US FDA approves attention deficit patch for children
The US Food and Drug Administration (FDA) has approved Shire's transdermal patch Daytrana for the treatment of attention deficit hyperactivity disorder (ADHD) in children six to 12 years of age, making it the first and only non-oral medication indicated for the treatment of ADHD.
Manufactured for Shire by Noven, Daytrana is a once-daily patch designed to be applied each morning to alternating hips and worn for nine hours. It contains the central nervous system (CNS) stimulant methylphenidate and is delivered through Noven's patented DOT Matrix transdermal technology, which is designed to provide consistent drug release throughout the day. Designed to stay on during the normal daily activities of a child - including swimming, exercising, and bathing - the patch will be available in 10 mg, 15 mg, 20 mg and 30 mg dosage strengths.
The three main symptoms of ADHD are inattention, hyperactivity, and impulsivity. It is linked to children who may have difficulty in school, troubled relationships with family and peers, and low self-esteem.. Considered the most commonly diagnosed psychiatric disorder in children and adolescents, it affects approximately 7.8% of all school-aged children, equating to more than four million in the US alone.
A phase II study in 79 children with ADHD showed a "statistically significant improvement over placebo on the measures tested". Behaviour, which was measured using the Swanson, Kotkin, Agler, M-Flynn, and Pelham-Deportment (SKAMP-D) scale, improved with Daytrana (mean score 3.2 for versus 8.0 for placebo) and at all time-points assessed up to and including 12 hours post-application (P < .01). The mean number of mathematics problems attempted by children taking Daytrana on the Permanent Product Measure of Performance (PERMP) scale was "significantly more" than those taking placebo (P <.0001). The number of correctly tackled problems was also higher in the Daytrana group.
A phase III naturalistic trial with 270 participants showed that when worn for nine hours the Daytrana patch reduced overall symptoms of ADHD, compared to a placebo (P < .0001), as measured by scores on the ADHD Rating Scale-IV (ADHD-RS IV). By the study's end, mean ADHD-RS-IV scores declined 56% from baseline for children treated with Daytrana against a decline of 25 % for those treated with placebo (P < .0001).
In both studies the drug was generally well tolerated during both the dose optimisation and double-blind phases. Adverse events were typically mild to moderate, resolved with continued therapy and consistent with known effects of methylphenidate. Common adverse events included decreased appetite, insomnia, nausea, vomiting, weight loss, tic, and affect lability (mood swings).
As part of the agreement between Shire and Noven for Daytrana, Shire completed an upfront payment to Noven of $25m in 2003 and may make separate milestone payments up to $125m; $50m of which will be paid following the FDA approval while the remaining $75m is conditioned upon the achievement of certain sales targets. The patch will be available in pharmacies in the US in mid-2006.