New Orleans – November 16, 2006 -- Shire plc (LSE: SHP, NASDAQ: SHPGY, TSX: SHQ) announced today that a single once-daily morning dose of the investigational amphetamine compound SPD465, extended release triple-bead mixed amphetamine salts, designed to reduce symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) in adults for up to 16 hours, was bioequivalent to a dose of ADDERALL XR (mixed salts of a single-entity amphetamine product) followed by a dose of mixed amphetamine salts immediate release ("MAS IR") eight hours later. The results of this phase I clinical trial in healthy adults were presented today at the 2006 U.S. Psychiatric & Mental Health Congress (USPMHC) annual meeting in New Orleans.
"Adults with ADHD are particularly challenged by a normal day's activities that often extend into the evening, and SPD465 offers the possibility of full-day symptom control," said Lenard A. Adler, M.D., director of the Adult ADHD Program in the Departments of Psychiatry and Neurology at New York University (NYU) School of Medicine and author of Scattered Minds: Hope and Help for Adults with ADHD (Putnam).
On July 21, 2006, Shire submitted a New Drug Application for SPD465, which is now under FDA review. If approved, SPD465 would be the first and only ADHD stimulant product designed to control inattention, hyperactivity and impulsivity in adults for up to 16 hours with one daily dose, thus potentially eliminating the need for augmenting a long-acting stimulant medication with a short-acting stimulant during the latter part of the day. More than nine million American adults currently exhibit symptoms of ADHD.
About the Study
In the study, investigators randomized 20 healthy adults (average age of 30 years), to either of two treatments, once-daily SPD465 37.5 mg or 25 mg ADDERALL XR followed by 12.5 mg of MAS IR administered eight hours later. The researchers dispensed the assigned medication regimen to the participants after an overnight fast and collected blood plasma samples before dosing; hourly thereafter through the first 10 hours after dosing; and then periodically for the next two and a half days. After a washout period of seven days, each participant was crossed over to receive the alternate treatment.
Bioequivalency of the two medication regimens is supported by the pharmacokinetic data collected for both d-amphetamine and l-amphetamine. Maximum plasma concentrations for both d-amphetamine and l-amphetamine were similar between the SPD465 group and the ADDERALL XR plus MAS IR group (50.3 ng/ML and 49.3 ng/mL, respectively). Both d-amphetamine and l-amphetamine were quantifiable in plasma at one hour after dosing in both treatment groups. Mean plasma concentration profiles of d-amphetamine and l-amphetamine were similar throughout the day and into the evening hours for both SPD465 and ADDERALL XR augmented with MAS IR.
No clinically meaningful differences occurred between the two study groups regarding adverse events. The reported adverse events were generally considered mild and resolved before study end, except one reported case of acne. The most frequently reported adverse events in the SPD465 group of healthy adults were hypervigilance, decreased appetite, headache, eye irritation, back pain, increased energy and anorexia.
ADHD is one of the most common psychiatric disorders in children and adolescents. Although many people tend to think of ADHD as a childhood problem, up to 80 percent of children with ADHD may exhibit symptoms into adolescence and up to 65 percent of children with ADHD may still exhibit symptoms into adulthood. In fact, ADHD affects approximately 9 million adults. 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. A diagnosis of Attention-Deficit Hyperactivity Disorder in adults (ADHD; DSM-IV) implies the presence of hyperactive-impulsive and/or inattentive symptoms that cause impairment and were present before the age of 7 years. The symptoms must cause clinically significant impairment, e.g., in social, academic, or occupational functioning, and be present in two or more settings, e.g., work (or school) and at home. The symptoms must not be better accounted for by another mental 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 Development Inc. supported the study.
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Notes to editors
SPD465, a single entity, mixed amphetamine salt formulation designed to provide extended release of medication with symptom control for up to 16 hours, is being studied for the treatment of ADHD in adults. The most common adverse events reported in the phase I study were hypervigilance, decreased appetite, headache, eye irritation, back pain, increased energy and anorexia.
About 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 develop symptoms that suggest heart problems, such as chest pain or fainting.
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 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 thought 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 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.
ADDERALL XR was generally well tolerated in clinical studies. The most common side effects in studies 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 ADDERALL XR.
Shire's strategic goal is to become the leading specialty pharmaceutical company that focuses on meeting the needs of the specialist physician. Shire focuses its business on central nervous system, gastrointestinal, general products and human genetic therapies. 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.
"SAFE HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995
Statements included herein that are not historical facts are forwarding-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 plc's ADHD franchise; government regulation and approval, including but not limited to the expected product approval dates of SPD503 (guanfacine extended release) (ADHD), SPD465, extended release triple-bead mixed amphetamine salts (ADHD), MESAVANCE (mesalamine) with MMX technology (SPD 476) (ulcerative colitis), ELAPRASE (idursulfase) (Hunter Syndrome) and NRP104 (lisdexamfetamine dimesylate) (ADHD), including its scheduling classification by the Drug Enforcement Administration in the United States; Shire's ability to secure new products for commercialization and/or development; and other risks and uncertainties detailed from time to time in Shire's and its predecessor registrant Shire Pharmaceuticals Group 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, 2005.
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