Dr. Robert Hendren, Professor and Vice Chair of Psychiatry and Director of Child and Adolescent Psychiatry at the University of California, San Francisco commented, "These data document what has been known by PKU clinicians for a long time; namely, mental health impairment is a prevalent and important problem affecting PKU patients and that improved control of their metabolic condition translates into improved control of the impairment in mental health."Abstracts will be submitted to the International Congress of Inborn Errors of Metabolism (ICIEM) and American Society of Human Genetics (ASHG) meetings this fall. Study Design PKU-016 is a double-blind, placebo-controlled, randomized study to evaluate the safety and therapeutic effects of Kuvan on neuropsychiatric symptoms in subjects with PKU. The study enrolled 206 patients, 118 of whom are responders to Kuvan as determined by a drop in blood Phe levels. The study includes a two-week screening period, a 13-week double-blind randomized treatment period and a 13-week open-label treatment period at a dose of 20 mg/kg/day. The Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS) is an instrument for assessing treatment response in patients who do not have metabolic disorders causing inattention and hyperactivity. The scale has been widely used to evaluate therapies approved for ADHD in patients without metabolic brain disease. Because inattention observed in PKU patients is similar in clinical presentation, the ADHD-RS was used to measure outcomes. The Behavior Rating Inventory of Executive Function (BRIEF) rating scale is an instrument to assess executive function behaviors. The 86-item questionnaire forms a Global Executive Composite, which is comprised of two indices: Behavioral Regulation and Metacognition and eight sub-domains exploring specific deficits in executive functioning.
|All patients (N)||108||98||Total= 206|
|Kuvan responders (N)||57||61||Total =118|
|ADHD-like Kuvan responders (N)||19||19||Total = 38|
|Change from baseline ADHD-RS||-5.4||-9.5||Difference = -4.1 (in favor of Kuvan) p=0.085, Kuvan versus placebo|
|Change from baseline inattentiveness domain||-2.6||-6.0||Difference -3.4 (in favor of Kuvan) p=0.036, Kuvan versus placebo|