Shire plc (LSE SHP, NASDAQ SHPGY), the global specialty biopharmaceutical company, announced that it has received approval from the US Food and Drug Administration (FDA) for INTUNIV(TM) (guanfacine) Extended Release Tablets for the treatment of AttentionDeficit/Hyperactivity Disorder (ADHD) in children and adolescents aged 6 to 17 years. INTUNIV, a oncedaily formulation of guanfacine, is the first selective alpha2A adrenergic receptor agonist approved for the treatment of ADHD. Although the mechanism of action is unknown, INTUNIV is thought to directly engage receptors found in the prefrontal cortex an area of the brain that has been linked in preclinical research to ADHD. Stimulation of the postsynaptic alpha2A receptors is thought to strengthen working memory, reduce susceptibility to distraction, improve attention regulation, improve behavioral inhibition, and enhance impulse control.

“Shire is proud to introduce INTUNIV, providing clinicians, patients, and their families with a novel ADHD treatment option,” said Mike Cola, President of Shire Specialty Pharmaceuticals. “This is a complex disorder in which patients may present with multiple symptoms and behaviors that can be disruptive. INTUNIV expands the Shire ADHD portfolio with a nonscheduled medication, allowing clinicians to optimize their overall approach toward managing ADHD and may help provide symptom control for children and teens with ADHD who often have difficulty responding appropriately to everyday situations and challenges.”

Oncedaily INTUNIV is expected to be available in US pharmacies in November and will come in four dosage strengths (1 mg, 2 mg, 3 mg, and 4 mg). INTUNIV will be 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.

“Everyday situations and challenges may be difficult for children and adolescents with ADHD as it is a disruptive disorder that includes symptoms and behaviors such as being easily distracted, always on the go, interrupting others, arguing with adults, or temper outbursts,” said Frank A. Lopez, MD, a neurodevelopmental pediatrician in private practice at Childrens Developmental Center in Winter Park, Florida. “In clinical trials, INTUNIV, a selective alpha2A receptor agonist, significantly reduced ADHD symptoms across a full day as measured by parents at 6 pm, 8 pm, and 6 am the next morning. This is important because children with ADHD require symptom control at home, school, and during after school activities.”

The introduction of INTUNIV is consistent with the strategy of Shire 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 two ADHD medicines available outside the United States.

INTUNIV Demonstrated Significant Reduction in ADHD Symptoms

The efficacy of INTUNIV in the treatment of ADHD was established in two, similarly designed, placebocontrolled clinical trials in children and adolescents aged 6 to 17 years who met Diagnostic and Statistical Manual of Mental DisordersIV (DSMIV(R)) criteria for ADHD. Statistically significant improvements were reported by investigators, parents, and teachers.

The first pivotal trial was a phase III, doubleblind, parallelgroup trial, in which investigators randomized 345 children aged 6 to 17 years to either a placebo or a fixed 2mg, 3mg, or 4mg dose of INTUNIV given once daily during an eightweek period. The second pivotal trial was a phase III, doubleblind, parallelgroup trial, in which investigators randomized 324 children aged 6 to 17 years to either a placebo or a fixed 1mg, 2mg, 3mg, or 4mg dose of INTUNIV given once daily during a nineweek 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 onceweekly basis using the clinician administered and scored ADHD Rating ScaleIV (ADHDRSIV), a scale frequently used in ADHD clinical trials that assesses hyperactive, impulsive, and inattentive symptoms. The primary outcome was the change in total ADHDRSIV scores from baseline to end point in both studies.

Both trials demonstrated statistically significant improvements in ADHDRSIV scores in patients taking INTUNIV beginning one to two weeks after patients began receiving oncedaily doses of INTUNIV. In the first pivotal trial, the mean reduction in ADHDRSIV total scores at end point were 16.7 for INTUNIV compared to 8.9 for placebo (P