Forschung & Innovation
Publikationen
Long-term safety of sapropterin in paediatric and adult individuals with phenylalanine hydroxylase deficiency
PMU Autor*in
Florian B Lagler
Alle Autor*innen
François Feillet, Jean-Baptiste Arnoux, María Bueno Delgado, Alberto Burlina, Brigitte Chabrol, Ece Kucuksayrac, Florian B Lagler, Ania C Muntau, David Olsson, Sabrina Paci, Frank Rutsch, Francjan J van Spronsen,
Fachzeitschrift
JOURNAL OF INHERITED METABOLIC DISEASE
Kurzfassung
Phenylketonuria is a rare inherited disorder that disrupts the metabolism of phenylalanine (Phe) to tyrosine by phenylalanine hydroxylase (PAH). Sapropterin dihydrochloride (Kuvan®) is approved for use in Europe to reduce blood Phe levels and improve Phe tolerance in sapropterin-responsive individuals. KAMPER (NCT01016392) is an observational, multinational registry assessing long-term safety and efficacy of sapropterin. Five hundred and seventy-six participants with PAH deficiency were enrolled from nine European countries (69 sites; December 2009-May 2016). Participants were aged <4 years (n = 11), 4 to <12 years (n = 329), 12 to <18 years (n = 141), and ≥18 years (n = 95) at enrolment. Overall, 401 (69.6%) participants experienced a total of 1960 adverse events; 61 events in 42 participants were serious, and two were considered sapropterin-related by the investigator. Mean (standard deviation) actual dietary Phe intake increased from baseline across all age groups: 957 (799) mg/day to a maximum of 1959 (1121) mg/day over a total study period of 11 years. Most participants exhibited an increase in Phe tolerance while blood Phe levels remained in the target range for their age (120-360 μmol/L for <12 years; 120-600 μmol/L for ≥12 years). Most participants exhibited normal growth for height, weight, and body mass index. No additional safety concerns were identified. As an observational study, limitations include variability in routine care practices and inconsistent availability of data. Long-term sapropterin use demonstrates a favourable safety profile in real-world settings and increases Phe tolerance in participants with PAH deficiency while maintaining blood Phe levels in the target ranges.
Keywords
Humans, Male, Middle Aged, Female, Europe, CHILD, ADOLESCENT, Registries, Child, Preschool, ADULT, Young Adult, Biopterins/analogs & derivatives, Phenylketonurias/drug therapy, Phenylalanine/blood, Phenylalanine Hydroxylase/deficiency