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Cited by 196Metabolism and Genetic DisordersAmino Acid Enzymes and MetabolismLysosomal Storage Disorders Research

Efficacy of sapropterin dihydrochloride in increasing phenylalanine tolerance in children with phenylketonuria: a phase III, randomized, double-blind, placebo-controlled study

Trefz, Friedrich K., Burton, Barbara K., Longo, Nicola, Casanova, Mercedes Martinez-Pardo, Gruskin, Daniel J., Dorenbaum, Alex, Kakkis, Emil D., Crombez, Eric A. +11 more·2009·The Journal of Pediatrics
DOI 10.1016/j.jpeds.2008.11.040
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Abstract

Objective To evaluate the ability of sapropterin dihydrochloride (pharmaceutical preparation of tetrahydrobiopterin) to increase phenylalanine (Phe) tolerance while maintaining adequate blood Phe control in 4- to 12-year-old children with phenylketonuria (PKU).Study design This international, double-blind, randomized, placebo-controlled study screened for sapropterin response among 90 enrolled subjects in Part 1. In Part 2, 46 responsive subjects with PKU were randomized (3:1) to sapropterin, 20 mg/kg/d, or placebo for 10 weeks while continuing on a Phe-restricted diet. After 3 weeks, a dietary Phe supplement was added every 2 weeks if Phe control was adequate.Results The mean (+/-SD) Phe supplement tolerated by the sapropterin group had increased significantly from the pretreatment amount (0 mg/kg/d) to 20.9 (+/-15.4) mg/kg/d (P < .001) at the last visit at which subjects had adequate blood Phe control (<360 micromol/L), up to week 10. Over the 10-week period, the placebo group tolerated only an additional 2.9 (+/-4.0) mg/kg/d Phe supplement; the mean difference from the sapropterin group (+/-SE) was 17.7 +/- 4.5 mg/kg/d (P < .001). No severe or serious related adverse events were observed.Conclusions Sapropterin is effective in increasing Phe tolerance while maintaining blood Phe control and has an acceptable safety profile in this population of children with PKU.

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  • Sapropterin is the first non-dietary FDA-approved synthetic BH4 for phenylketonuria and lowers blood phenylalanine by stabilizing and increasing PAH activity.

    “Sapropterin (Kuvan) is the first non-dietary, FDA-approved, synthetic form of BH4 for patients with phenylketonuria that is effective in lowering blood Phen levels by stabilizing and increasing PAH activity”

    From Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications (2013) · cites this paper as Trefz et al., 2009

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Authors
Trefz, F. K., Burton, B. K., Longo, N., Casanova, M. M.-P., Gruskin, D. J., Dorenbaum, A., Kakkis, E. D., Crombez, E. A., Grange, D. K., Harmatz, P., Lipson, M. H., Milanowski, A., Randolph, L. M., Vockley, J., Whitley, C. B., Wolff, J. A., Bebchuk, J., Christ-Schmidt, H., & Hennermann, J. B.
Affiliations
  • Kreiskliniken Reutlingen (DE)
  • Lurie Children's Hospital (US)
  • University of Utah (US)
  • Emory University (US)
  • BioMarin (United States) (US)
  • University of California, Los Angeles (US)
  • Washington University in St. Louis (US)
  • UCSF Benioff Children's Hospital (US)
  • Kaiser Permanente (US)
  • Instytut Matki i Dziecka (PL)
  • University of Southern California (US)
  • University of Pittsburgh (US)
  • University of Minnesota (US)
  • University of Wisconsin–Madison (US)
  • Statistics Collaborative (US)
  • Charité – Universitätsmedizin Berlin (DE)
Corresponding author
Trefz, Friedrich K.
ORCID
Venue
The Journal of Pediatrics
Publisher
Elsevier BV
Published
2009-05
Volume
154
Issue
5
Pages
700-707.e1
ISSN
0022-3476 (ISSN-L)
DOI
10.1016/j.jpeds.2008.11.040
OpenAlex
W2037047569
Cited by
196
References
37
Citations by year
2026: 6 · 2025: 6 · 2024: 8 · 2023: 11 · 2022: 7 · 2021: 8 · 2020: 3 · 2019: 13 · 2018: 11 · 2017: 10 · 2016: 5 · 2015: 19 · 2014: 9 · 2013: 11 · 2012: 21
FWCI
14.70
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • The Journal of Pediatrics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
Keywords
sapropterin dihydrochloride, phenylketonuria, phenylalanine tolerance, tetrahydrobiopterin, children, phenylalanine-restricted diet, drug safety and efficacy
MeSH terms
Algorithms, Biopterins, Child, Child, Preschool, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, Male, Phenylalanine, Phenylketonurias, Dietary Supplements

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