PHILADELPHIA November 9, 2009 Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical company, today announced the availability of INTUNIV (guanfacine) Extended Release Tablets in pharmacies across the United States for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children and adolescents ages 6 to 17. INTUNIV, a once-daily formulation of guanfacine, is the first and only nonscheduled alpha-2A receptor agonist approved for the treatment of ADHD. In clinical trials, INTUNIV provided significant efficacy across the spectrum of ADHD symptoms that can be disruptive, such as being easily distracted, interrupting others, running around excessively, arguing with adults, and losing temper.
"INTUNIV has been shown to improve a range of ADHD symptoms and provides prescribers and patients with another treatment option for this complex disorder," said Rakesh Jain, MD, MPH, Director of Psychopharmacology Research at R/D Clinical Research, Inc, in Lake Jackson, Texas. "In clinical studies, INTUNIV was shown to provide significant ADHD symptom improvement across a full day, as reported by parents at approximately 6 PM, 8 PM, and 6 AM the next morning. These findings suggest that INTUNIV may be an important treatment option for children and adolescents with ADHD who are faced with the complexities of the disorder, both at school and at home. Because of this, many clinicians such as myself, have been highly anticipating its availability."
The US Food and Drug Administration (FDA) approved INTUNIV on September 2, 2009. Once-daily INTUNIV is now available in US pharmacies in four dosage strengths (1 mg, 2 mg, 3 mg, and 4 mg) and is marketed in the United States by the existing Shire ADHD sales team of nearly 600 representatives. INTUNIV is not a controlled substance and has no known potential for abuse or dependence.
"INTUNIV is the newest ADHD treatment to receive FDA approval and the latest addition to the Shire ADHD portfolio. The availability of INTUNIV now allows physicians to prescribe the first and only nonscheduled alpha-2A receptor agonist indicated for the treatment of ADHD to help their patients manage a range of ADHD symptoms," said Michael Yasick, Senior Vice President of the ADHD Business Unit at Shire. "Shire is proud to provide physicians and the ADHD community with a novel treatment choice, which expands the range of available treatment options, allowing physicians to optimize the management of ADHD."
The commitment of Shire to making INTUNIV available for ADHD patients is consistent with the company's strategy to expand and diversify its ADHD portfolio, which now consists of four ADHD treatment options of scheduled and nonscheduled medicines in the United States and three medicines approved for the treatment of ADHD outside the United States.
The efficacy of INTUNIV in the treatment of ADHD was established in two, similarly designed, placebo-controlled clinical trials in children and adolescents aged 6 to 17 years who met Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria for ADHD. Statistically significant improvements were reported by investigators, parents, and teachers.
The first pivotal trial was a phase III, double-blind, parallel-group trial, in which investigators randomized 345 children aged 6 to 17 years to either a placebo or a fixed 2-mg, 3-mg, or 4-mg dose of INTUNIV given once daily during an eight-week period. The second pivotal trial was a phase III, double-blind, parallel-group trial, in which investigators randomized 324 children aged 6 to 17 years to either a placebo or a fixed 1-mg, 2-mg, 3-mg, or 4-mg dose of INTUNIV given once daily during a nine-week period, with the 1 mg assigned only to patients weighing less than 50 kg (110 lbs).
In both trials, doses were increased in increments of 1 mg per week, and investigators evaluated participants' signs and symptoms of ADHD on a once-weekly basis using the clinician administered and scored ADHD Rating Scale-IV (ADHD-RS-IV), a scale frequently used in ADHD clinical trials that assesses hyperactive, impulsive, and inattentive symptoms. The primary outcome was the change in total ADHD-RS-IV scores from baseline to end point in both studies.
Both trials demonstrated statistically significant improvements in ADHD-RS-IV scores in patients taking INTUNIV beginning one to two weeks after patients began receiving once-daily doses of INTUNIV. In the first pivotal trial, the mean reduction in ADHD-RS-IV total scores at end point were -16.7 for INTUNIV compared to -8.9 for placebo (P< .0001); the mean reduction in ADHD-RS-IV total scores in the second pivotal trial were -19.6 for INTUNIV and -12.2 for placebo (P=.0040). Placebo-adjusted LS mean changes from baseline were statistically significant for all INTUNIV doses in the randomized treatment groups in both studies.
Additional secondary efficacy outcome measures included the Conners' Parent Rating Scale-Revised: Short Form (CPRS-R) and the Conners' Teacher Rating Scale-Revised: Short Form (CTRS-R). CPRS-R and CTRS-R are comprehensive scales that use parent and teacher observer and self-report ratings to help assess ADHD symptoms and behaviors in children and adolescents. Among some of the symptoms measured were: inattentiveness/being easily distracted, running around or climbing excessively, arguing with adults, losing temper, and interrupting or intruding on others. Significant improvements in mean day total scores were seen on both scales: based on the CPRS-R, parents reported significant improvement across a full day (as measured at 6 PM, 8 PM, and 6 AM the next morning); based on the CTRS-R, which was used only in the first pivotal trial, teachers reported significant improvement throughout the school day (as measured at 10 AM and 2 PM).
Safety was also evaluated during these pivotal trials and safety data showed that adverse events reported by participants using INTUNIV were generally mild to moderate in severity. Treatment-related adverse events greater than 10 percent included somnolence (32 percent), headache (26 percent), fatigue (18 percent), upper abdominal pain (14 percent), and sedation (13 percent). Sedation-related, treatment emergent adverse events were among the most common and were usually transient and mild to moderate in severity. Small to modest changes in blood pressure, pulse rate, and ECG parameters were observed.
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