Journal of Inherited Metabolic Disease

, Volume 30, Issue 5, pp 700–707

The response of patients with phenylketonuria and elevated serum phenylalanine to treatment with oral sapropterin dihydrochloride (6R-tetrahydrobiopterin): a phase II, multicentre, open-label, screening study


    • Children’s Memorial HospitalNorthwestern University Feinberg School of Medicine
    • Children’s Memorial Hospital, Division of Genetics
  • D. K. Grange
    • St. Louis Children’s HospitalWashington School of Medicine
  • A. Milanowski
    • Instytut Matki i Dziecka
  • G. Vockley
    • Children’s Hospital of Pittsburgh
  • F. Feillet
    • Department of PediatricsHôpital d’Enfants
  • E. A. Crombez
    • David Geffen School of Medicine at UCLA
  • V. Abadie
    • Hôpital Necker — Enfants Malades Pediatrie Generale
  • C. O. Harding
    • Oregon Health & Science University
  • S. Cederbaum
    • UCLA Medical Center
  • D. Dobbelaere
    • CHRU de Lille — Hôpital Jeanne de Flandres
  • A. Smith
    • Pacific Data Designs
  • A. Dorenbaum
    • BioMarin Pharmaceutical Inc.
Original Article

DOI: 10.1007/s10545-007-0605-z

Cite this article as:
Burton, B.K., Grange, D.K., Milanowski, A. et al. J Inherit Metab Dis (2007) 30: 700. doi:10.1007/s10545-007-0605-z


This study aimed to evaluate the response to and safety of an 8-day course of sapropterin dihydrochloride (6R-tetrahydrobiopterin or 6R-BH4) 10 mg/kg per day in patients with phenylketonuria (PKU), who have elevated blood phenylalanine (Phe) levels, and to identify a suitable cohort of patients who would respond to sapropterin dihydrochloride treatment with a reduction in blood Phe level. Eligible patients were aged ≥ 8 years, had blood Phe levels ≥ 450 μmol/L and were not adhering to a Phe-restricted diet. Suitable patients were identified by a ≥30% reduction in blood Phe level from baseline to day 8 following sapropterin dihydrochloride treatment. The proportion of patients who met these criteria was calculated for the overall population and by baseline Phe level (<600, 600 to <900, 900 to <1200 and ≥1200 μmol/L). In total, 485/490 patients completed the study and 20% (96/485) were identified as patients who would respond to sapropterin dihydrochloride. A reduction in Phe level was observed in all subgroups, although response was greater in patients with lower baseline Phe levels. Wide variability in response was seen across all baseline Phe subgroups. The majority of adverse events were mild and all resolved without complications. Sapropterin dihydrochloride was well tolerated and reduced blood Phe levels across all PKU phenotypes tested. Variability in reduction of Phe indicates that the response to sapropterin dihydrochloride cannot be predicted by baseline Phe level.

Copyright information

© SSIEM and Springer 2007