BioMarin Reports Statistically Significant Changes in Kuvan Responding PKU Patients

BioMarin Pharmaceutical Inc.

announced today results from the PKU-016 ASCEND study, the largest randomized controlled trial evaluating neuropsychiatric outcomes in phenylketonuria (PKU) patients treated with the approved drug Kuvan (sapropterin dihydrochloride). The study evaluated medically important symptoms similar to attention deficit hyperactivity disorder (ADHD) in PKU patients whose blood levels of phenylalanine (Phe) are reduced by Kuvan. The primary endpoint of the study was evaluated using an attention deficit hyperactivity rating scale (ADHD-RS), commonly used to evaluate symptoms of inattentiveness and hyperactivity. Kuvan improved the ADHD-RS (p=0.085), driven by a statistically significant change in the inattention component of the score (p=0.036). PKU patients have a lower degree of hyperactivity as compared to ADHD patients, which likely resulted in the less prominent benefits in this domain. The neurocognitive benefit of Kuvan in patients who respond to Kuvan was corroborated by the Behavior Rating Inventory of Executive Function, or BRIEF, in children who were rated by their parents.  Moderate to severe inattention deficit affected approximately one-third of patients in the study. Preliminary analysis of safety indicates that it is consistent with the general experience with Kuvan.  "We are encouraged to see the positive trend in the predetermined ADHD primary endpoint, which was driven by a statistically significant change in the sub-domain of inattentiveness," said Hank Fuchs, M.D., Chief Medical Officer of BioMarin. "We believe these results will provide useful information to the medical community on clinically relevant benefits of Kuvan and facilitate adoption of the product. Further, the results will help inform the design of the Phase 3 PEG-PAL program with key learnings about the measurement tools. We are encouraged by the results and plan to discuss the submission of this data with the FDA for possible inclusion in the Kuvan label." In addition to the ADHD-RS and BRIEF instruments, other exploratory tests in the PKU-016 study of neuropsychiatric deficit in PKU patients demonstrated a higher level of impairment in PKU patients than the normal population. Further analyses are underway to complete the evaluation of Kuvan on these outcome measures.