Nicola Longo1, Komudi Siriwardena2, Annette Feigenbaum2, David Dimmock3, Barbara K Burton4, Sylvia Stockler5, Susan Waisbren6, William Lang7, Elaina Jurecki7, Charlie Zhang7, Suyash Prasad7. 1. Department of Medical Genetics, Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA. 2. Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada. 3. Medical College of Wisconsin, Milwaukee, Wisconsin, USA. 4. The Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA. 5. British Columbia Children's Hospital, Vancouver, British Columbia, Canada. 6. Boston Children's Hospital, Boston, Massachusetts, USA. 7. BioMarin Pharmaceutical, Inc., Novato, California, USA.
Abstract
PURPOSE: Sapropterin is an oral synthetic formulation of tetrahydrobiopterin prescribed as adjunctive therapy for phenylketonuria. The efficacy of sapropterin in reducing blood phenylalanine levels has been demonstrated in clinical studies of individuals with phenylketonuria older than 4 years of age. Its effect on neurocognitive functioning in younger children has not been examined. METHODS: A 2-year interim analysis of blood phenylalanine levels, prescribed dietary phenylalanine intake, and neurocognitive functioning was performed in children who started receiving sapropterin at 0-6 years of age and responded with a ≥30% mean blood phenylalanine reduction. Children were evaluated at baseline and 2-year follow-up. RESULTS: Sapropterin had a favorable safety profile and lowered blood phenylalanine levels with increased prescribed dietary phenylalanine intakes. Mean full-scale intelligence quotient was 103 ± 12 at baseline and 104 ± 10 at 2-year follow-up (P = 0.50, paired t-test, n = 25). For children younger than 30 months of age, the cognitive composite score from the Bayley Scales of Infant and Toddler Development, Third Edition, remained within the average range. CONCLUSION: Sapropterin had a favorable safety profile, was effective in lowering blood phenylalanine levels while clinically requiring dietary adjustment, resulting in increased phenylalanine intake, and preserved neurocognitive performance in children who started therapy between 0 and 6 years of age.
PURPOSE: Sapropterin is an oral synthetic formulation of tetrahydrobiopterin prescribed as adjunctive therapy for phenylketonuria. The efficacy of sapropterin in reducing blood phenylalanine levels has been demonstrated in clinical studies of individuals with phenylketonuria older than 4 years of age. Its effect on neurocognitive functioning in younger children has not been examined. METHODS: A 2-year interim analysis of blood phenylalanine levels, prescribed dietary phenylalanine intake, and neurocognitive functioning was performed in children who started receiving sapropterin at 0-6 years of age and responded with a ≥30% mean blood phenylalanine reduction. Children were evaluated at baseline and 2-year follow-up. RESULTS: Sapropterin had a favorable safety profile and lowered blood phenylalanine levels with increased prescribed dietary phenylalanine intakes. Mean full-scale intelligence quotient was 103 ± 12 at baseline and 104 ± 10 at 2-year follow-up (P = 0.50, paired t-test, n = 25). For children younger than 30 months of age, the cognitive composite score from the Bayley Scales of Infant and Toddler Development, Third Edition, remained within the average range. CONCLUSION: Sapropterin had a favorable safety profile, was effective in lowering blood phenylalanine levels while clinically requiring dietary adjustment, resulting in increased phenylalanine intake, and preserved neurocognitive performance in children who started therapy between 0 and 6 years of age.
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