Phase III study presented at American Psychiatric Association Meeting
Shire Pharmaceuticals Group plc (NASDAQ: SHPGY, LSE: SHP.L, TSE: SHQ CN) announced that adults with attention-deficit/hyperactivity disorder (ADHD) experienced significant ADHD symptom control when treated with once-daily ADDERALL XR (a mixed salts amphetamine product). The 18-month interim analysis of a two-year Phase III trial led by Harvard investigators was discussed today during a platform presentation at the American Psychiatric Association (APA) annual meeting in New York City.
"Adults with ADHD can benefit from treatment with ADDERALL XR over the long-term because it can improve their ability to maintain focus, concentrate, and pay attention for longer periods of time, which may enable them to achieve more in professional, academic and social settings," said lead investigator Joseph Biederman, M.D., professor of psychiatry at Harvard Medical School.
Up to 65 percent of children with ADHD may still exhibit symptoms into adulthood and an estimated 4.4 percent of the U.S. adult populations are affected by ADHD. If left untreated, ADHD may seriously and adversely affect patients as well as their families, friends and coworkers. The disorder's symptoms of inattention and impulsivity, if untreated, can result in poor performance in the workplace and may increase adults' risk for other problems, such as drug abuse, anti-social behavior, and poor self-esteem, all of which can further impair social and family relationships, Biederman explained.
After these adult patients completed a four-week placebo-controlled trial with ADDERALL XR, they entered into a two-year extension study. The 18-month interim analysis of this extension study revealed that they maintained a significant reduction in their ADHD symptoms when treated with ADDERALL XR. For many patients, this sustained reduction in ADHD symptoms was at doses equivalent to those used in the initial four-week study, which reinforced previous findings that patients do not build up a tolerance to the effects of ADDERALL XR, says Biederman. ADDERALL XR was found to be significantlyefficacious across all doses.
Investigators measured patients' symptoms using a validated ADHD Rating Scale (ADHD-RS), in which scores are considered severe, moderate or mild. The ADHD-RS assesses the 18 individual items related to ADHD that are listed within in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Nine of these items assess inattentive symptoms and the other nine items assess hyperactive and impulsive symptoms. Sample rating categories include "avoids tasks that require sustained mental effort" and "talks excessively." Patients with more severe ADHD improved the most on ADDERALL XR treatment in the four-week placebo controlled study.
"When determining the most appropriate ADDERALL XR dose for an adult ADHD patient, physicians should optimize it for best symptom control and assure patients that once a stable dose of the medication is reached they are not very likely to require increased doses," said Dr Biederman. "Also, because the drug is well tolerated, physicians can reassure patients that most side effects are mild to moderate in severity, and usually occur in the first month of treatment. Patients are more likely to stay the course with their medication and yield its full therapeutic benefit when they understand their dosing and possible side effects."
After completion of the initial 4-week study, during which patients had significant improvements in ADHD symptoms within the first week, patients could opt to enroll in the long-term, 24-month, open-label extension study. All patients restarted ADDERALL XR at 20 mg/d. Then patients and physicians determined the optimal dose of ADDERALL XR (either 20, 40, 60 mg/day) through weekly visits, assessments of the severity of ADHD symptoms via the ADHD-RS, and dosage adjustments during the first part of the extension study. This dose optimization resulted in a average 45 percent reduction in total symptoms of ADHD in patients who had received placebo during the short-term controlled study. Patients who continuously received ADDERALL XR in both studies also experienced a significant decreased in total average symptom score.
An evaluation of the ADHD-RS Inattention subscale revealed that patients that switched from placebo to ADDERALL XR had a significant improvement, 43 percent reduction on average, in their symptom score. Likewise, an average 47 percent reduction in the ADHD-RS Hyperactive/Impulsive subscale was also noted for the same group of patients. Patients who continuously received the drug in both trials or those patients with interrupted ADDERALL XR treatment also experienced further improvement on both subscales.
Once optimized to the most effective dose of ADDERALL XR, few patients required dose adjustments for the duration of the long-term study. At six months, 14 percent of patients received 20 mg/d, 43 percent received 40 mg/d and 44 percent received 60 mg/d. At 18 months, slightly more patients received 60 mg/d (47 percent), and slightly fewer were receiving 40 mg/d (37 percent).
ADDERALL XR exhibited a good tolerability profile during both trials at all doses. The majority of side effects (95.9 percent)occurred in the first month of the trial, diminished over time and were generally mild or moderate in nature. The most frequently reported drug-related adverse events were common for this class of medications, and included dry mouth, loss of appetite, insomnia and headache.
The average age of participants was 40 and all had a history of ADHD before age 7. Of the participants, 60 percent were men and about 90 percent were Caucasian. Many of the participants were not diagnosed until they were adults and reported that their symptoms had negatively impacted their lives prior to treatment, indicating a public health need for earlier diagnosis and treatment, Biederman noted.
About ADDERALL XR
ADDERALLXR may not be right for everyone. ADDERALLXR was generally well tolerated in clinical studies. The most common side effects were decreased appetite, stomachache, difficulty falling asleep, and emotional lability. Patients should speak with their doctor if they have a history of high blood pressure or any heart conditions, glaucoma, thyroid problems, emotional instability, mental illness, or a known allergy to this type of medication. There is a potential for worsening of motion or verbal tics and Tourette's syndrome. Abuse of amphetamines may lead to dependence. A patient should report any new psychological symptoms to their physician. Please see accompanying full prescribing information.
ADHD is a neurobiological disorder that manifests as a persistent pattern of inattention and/or hyperactivity-impulsivity more frequent and severe than typically observed in individuals at a comparable level of development. Diagnosing ADHD in adults can help put many of their difficulties into perspective and help them better understand the reasons behind many lifelong symptoms. Proper diagnosis and effective treatment can help improve self-esteem, work performance and skills and social competencies.
Shire Pharmaceuticals Group plc
Shire Pharmaceuticals Group plc (Shire) is a global specialty pharmaceutical company with a strategic focus on meeting the needs of the specialist physician and currently focuses on developing projects and marketing products in the areas of central nervous system (CNS), gastrointestinal (GI), and renal diseases. Shire has operations in the world's key pharmaceutical markets (US, Canada, UK, France, Italy, Spain and Germany) as well as a specialist drug delivery unit in the US.
For further information on Shire, please visit the Company's Web site: 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 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 dates of lanthanum carbonate (FOSRENOL), METHYPATCH, XAGRID and the adult indication for ADDERALL XR, the implementation of the planned reorganization and other risks and uncertainties detailed from time to time in Shire's filings with the Securities and Exchange Commission.
APA Presentation # 106, Thursday, May 6, 2004, 11:00 AM to 12:30 PM
"Long-Term Safety and Efficacy of Mixed Amphetamine Salts Extended-Release for Adult ADHD." Biederman, Joseph, M.D.
Long-term study proves ADDERALL XR is a safe and effective option to treat adults with ADHD
Phase III study presented at American Psychiatric Association Meeting