methylphenidate or patch components; marked anxiety, tension and agitation; glaucoma; tics, diagnosis or a family history of Tourette's syndrome; seizures; 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; EEG abnormalities; bipolar disorder; depression. Growth and hematologic monitoring is advised during prolonged treatment. Patients should avoid applying external heat to the DAYTRANA patch. Skin irritation or contact sensitization may occur.
DAYTRANA should be given cautiously to patients with a history of drug dependence and alcoholism. Chronic abuse can lead to marked tolerance and psychological dependence. Frank psychotic episodes can occur, especially with parenteral abuse. Careful supervision is required during withdrawal from abusive use, since severe depression may occur. Withdrawal following chronic therapeutic use may unmask symptoms of the underlying disorder.
Common adverse events reported by patients who received DAYTRANA in clinical trials were decreased appetite, insomnia, nausea, vomiting, decreased weight, tics, affect lability, and anorexia, consistent with adverse events commonly associated with the use of methylphenidate.
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.