Hollywood, FL July 1, 2009 Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical company, today announced results from a Phase 3b study that found VYVANSE (lisdexamfetamine dimesylate) CII demonstrated significant efficacy at 14 hours after administration during a simulated workplace environment study in adults with Attention Deficit Hyperactivity Disorder (ADHD). VYVANSE is the first approved stimulant for adults with ADHD to be evaluated in this setting, and these data were presented today at the 49th annual New Clinical Drug Evaluation Unit meeting in Hollywood, FL. VYVANSE is currently approved by the US Food and Drug Administration (FDA) for the treatment of ADHD in children age 6 to 12 years and in adults with ADHD.
"Long-acting medication may be important for adults with ADHD because ADHD symptoms, such as inattention, hyperactivity, and impulsivity, may impact them at work, as well as in at least one other area of their life," said Matthew Brams, MD, study author and psychiatrist in private practice with Bayou City Research, Ltd in Houston. "In this study, adults taking VYVANSE demonstrated significant efficacy as measured by the Permanent Product Measure of Performance (PERMP), from two hours, the first time point measured, up to 14 hours following administration. Additionally, adults taking VYVANSE demonstrated significant ADHD symptom improvement, as measured by the ADHD Rating Scale (ADHD-RS) with adult prompts. These findings may be important for adults who require ADHD symptom management at work, at home, and in social settings."
In this study, investigators evaluated adults with ADHD in an adult simulated workplace environment setting. In this setting, adults engaged in tests and activities that require a level of attention needed in many workplace settings. The efficacy of VYVANSE was measured by PERMP, a validated, time sensitive, skill adjusted math test designed to evaluate an adult's ability to attend, initiate, and complete written seatwork. The PERMP was administered at intervals during the course of the simulated workplace environment day.
"This study provides important information for physicians about the effect of treatment with VYVANSE throughout the day in adults," said Michael Yasick, Senior Vice President of the ADHD Business Unit at Shire. "Shire is committed to providing effective treatments for adults with ADHD who need significant symptom improvement through the day and into the evening. We are proud to have evaluated VYVANSE in adults in this workplace-like environment."
The adult simulated workplace environment study supports the results of a previous phase 3 clinical trial in adults in which once-daily VYVANSE significantly improved ADHD symptoms of inattention, such as the ability to focus and organize, as well as hyperactivity and impulsivity. In this previous study, the most common adverse events (greater than or equal to 5 percent and twice placebo) were decreased appetite, dry mouth, insomnia, nausea, diarrhea, anxiety, and anorexia.
About the Adult Simulated Workplace Environment Study
This randomized, double-blind placebo-controlled, crossover study evaluated the efficacy and safety of three doses of VYVANSE, 30 mg, 50 mg, and 70 mg, compared to placebo in 142 adults with ADHD using the adult simulated workplace environment setting. A four-week, open-label phase to identify the optimal dose preceded the two-week double-blind phase in which efficacy was evaluated.
The primary efficacy measure of the study was the average of postdose PERMP total scores in adults taking VYVANSE compared to placebo. The key secondary efficacy measure was to assess the duration of efficacy of VYVANSE compared to placebo using PERMP; the PERMP total score is the sum of the number of math problems attempted (PERMP-A) plus the number of math problems answered correctly (PERMP-C) in a 10-minute session. Patients took the PERMP test one half hour before their first dosing and then at 2, 4, 8, 10, 12, and 14 hours after dosing at two visits (visits 5 and 6) during the double-blind crossover phase.
VYVANSE demonstrated significant improvement in the average total PERMP scores, 312.9 for the VYVANSE group compared to 289.5 for the placebo group; P< .0001. Also, at each postdose assessment from two hours to 14 hours, the VYVANSE group had significantly better average PERMP total scores than the placebo group, (P< .01 for all). At the first time point measured, two hours postdose, the average change from predose measurement in total PERMP scores for the VYVANSE group was 41.5 versus 22.5 for the placebo group; P< .001.
In addition to PERMP, the investigators measured the efficacy of VYVANSE using the ADHD-RS with adult prompts, which is a standardized test for assessing symptoms of ADHD and for assessing response to treatment. This scale, which contains 18 items, is based on the ADHD diagnostic criteria as defined in the APA's Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, a publication of the American Psychiatric Association. In this study, VYVANSE demonstrated a reduction (approximately 52 percent) from baseline in average ADHD-RS total scores in adults, from 37.2 at baseline to 18.1 at visits 5 and 6. Adult patients taking placebo also demonstrated a reduction (approximately 21 percent) in average ADHD-RS total scores, from 37.2 at baseline to 29.6 at visits 5 and 6.
The study also assessed the safety of VYVANSE, finding that the most frequently reported adverse events (greater than or equal to 5 percent) for patients during the dose-optimization phase were decreased appetite, dry mouth, headache, insomnia, upper respiratory tract infection, irritability, nausea, anxiety, and feeling jittery.
VYVANSE, which was introduced in the United States in July 2007 for the treatment of ADHD in children age 6 to 12 years and approved in April 2008 to treat ADHD in adults, is currently available in six dosage strengths of 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, and 70 mg. To date, more than 6 million VYVANSE prescriptions have been filled, bringing the current US market share to over 12 percent based on weekly branded prescription volume. Additionally, Shire has executed agreements with 10 of Shire's top 11 managed care organizations (MCOs) to cover VYVANSE in a preferred formulary position. Approximately 95 percent of prescriptions are approved by health plans at the national average copay of $34.00. These figures are comparable with other ADHD treatment options.
VYVANSE is a therapeutically inactive prodrug, in which d-amphetamine is covalently bonded to l-lysine, and after oral ingestion it is converted to pharmacologically active d-amphetamine. The conversion of VYVANSE to d-amphetamine is not affected by gastrointestinal pH and is unlikely to be affected by alterations in GI transit times.
|Contact: Matthew Cabrey (Shire North America)|