San Francisco, CA, May 21, 2003 – Shire Pharmaceuticals Group plc (NASDAQ: SHPGY, LSE: SHP.L, TSE: SHQ CN) announced results of a long-term clinical trial that showed significant improvements in symptom control and quality of life in children with attention-deficit/hyperactivity disorder (ADHD) with continued, long-term treatment (two-year) using a once-daily mixed salts amphetamine product. Moreover, these children sustained improvement in ADHD symptoms of at least 35 percent throughout the study. This information was presented today at the American Psychiatric Association (APA) annual meeting.
ADHD is the most commonly diagnosed psychiatric disorder in children and adolescents. Approximately two million U.S. children, three to seven percent of all school-aged children, have been diagnosed with ADHD. The disorder is characterized by symptoms of inattention, impulsiveness and hyperactive behavior.
"ADHD is an all-day disorder that requires treatment to manage symptoms at home, in school, and in socials settings. Our study shows that long-term treatment with a once-daily mixed salts amphetamine product remains effective in significantly controlling the symptoms of ADHD in children, which is very reassuring to health care providers and parents," said James McGough, M.D., associate professor, UCLA Neuropsychiatric Institute.
Long-Term Safety and Efficacy of Once-Daily Mixed Salts Amphetamine Product in Children With ADHD (APA Presentation Session #21) Prior to this two-year extension trial, 560 children had participated in one of two short-term clinical trials (three to four weeks) of the same medication. Results from the two-year study showed that, on average, the children achieved and maintained a significant improvement of at least 35 percent (compared to at the beginning of the study) in their ADHD symptoms during the two-year extension trial of the drug, based on an analysis using a standard and validated measure, the Conners' Global Index Scale-Parent Version (CGIS-P) scores.
The 10-item CGIS-P scale monitors treatment response and effectiveness. CGIS-P total scores range from zero to 30, which decline as ADHD symptoms are better controlled. The CGIS-P scores declined throughout the study from their initial-visit score average of 11.6 to 7.6 at 24 months and study conclusion (P< 0.001), indicating that these patients were able to control their symptoms over an extended period of time. This improvement in ADHD symptoms also was documented when patients were grouped based on their pre-extension study therapy.
Specifically, the 138 children who stopped taking the study medication between the short-term trials and enrollment in this long-term extension study (i.e., they were not receiving medication at the baseline visit for the long-term study) showed significant improvement (>35 percent) from their initial average CGIS-P score their final average score (P <0.001). The 182 patients who received a placebo during the short-term trials and then received the active drug in the extension study also experienced a decrease in average CGIS-P scores (>35 percent, P <0.001.) The 228 children already receiving the drug during the short-term clinical trials and during the extension trial maintained ADHD symptom control. This last subset had already experienced an average of at least 35 percent improvement in symptom control during the short-term pivotal clinical trial prior to enrolling in this two-year extension.
"Since ADHD is a condition that requires ongoing treatment, many parents are concerned that the medication may become less effective overtime, requiring higher doses or a change of medication to maintain optimal ADHD symptom control," said McGough. "The sustained improvement using the once daily mixed salts amphetamine product in controlling ADHD symptoms in this study should alleviate the fears of families and physicians that the once daily mixed salts amphetamine product may lose its effectiveness over time. This study documents a robust response which is maintained even when the drug is used in the long term."
The medication was generally well tolerated during the extension trial. The common side effects seen over the 24 months included headache, loss of appetite, insomnia, and abdominal pain. The majority of treatment-emergent side effects were mild and transient, with the majority occurring within the first three months of the extension study. No clinically significant changes in the patients' average heart rates or blood pressure measures occurred. Side effects were similar to those reported in previous short-term trials of the medication. Of the 560 enrollees, 273 (48 percent) completed the study, with only 84 (14.8 percent) withdrawing due to a side effect. The effectiveness of the once daily mixed salts amphetamine product for long-term use, i.e., for more than three weeks, has not been systematically evaluated in controlled trials. Data are inadequate to determine whether chronic use of stimulants in children, including amphetamine, may be causally associated with suppression of growth. At enrollment, the extension trial participants' average age was 8.7 years, 78 percent were boys, 73 percent were white, 12 percent were black, 9 percent were Hispanic and 6 percent had another ethnicity.
Long-Term Mixed Salts Amphetamine Product Treatment Improves Quality of Life in ADHD Children (APA Poster #650) Treatment with a once-daily a mixed salts amphetamine product also significantly enhanced the quality of life of children with ADHD and the improvement persisted during long-term treatment (up to two years), based on Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) scores. The scores were generated based on parents' perspectives and assessed patients' physical health, mood and family relationships as well as overall life satisfaction and contentment.
Specifically, the 560 children, aged 6 to 12 years, who participated in the two-year extension study averaged significantly greater Q-LES-Q scores at 12, 18 and 24 months (56, 57 and 56 points, respectively), compared to the average score at study start (49), P<0.00001 for each time point. A higher Q-LES-Q score indicates improvement in a patient's physical health, mood, family relationships and overall quality of life.
About ADHD
Approximately two million U.S. children, three to seven percent of all school-aged children, have been diagnosed with ADHD and as many as 66 percent may still exhibit symptoms into adulthood, according to the National Institute of Mental Health. ADHD is a significant mental health concern that impacts the patients, their families and their social circle. Children with ADHD often are inattentive, impulsive, and hyperactive – difficulties serious enough to interfere with their ability to function normally in home, academic or social settings. These symptoms continue beyond the school day, affecting all aspects of the child's life.
ADHD is a neurological brain 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. Hyperactivity is seen less frequently as the patient ages, although inattention and impulsivity often remain.
Although there is no "cure" for ADHD, physicians, parents, teachers, nurses and advocates are finding ways to help people with the condition learn to adapt to their academic, social and work settings. ADHD usually can be successfully managed with a combination of treatments, including educational approaches, psychological and behavioral therapies and medication. A recent clinical trial found that therapies that include carefully monitored medication are more effective than those that do not, such as behavioral therapy alone. Medication should be considered part of an overall multi-modal treatment plan for ADHD.
Shire Pharmaceuticals Group plc
Shire Pharmaceuticals Group plc (Shire) is a rapidly growing international emerging pharmaceutical company with a strategic focus on four therapeutic areas – central nervous system disorders (CNS), gastrointestinal (GI), oncology, and anti-infectives. Shire also has three platform technologies: advanced drug delivery, lead optimization for small molecules and Biologics. Shire's core strategy is based on research and development combined with in-licensing and a focus on eight key pharmaceutical markets.
The once-daily mixed salts amphetamine product is distributed in the United States by Shire US Inc., the sales and marketing subsidiary of Shire Pharmaceuticals, plc.
For further information on Shire, please visit the Company's website: www.shire.com; or www.adhdsupportcompany.com.
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 on Shire's Attention Deficit 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 date of lanthanum carbonate (FOSRENOL®) and METHYPATCH ® , and other risks and uncertainties detailed from time to time in our filings, including the Annual Report filed on Form 10-K by Shire with the Securities and Exchange Commission.
APA Presentations #21, Wednesday, May 21, 11:00 AM to 12:30 PM
"Long-Term Safety and Efficacy of Adderall XR in Children With ADHD." McGough, James, M.D.
APA Poster #650, Wednesday, May 21, 3:00 PM to 5:00 PM
"Long-Term Adderall Extended Release Treatment Improves Quality of Life in ADHD Children." Lopez, Frank A., M.D.
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